{"id":"asparaginase","rwe":[],"_fda":{"id":"cca29ff5-d000-43da-b64a-c65816a8a9c4","set_id":"857e53aa-1098-4dad-b654-0276cdd43e03","openfda":{"nui":["M0001815","N0000175669"],"unii":["G4FQ3CKY5R"],"route":["INTRAMUSCULAR"],"rxcui":["2561251","2561256"],"spl_id":["cca29ff5-d000-43da-b64a-c65816a8a9c4"],"brand_name":["Rylaze"],"spl_set_id":["857e53aa-1098-4dad-b654-0276cdd43e03"],"package_ndc":["68727-900-01","68727-900-03"],"product_ndc":["68727-900"],"generic_name":["ASPARAGINASE ERWINIA CHRYSANTHEMI (RECOMBINANT)-RYWN"],"product_type":["HUMAN PRESCRIPTION DRUG"],"pharm_class_cs":["Asparaginase [CS]"],"substance_name":["ASPARAGINASE"],"pharm_class_epc":["Asparagine-specific Enzyme [EPC]"],"manufacturer_name":["Jazz Pharmaceuticals, Inc."],"application_number":["BLA761179"],"is_original_packager":[true]},"version":"7","pregnancy":["8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, RYLAZE can cause fetal harm when administered to a pregnant woman. There are no available data on RYLAZE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproductive and developmental toxicity studies, intramuscular administration of asparaginase Erwinia chrysanthemi to pregnant rats and rabbits during organogenesis resulted in structural abnormalities and embryo-fetal mortality ( see Data ) at exposures below those in patients at the recommended human dose. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal Data Animal reproductive and developmental toxicity studies have not been conducted with RYLAZE. In embryofetal development studies, asparaginase Erwinia chrysanthemi was administered intramuscularly every other day during the period of organogenesis to pregnant rats (at 3, 6, or 12 mg/m 2 ) and rabbits (at 0.12, 0.30, or 0.48 mg/m 2 ). In rats given 12 mg/m 2 (approximately 0.48 times the maximum recommended human dose), maternal toxicity of decreased body weight gain was observed, as was a fetal finding of increased incidence of partially undescended thymic tissue. In rabbits, maternal toxicity consisting of decreased body weight was observed at 0.48 mg/m 2 (approximately 0.02 times the maximum recommended human dose). Increased post-implantation loss, a decrease in the number of live fetuses, and gross abnormalities (e.g., absent kidney, absent accessory lung lobe, additional subclavian artery, and delayed ossification) were observed at doses of ≥ 0.12 mg/m 2 (approximately 0.005 times the maximum recommended human dose)."],"description":["11 DESCRIPTION Asparaginase erwinia chrysanthemi (recombinant)-rywn contains an asparagine specific bacterial enzyme (L-asparaginase). L-asparaginase is a tetrameric enzyme that consists of four identical 35 kDa subunits with a combined molecular weight of 140 kDa. The amino acid sequence is identical to native asparaginase Erwinia chrysanthemi (also known as crisantaspase). The activity of asparaginase erwinia chrysanthemi (recombinant)-rywn is expressed in units, defined as the amount of enzyme that catalyzes the conversion of 1μmol of L-asparagine per reaction minute, per mg of protein. Asparaginase erwinia chrysanthemi (recombinant)-rywn is produced by fermentation of a genetically engineered Pseudomonas fluorescens bacterium containing the DNA which encodes for asparaginase Erwinia chrysanthemi . RYLAZE (asparaginase erwinia chrysanthemi (recombinant)-rywn) injection is supplied as a sterile, clear to opalescent, colorless to slightly yellow, preservative-free solution for intramuscular injection. Each 0.5 mL contains 10 mg asparaginase erwinia chrysanthemi (recombinant)-rywn and the inactive ingredients: polysorbate 80 (0.1 mg), sodium chloride (1.5 mg), sodium phosphate dibasic anhydrous (0.8 mg), sodium phosphate monobasic monohydrate (0.6 mg), and trehalose dihydrate (32.1 mg). Sodium hydroxide may be added during manufacture to adjust the pH. The pH is approximately 7."],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING RYLAZE (asparaginase erwinia chrysanthemi (recombinant)-rywn) injection is supplied as a sterile, clear to opalescent, colorless to slightly yellow, preservative-free solution in single-dose vials. Each single-dose vial (NDC 68727-900-01) contains 10 mg/0.5 mL asparaginase erwinia chrysanthemi (recombinant)-rywn. Each carton of RYLAZE (NDC 68727-900-03) contains 3 single-dose vials. Store RYLAZE vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not shake or freeze."],"geriatric_use":["8.5 Geriatric Use Clinical studies of RYLAZE did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients."],"pediatric_use":["8.4 Pediatric Use The safety and effectiveness of RYLAZE in the treatment of ALL and LBL have been established in pediatric patients 1 month to < 17 years who have developed hypersensitivity to a long-acting E. coli -derived asparaginase. Use of RYLAZE in these age groups is supported by evidence from an adequate and well-controlled study in adults and pediatric patients. The trial included 139 pediatric patients, including 2 infants (1 month to < 2 years), 99 children (2 years to < 12 years old), and 38 adolescents (12 years to < 17 years old). There were no clinically meaningful differences in safety or nadir serum asparaginase activity across age groups. The safety and effectiveness of RYLAZE have not been established in pediatric patients younger than 1 month of age."],"effective_time":"20250701","clinical_studies":["14 CLINICAL STUDIES The efficacy of RYLAZE for the treatment of patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) who have developed hypersensitivity to E. coli -derived asparaginase as a component of a multi-agent chemotherapeutic regimen was evaluated in Study JZP458-201 (NCT04145531), an open-label, multi-cohort, multi-center trial. In this trial, RYLAZE was administered at various dosages and routes of administration every Monday, Wednesday, and Friday for a total of 6 doses to replace each dose of pegaspargase. For the 225 evaluable patients, the median age was 10 years (range: 1-25 years); 61% were male and 39% were female; 69% were White, 11% were Black/African American, 4% were Asian, and 16% were of other or unknown race: 187 (83%) patients had experienced a hypersensitivity reaction (Grade ≥ 3) to pegaspargase, and 15 patients (7%) reported silent inactivation. The determination of efficacy was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL by simulation. Table 5 shows the proportion with NSAA ≥ 0.1 U/mL for each approved dosage regimen based on simulation in a virtual population [see Clinical Pharmacology ( 12.3 )] . Table 5: Proportion (95% CI) with NSAA ≥ 0.1 U/mL by Simulation RYLAZE Dosage Trough Sampling Time Proportion with NSAA > 0.1 U/mL (95% CI) a 25 mg/m 2 intramuscularly every 48 hours 48 hours 96.0 (94.4, 97.2) 25/25/50 mg/m 2 intramuscularly Monday morning/Wednesday morning/Friday afternoon Friday afternoon: 58 hours after 25 mg/m 2 Wednesday morning dose b 91.6 (90.4, 92.8) Monday morning: 67 hours after 50 mg/m 2 Friday afternoon dose c 91.4 (90.1, 92.6) a Based on 2,000 virtual subjects. b Based on maximum interval of 58 hours between the Wednesday morning and Friday afternoon doses. c Based on maximum interval of 67 hours between the Friday afternoon and Monday morning doses."],"pharmacodynamics":["12.2 Pharmacodynamics Asparaginase erwinia chrysanthemi (recombinant)-rywn exposure-response relationships and the time course of pharmacodynamic response are unknown."],"pharmacokinetics":["12.3 Pharmacokinetics The pharmacokinetic parameters of asparaginase erwinia chrysanthemi (recombinant)-rywn are presented based on serum asparaginase activity (SAA) after administration of RYLAZE in pediatric and young adult patients with ALL or LBL, unless otherwise specified. Asparaginase erwinia chrysanthemi (recombinant)-rywn maximum SAA (C max ) and area under the SAA-time curve (AUC) increase proportionally over a dosage range from 12.5 to 50 mg/m 2 (0.25 to 1 times the maximum approved recommended dose of 50 mg/m 2 ). The simulated exposures for asparaginase erwinia chrysanthemi (recombinant)-rywn after administration of the approved recommended dosages in a virtual population are summarized in Table 4. Table 4: Simulated RYLAZE Pharmacokinetic Parameters Based on SAA PK Parameter Geometric Mean (%CV) After Last Dose 25 mg/m 2 Intramuscularly Every 48 Hours 25/25/50 mg/m 2 Intramuscularly Monday, Wednesday, Friday Last 25 mg/m 2 Wednesday morning dose Last 50 mg/m 2 Friday afternoon dose C max (U/mL) 2.3 (55%) 2.3 (54%) 4.1 (57%) C trough (U/mL) 0.46 (75%) 0.3 (75%) a 0.39 (87%) b a C trough at maximum interval of 58 hours after the last 25 mg/m 2 Wednesday morning dose. b C trough at maximum interval of 67 hours after the last 50 mg/m 2 Friday afternoon dose. Absorption The median (min, max) T max of asparaginase erwinia chrysanthemi (recombinant)-rywn after intramuscular administration is 12 (8, 24) hours. The mean absolute bioavailability after intramuscular administration is 37% in healthy subjects. Distribution The geometric mean (%CV) volume of distribution of asparaginase erwinia chrysanthemi (recombinant)-rywn is 1.37 L/m 2 (47%). Elimination The geometric mean (%CV) clearance of asparaginase erwinia chrysanthemi (recombinant)-rywn is 0.17 L/hour/m 2 (42%) and the apparent half-life is 15.9 (11%) hours. Metabolism Asparaginase erwinia chrysanthemi (recombinant)-rywn is expected to be metabolized into small peptides by catabolic pathways. Specific Populations There were no clinically significant differences in the pharmacokinetics of asparaginase erwinia chrysanthemi (recombinant)-rywn based on age (1.4 to 25 years), weight (9 to 131 kg), or sex after the dose was adjusted by body surface area (BSA). The effect of renal and hepatic impairment on the pharmacokinetics of asparaginase erwinia chrysanthemi (recombinant)-rywn has not been studied. Body Surface Area The volume of distribution and clearance of asparaginase erwinia chrysanthemi (recombinant)-rywn increase with increasing BSA (0.44 to 2.53 m 2 ). Racial and Ethnic Groups Black or African American patients had 29% lower clearance which may increase SAA exposure compared to White and Asian patients. There were no clinically significant differences in clearance between Hispanic and Non-Hispanic patients."],"adverse_reactions":["6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in greater detail in other sections of the labeling: • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] • Pancreatic Toxicity [see Warnings and Precautions ( 5.2 )] • Thrombosis [see Warnings and Precautions ( 5.3 )] • Hemorrhage [see Warnings and Precautions ( 5.4 )] • Hepatotoxicity, including VOD [see Warnings and Precautions ( 5.5 )] Most common adverse reactions (incidence > 20%) are abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals Ireland Limited at 1-800-520-5568 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of RYLAZE described in the WARNINGS AND PRECAUTIONS reflect exposure in 167 patients administered RYLAZE intramuscularly at various dosages when used in combination with chemotherapy in study JZP458-201 [see Clinical Studies ( 14 )] . These patients received a median of 4 courses of RYLAZE (range: 1-15 courses); 65% of patients received at least four courses. The safety of RYLAZE described below and in Table 3 was evaluated in study JZP458-201, a multi-cohort study. Patients received RYLAZE administered intramuscularly at dosages of 25 mg/m 2 on Monday, Wednesday, and Friday or 25 mg/m 2 on Monday and Wednesday, and 50 mg/m 2 on Friday, for 6 doses as a replacement for a single dose of pegaspargase as a component of multi-agent chemotherapy [see Clinical Studies ( 14 )] . The patients had a median age of 11 years (range: 1‑25 years); the majority of patients were male (57%) and White (68%). The patients received a median of 4 courses of RYLAZE (range: 1-14 courses); 65% of patients received at least four courses. A fatal adverse reaction (infection) occurred in 1 patient treated with the RYLAZE 25/25/25 mg/m 2 dosage. Serious adverse reactions occurred in 60% of patients who received the recommended dosages of RYLAZE. The most frequent nonhematological serious adverse reactions (in ≥ 5% of patients) were febrile neutropenia, infection, drug hypersensitivity, pyrexia, nausea, dehydration, stomatitis, acute kidney injury, pancreatitis, diarrhea, and viral infection. Permanent discontinuation due to an adverse reaction occurred in 10% of patients who received RYLAZE intramuscularly at the recommended dosages. Adverse reactions resulting in permanent discontinuation included pancreatitis (5%), drug hypersensitivity (4%), and infection (1%). All patients treated with the recommended dosages of RYLAZE as a component of multi-agent chemotherapy experienced neutropenia, anemia, or thrombocytopenia. The most common nonhematological adverse reactions (incidence > 20%) in patients were abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia. Table 3 shows the common adverse reactions occurring in at least 15% of the patients. Table 3: Adverse Reactions (≥ 15% Incidence) in Patients Receiving RYLAZE as a Component of Multi-Agent Chemotherapy in Study JZP458-201 Adverse Reaction RYLAZE 25/25/25 mg/m 2 Intramuscular Dosage a (N = 33) RYLAZE 25/25/50 mg/m 2 Intramuscular Dosage a (N = 51) All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%) Abnormal liver test* # 70 18 75 27 Musculoskeletal pain* 45 6 35 4 Nausea* 45 9 47 8 Fatigue* 36 18 22 18 Headache 36 0 22 0 Infection* b 36 15 27 17 Febrile neutropenia 30 30 27 27 Pyrexia 30 6 20 0 Hemorrhage* 24 0 27 6 Stomatitis 24 12 27 4 Abdominal pain* 21 0 25 2 Decreased appetite 21 6 27 6 Drug hypersensitivity* 21 6 24 2 Hyperglycemia 21 3 12 4 Diarrhea* 18 6 25 4 Tachycardia* 18 0 16 2 Cough 15 0 14 0 Dehydration 15 9 12 6 Insomnia 15 0 4 0 Peripheral neuropathy* 15 0 6 0 Pancreatitis* # 12 0 22 10 Hypokalemia 9 3 22 8 * Includes grouped terms: Abnormal liver test : alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, transaminases increased; Musculoskeletal pain : arthralgia, back pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, pain in extremity; Nausea : nausea, vomiting; Fatigue : fatigue, asthenia; Infection : sepsis, upper respiratory tract infection, enterocolitis infectious, skin infection, bacteremia, paronychia, pneumonia, otitis externa, soft tissue infection, abdominal infection, conjunctivitis, device related infection, folliculitis, lymph gland infection, necrotizing fasciitis, perirectal abscess, peritonsillar abscess, sinusitis, subcutaneous abscess, wound infection; Drug hypersensitivity : drug hypersensitivity, rash, infusion related reaction, lip swelling, periorbital edema, throat irritation, urticaria, dry skin, eczema, erythema, hand dermatitis, rash maculo-papular, rash papular; Hemorrhage : contusion, epistaxis, catheter site hemorrhage, petechiae, hematochezia, menorrhagia, mouth hemorrhage, increased tendency to bruise, rectal hemorrhage; Abdominal pain : abdominal pain, abdominal pain upper; Diarrhea : diarrhea, colitis; Tachycardia : sinus tachycardia, tachycardia; Peripheral neuropathy : peripheral motor neuropathy, neuropathy peripheral, peripheral sensory neuropathy; Pancreatitis : pancreatitis, pancreatitis acute, amylase increased, lipase increased. *Includes adverse event terms and laboratory abnormalities Grading is based on Common Terminology Criteria for Adverse Events version 5.0. a RYLAZE was administered as a component of multi-agent chemotherapy regimens on a Monday, Wednesday, and Friday schedule. b Does not include the following fatal adverse reactions: infection (N=1). Clinically relevant adverse reactions in < 15% of patients who received RYLAZE in combination with chemotherapy included: Gastrointestinal disorders : Abdominal discomfort, abdominal distension, constipation, gastritis General disorders and administration site conditions : Infusion site reaction, injection site reaction, pain Infections and infestations : Viral infection, bacterial infection, fungal infection Investigations : Antithrombin III decreased, blood cholesterol increased, blood fibrinogen decreased, activated partial thromboplastin time prolonged Metabolism and nutrition disorders : Acidosis, hyperammonemia, hyperphosphatemia, hypertriglyceridemia, hypoglycemia Musculoskeletal and connective tissue disorders : Bone pain, muscular weakness, muscle spasms Nervous system disorders : Paresthesia, dizziness, gait disturbance, hyperammonemic encephalopathy Psychiatric disorders : Agitation, anxiety, irritability Respiratory, thoracic, and mediastinal disorders: Acute respiratory distress syndrome, pulmonary edema Renal and urinary disorders : Acute kidney injury Skin and subcutaneous disorders : Pruritus Vascular disorders : Hypertension, hypotension, thrombosis 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of RYLAZE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Hepatic: Veno-occlusive disease (VOD)"],"contraindications":["4 CONTRAINDICATIONS RYLAZE is contraindicated in patients with: • History of serious hypersensitivity reactions to Erwinia asparaginase , including anaphylaxis [see Warnings and Precautions ( 5.1 )] ; • History of serious pancreatitis during previous asparaginase therapy [see Warnings and Precautions ( 5.2 )] ; • History of serious thrombosis during previous asparaginase therapy [see Warnings and Precautions ( 5.3 )] ; • History of serious hemorrhagic events during previous asparaginase therapy [see Warnings and Precautions ( 5.4 )] ; • Severe hepatic impairment [ see Warnings and Precautions ( 5.5 ) ]. RYLAZE is contraindicated in patients with: • History of serious hypersensitivity reactions to RYLAZE, including anaphylaxis. ( 4 ) • History of serious pancreatitis during previous L-asparaginase therapy. ( 4 ) • History of serious thrombosis during previous L-asparaginase therapy. ( 4 ) • History of serious hemorrhagic events during previous L-asparaginase therapy. ( 4 ) • Severe hepatic impairment. ( 4 )"],"mechanism_of_action":["12.1 Mechanism of Action Asparaginase erwinia chrysanthemi (recombinant)-rywn is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The pharmacological effect of RYLAZE is based on the killing of leukemic cells due to depletion of plasma asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Asparaginase erwinia chrysanthemi (recombinant)-rywn is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The pharmacological effect of RYLAZE is based on the killing of leukemic cells due to depletion of plasma asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival. 12.2 Pharmacodynamics Asparaginase erwinia chrysanthemi (recombinant)-rywn exposure-response relationships and the time course of pharmacodynamic response are unknown. 12.3 Pharmacokinetics The pharmacokinetic parameters of asparaginase erwinia chrysanthemi (recombinant)-rywn are presented based on serum asparaginase activity (SAA) after administration of RYLAZE in pediatric and young adult patients with ALL or LBL, unless otherwise specified. Asparaginase erwinia chrysanthemi (recombinant)-rywn maximum SAA (C max ) and area under the SAA-time curve (AUC) increase proportionally over a dosage range from 12.5 to 50 mg/m 2 (0.25 to 1 times the maximum approved recommended dose of 50 mg/m 2 ). The simulated exposures for asparaginase erwinia chrysanthemi (recombinant)-rywn after administration of the approved recommended dosages in a virtual population are summarized in Table 4. Table 4: Simulated RYLAZE Pharmacokinetic Parameters Based on SAA PK Parameter Geometric Mean (%CV) After Last Dose 25 mg/m 2 Intramuscularly Every 48 Hours 25/25/50 mg/m 2 Intramuscularly Monday, Wednesday, Friday Last 25 mg/m 2 Wednesday morning dose Last 50 mg/m 2 Friday afternoon dose C max (U/mL) 2.3 (55%) 2.3 (54%) 4.1 (57%) C trough (U/mL) 0.46 (75%) 0.3 (75%) a 0.39 (87%) b a C trough at maximum interval of 58 hours after the last 25 mg/m 2 Wednesday morning dose. b C trough at maximum interval of 67 hours after the last 50 mg/m 2 Friday afternoon dose. Absorption The median (min, max) T max of asparaginase erwinia chrysanthemi (recombinant)-rywn after intramuscular administration is 12 (8, 24) hours. The mean absolute bioavailability after intramuscular administration is 37% in healthy subjects. Distribution The geometric mean (%CV) volume of distribution of asparaginase erwinia chrysanthemi (recombinant)-rywn is 1.37 L/m 2 (47%). Elimination The geometric mean (%CV) clearance of asparaginase erwinia chrysanthemi (recombinant)-rywn is 0.17 L/hour/m 2 (42%) and the apparent half-life is 15.9 (11%) hours. Metabolism Asparaginase erwinia chrysanthemi (recombinant)-rywn is expected to be metabolized into small peptides by catabolic pathways. Specific Populations There were no clinically significant differences in the pharmacokinetics of asparaginase erwinia chrysanthemi (recombinant)-rywn based on age (1.4 to 25 years), weight (9 to 131 kg), or sex after the dose was adjusted by body surface area (BSA). The effect of renal and hepatic impairment on the pharmacokinetics of asparaginase erwinia chrysanthemi (recombinant)-rywn has not been studied. Body Surface Area The volume of distribution and clearance of asparaginase erwinia chrysanthemi (recombinant)-rywn increase with increasing BSA (0.44 to 2.53 m 2 ). Racial and Ethnic Groups Black or African American patients had 29% lower clearance which may increase SAA exposure compared to White and Asian patients. There were no clinically significant differences in clearance between Hispanic and Non-Hispanic patients. 12.6 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti‑drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of RYLAZE or of other asparaginase erwinia chrysanthemi (recombinant) products. During treatment in Study JZP458-201 (range 1 to 15 courses), 78/166 (47%) of patients treated with RYLAZE intramuscularly developed anti-asparaginase erwinia chrysanthemi (recombinant)-rywn antibodies. The effects of anti-drug antibodies on pharmacokinetics, pharmacodynamics, and effectiveness have not been adequately characterized."],"indications_and_usage":["1 INDICATIONS AND USAGE RYLAZE is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli -derived asparaginase. RYLAZE is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli -derived asparaginase. ( 1 )"],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS • Hypersensitivity: Monitor for signs or symptoms. Discontinue RYLAZE for serious reaction. ( 5.1 ) • Pancreatitis: Monitor for symptoms. Discontinue if pancreatitis occurs. ( 5.2 ) • Thrombosis: Discontinue RYLAZE for severe or life-threatening thrombosis. Provide anticoagulation therapy as indicated. ( 5.3 ) • Hemorrhage: Discontinue RYLAZE for severe or life-threatening hemorrhage. ( 5.4 ) • Hepatotoxicity, including hepatic veno-occlusive disease: Discontinue RYLAZE for grade 4 increases of bilirubin. ( 5.5 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions after the use of RYLAZE occurred in 29% of patients in clinical trials, and it was severe in 6% of patients [see Adverse Reactions ( 6.1 )] . Anaphylaxis was observed in 2% of patients after intramuscular administration. Discontinuation of RYLAZE due to hypersensitivity reactions occurred in 5% of patients. Hypersensitivity reactions were higher in patients who received intravenous asparaginase erwinia chrysanthemi (recombinant)-rywn. The intravenous route of administration is not approved. In patients administered RYLAZE intramuscularly in clinical trials, the median number of doses of RYLAZE that patients received prior to the onset of the first hypersensitivity reaction was 12 doses (range: 1-64 doses). The most commonly observed reaction was rash (19%), and 1 patient (1%) experienced a severe rash. Hypersensitivity reactions observed with L-asparaginase class products include angioedema, urticaria, lip swelling, eye swelling, rash or erythema, blood pressure decreased, bronchospasm, dyspnea, and pruritus. Premedicate patients prior to administration of RYLAZE as recommended [see Dosage and Administration ( 2.2 )] . Because of the risk of serious allergic reactions (e.g., life-threatening anaphylaxis), administer RYLAZE in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g., epinephrine, oxygen, intravenous steroids, antihistamines) [see Dosage and Administration ( 2.3 )] . Discontinue RYLAZE in patients with serious hypersensitivity reactions [see Dosage and Administration ( 2.3 )] . 5.2 Pancreatitis Pancreatitis, including elevated amylase or lipase, was reported in 20% of patients in clinical trials of RYLAZE and was severe in 8% [see Adverse Reactions ( 6.1 )] . Symptomatic pancreatitis occurred in 7% of patients, and it was severe in 6% of patients. Elevated amylase or lipase without symptomatic pancreatitis was observed in 13% of patients treated with RYLAZE. Hemorrhagic or necrotizing pancreatitis have been reported with L-asparaginase class products. Inform patients of the signs and symptoms of pancreatitis, which, if left untreated, could be fatal. Evaluate patients with symptoms compatible with pancreatitis to establish a diagnosis. Assess serum amylase and lipase levels in patients with any signs or symptoms of pancreatitis. Discontinue RYLAZE in patients with severe or hemorrhagic pancreatitis. In the case of mild pancreatitis, withhold RYLAZE until the signs and symptoms subside and amylase and/or lipase levels return to 1.5 times the ULN [see Dosage and Administration ( 2.3 )] . After resolution of mild pancreatitis, treatment with RYLAZE may be resumed. 5.3 Thrombosis Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism, have been reported in 1% of patients following treatment with RYLAZE. Discontinue RYLAZE for a thrombotic event, and administer appropriate antithrombotic therapy. Consider resumption of treatment with RYLAZE only if the patient had an uncomplicated thrombosis [see Dosage and Administration ( 2.3 )] . 5.4 Hemorrhage Bleeding was reported in 25% of patients treated with RYLAZE, and it was severe in 2%. Most commonly observed reactions were bruising (12%) and nose bleed (9%) [see Adverse Reactions ( 6.1 )] . In patients treated with L-asparaginase class products, hemorrhage may be associated with increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia. Consider appropriate replacement therapy in patients with severe or symptomatic coagulopathy [see Dosage and Administration ( 2.3 )] . 5.5 Hepatotoxicity, including Hepatic Veno-Occlusive Disease Elevated bilirubin and/or transaminases occurred in 75% of patients treated with RYLAZE in clinical trials, and 26% had Grade ≥ 3 elevations. Elevated bilirubin occurred in 28% of patients treated with RYLAZE in clinical trials, and 2% had Grade ≥ 3 elevations. Elevated transaminases occurred in 73% of patients treated with RYLAZE in clinical trials, and 25% had Grade ≥ 3 elevations [see Adverse Reactions ( 6.1 )] . Hepatotoxicity, including severe, life-threatening, and potential fatal cases of hepatic veno-occlusive disease (VOD), have been observed in patients treated with asparaginase class products in combination with standard chemotherapy, including during the induction phase of multiphase chemotherapy [see Adverse Reactions ( 6 )]. Do not administer RYLAZE to patients with severe hepatic impairment [see Contraindication ( 4 )]. Inform patients of the signs and symptoms of hepatotoxicity. Evaluate bilirubin and transaminases prior to each cycle of RYLAZE and at least weekly during cycles of treatment that include RYLAZE, through four weeks after the last dose of RYLAZE. Monitor frequently for signs and symptoms of hepatic VOD, which may include rapid weight gain, fluid retention with ascites, hepatomegaly (which may be painful), and rapid increase of bilirubin. For patients who develop abnormal liver tests after RYLAZE, more frequent monitoring for liver test abnormalities and clinical signs and symptoms of VOD is recommended. In the event of serious liver toxicity, including VOD, discontinue treatment with RYLAZE and provide supportive care [see Dosage and Administration ( 2.3 )]."],"clinical_studies_table":["
Table 5: Proportion (95% CI) with NSAA ≥ 0.1 U/mL by Simulation
RYLAZE DosageTrough Sampling Time Proportion withNSAA > 0.1 U/mL (95% CI)a
25 mg/m2 intramuscularly every 48 hours48 hours 96.0 (94.4, 97.2)
25/25/50 mg/m2 intramuscularly Monday morning/Wednesday morning/Friday afternoonFriday afternoon: 58 hours after 25 mg/m2 Wednesday morning doseb91.6 (90.4, 92.8)
Monday morning: 67 hours after 50 mg/m2 Friday afternoon dosec91.4 (90.1, 92.6)
"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility studies have not been conducted with asparaginase erwinia chrysanthemi (recombinant)-rywn. In a fertility and early embryonic development study in rats, asparaginase Erwinia chrysanthemi had no effect on male or female fertility when administered intramuscularly at doses of up to 12 mg/m 2 (approximately 0.48 times the maximum recommended human dose) every other day for a total of 35 doses. In males, decreased sperm count was observed at all doses but did not impact fertility."],"pharmacokinetics_table":["
Table 4: Simulated RYLAZE Pharmacokinetic Parameters Based on SAA
PK ParameterGeometric Mean (%CV) After Last Dose
25 mg/m2 IntramuscularlyEvery 48 Hours25/25/50 mg/m2 IntramuscularlyMonday, Wednesday, Friday
Last 25 mg/m2Wednesday morning doseLast 50 mg/m2Friday afternoon dose
Cmax (U/mL)2.3 (55%)2.3 (54%)4.1 (57%)
Ctrough (U/mL)0.46 (75%)0.3 (75%)a0.39 (87%)b
"],"adverse_reactions_table":["
Table 3: Adverse Reactions (≥ 15% Incidence) in Patients Receiving RYLAZE as a Component of Multi-Agent Chemotherapy in Study JZP458-201
Adverse ReactionRYLAZE25/25/25 mg/m2Intramuscular Dosagea(N = 33)RYLAZE25/25/50 mg/m2Intramuscular Dosagea(N = 51)
All Grades(%)Grades 3-4(%)All Grades(%)Grades 3-4(%)
Abnormal liver test*#70187527
Musculoskeletal pain*456354
Nausea*459478
Fatigue*36182218
Headache360220
Infection*b36152717
Febrile neutropenia30302727
Pyrexia306200
Hemorrhage*240276
Stomatitis2412274
Abdominal pain*210252
Decreased appetite216276
Drug hypersensitivity*216242
Hyperglycemia213124
Diarrhea*186254
Tachycardia*180162
Cough150140
Dehydration159126
Insomnia15040
Peripheral neuropathy*15060
Pancreatitis*#1202210
Hypokalemia93228
"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION • Hypersensitivity Inform patients of the risk of allergic reactions, including anaphylaxis. Instruct the patient on the symptoms of allergic reactions and to seek medical advice immediately if they experience such symptoms [see Warnings and Precautions ( 5.1 )] . • Pancreatitis Instruct patients on signs and symptoms of pancreatitis and to seek medical attention if they experience severe abdominal pain [see Warnings and Precautions ( 5.2 )] . • Thrombosis Instruct patients on the risk of thrombosis and to seek medical advice immediately if they experience headache, arm or leg swelling, shortness of breath, and chest pain [see Warnings and Precautions ( 5.3 )] . • Hemorrhage Advise patients to report any unusual bleeding or bruising to their healthcare provider [see Warnings and Precautions ( 5.4 )] . • Hepatotoxicity, including Veno-Occlusive Liver Disease Inform patients that liver problems, including severe, life-threatening, or fatal VOD and abnormalities in liver tests, may develop during RYLAZE treatment. Advise patients to report any jaundice, severe nausea or vomiting, or easy bleeding or bruising to their healthcare provider [see Warnings and Precautions ( 5.5 )] . • Pregnancy Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective non-hormonal contraception during treatment with RYLAZE and for 3 months after the last dose [see Use in Specific Populations ( 8.3 )] . • Lactation Advise women not to breastfeed during treatment with RYLAZE and for 1 week after the last dose [see Use in Specific Populations ( 8.2 )] . Manufactured by: Jazz Pharmaceuticals Ireland Limited Dublin, Ireland U.S. License No. 2167 Distributed by: Jazz Pharmaceuticals, Inc. Palo Alto, CA 94306 Protected by U.S. Patent nos. 8,288,127 and 10,787,671 RYLAZE ® is a trademark of Jazz Pharmaceuticals plc or its subsidiaries. ©2024 Jazz Pharmaceuticals"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION There are two RYLAZE regimens that can be used to replace a long-acting asparaginase product. The recommended dosages of RYLAZE are: When administered every 48 hours • 25 mg/m 2 intramuscularly every 48 hours; When administered Monday/Wednesday/Friday • 25 mg/m 2 intramuscularly on Monday morning and Wednesday morning and 50 mg/m 2 intramuscularly on Friday afternoon. ( 2.1 ) 2.1 Recommended Dosage There are two RYLAZE regimens that can be used to replace a long-acting asparaginase product. The recommended dosages of RYLAZE are: When administered every 48 hours: • 25 mg/m 2 administered intramuscularly every 48 hours; When administered on a Monday/Wednesday/Friday schedule: • 25 mg/m 2 intramuscularly on Monday morning and Wednesday morning, and 50 mg/m 2 intramuscularly on Friday afternoon. Administer the Friday afternoon dose 53 to 58 hours after the Wednesday morning dose (e.g., 8:00 am on Monday and Wednesday, and 1:00 pm to 6:00 pm on Friday) [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14 )] . Table 1 shows the number of RYLAZE dosages recommended for the intended duration of treatment for replacement of one dose of calaspargase pegol products (3 weeks of asparaginase coverage) or one dose of pegaspargase products (2 weeks of asparaginase coverage). See the full prescribing information for the long-acting asparaginase product to determine the total duration of administration of RYLAZE as replacement therapy. Table 1: Recommended Duration of RYLAZE Dosing to Replace One Long-Acting Asparaginase Dose When RYLAZE is Administered: Recommended Duration of RYLAZE to Replace Calaspargase Pegol Products Recommended Duration of RYLAZE to Replace Pegaspargase Products 25 mg/m 2 intramuscular every 48 hours Replace one dose of calaspargase pegol products with 11 doses of RYLAZE Replace one dose of pegaspargase products with 7 doses of RYLAZE 25 mg/m 2 intramuscular on Monday morning and Wednesday morning, and 50 mg/m 2 intramuscular on Friday afternoon* Replace one dose of calaspargase pegol products with 9 doses of RYLAZE Replace one dose of pegaspargase products with 6 doses of RYLAZE *See bullet above for timing of 25/25/50 mg/m 2 dosing of RYLAZE. 2.2 Recommended Premedication Premedicate patients with acetaminophen, an H-1 receptor blocker (such as diphenhydramine), and an H-2 receptor blocker (such as famotidine) 30-60 minutes prior to administration of RYLAZE to decrease the risk and severity of hypersensitivity reactions [see Warnings and Precautions ( 5.1 )] . 2.3 Recommended Monitoring and Dosage Modifications for Adverse Reactions Monitor patient’s bilirubin, transaminases, glucose, and clinical examinations prior to treatment every 2-3 weeks and as indicated clinically. If results are abnormal, monitor patients until recovery from the cycle of therapy. If an adverse reaction occurs, modify treatment according to Table 2. Table 2: Dosage Modifications Adverse Reaction Severity* Action Hypersensitivity Reaction [see Warnings and Precautions ( 5.1 )] Grade 2 • Treat the symptoms. Grade 3 to 4 • Discontinue RYLAZE permanently. Pancreatitis [see Warnings and Precautions ( 5.2 )] Grade 2 to 4 • Hold RYLAZE for elevations in lipase or amylase > 2 times the ULN**, or for symptomatic pancreatitis. • Resume treatment when lipase and amylase are < 1.5 times the ULN and symptoms are resolved. • Discontinue RYLAZE permanently if clinical necrotizing or hemorrhagic pancreatitis is confirmed. Thrombosis [see Warnings and Precautions ( 5.3 )] Uncomplicated thrombosis • Hold RYLAZE. • Treat with appropriate antithrombotic therapy. • Upon resolution of symptoms, consider resuming RYLAZE, while continuing antithrombotic therapy. Severe or life-threatening thrombosis • Discontinue RYLAZE permanently. • Treat with appropriate antithrombotic therapy. Hemorrhage [see Warnings and Precautions ( 5.4 )] Grade 3 to 4 • Hold RYLAZE. • Evaluate for coagulopathy and consider clotting factor replacement as needed. • Resume RYLAZE with the next scheduled dose if bleeding is controlled. Hepatotoxicity [see Warnings and Precautions ( 5.5 )] Total bilirubin > 3 times to ≤ 10 times the ULN • Hold RYLAZE until total bilirubin levels decrease to ≤ 1.5 times the ULN. Total bilirubin > 10 times the ULN • Discontinue RYLAZE and do not make up missed doses. * Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. ** Upper limit of normal 2.4 Preparation and Administration Instructions Ensure that medical support is available to appropriately manage anaphylactic reactions when administering RYLAZE [see Warnings and Precautions ( 5.1 )] . Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter, cloudiness, or discoloration are present, discard the vial. • Use aseptic technique. • Determine the dose, total volume of RYLAZE solution required, and the number of RYLAZE vials needed based on the individual patient’s BSA. More than one vial may be needed for a full dose. • Withdraw the indicated injection volume of RYLAZE into the syringe for injection. o Do not shake the vial. o Limit the volume of RYLAZE at a single injection site to 2 mL. o If the volume to be administered is greater than 2 mL, divide the doses equally into multiple syringes, one for each injection site. o Discard the remaining unused RYLAZE in the single-dose vial. • Administer RYLAZE by intramuscular injection. o Rotate injection sites. o Do not inject RYLAZE into scar tissue or areas that are reddened, inflamed, or swollen. • If the prepared dose is not used immediately, store the syringe(s) at room temperature 15°C to 25°C (59°F to 77°F) for up to 8 hours or refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours. The syringe does not need to be protected from light during storage."],"spl_product_data_elements":["Rylaze asparaginase erwinia chrysanthemi (recombinant)-rywn TREHALOSE DIHYDRATE SODIUM CHLORIDE SODIUM PHOSPHATE, DIBASIC, ANHYDROUS SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE ASPARAGINASE ASPARAGINASE POLYSORBATE 80"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Injection: 10 mg/0.5 mL clear to opalescent, colorless to slightly yellow solution in a single-dose vial. Injection: 10 mg/0.5 mL solution in a single-dose vial. ( 3 )"],"clinical_pharmacology_table":["
Table 4: Simulated RYLAZE Pharmacokinetic Parameters Based on SAA
PK ParameterGeometric Mean (%CV) After Last Dose
25 mg/m2 IntramuscularlyEvery 48 Hours25/25/50 mg/m2 IntramuscularlyMonday, Wednesday, Friday
Last 25 mg/m2Wednesday morning doseLast 50 mg/m2Friday afternoon dose
Cmax (U/mL)2.3 (55%)2.3 (54%)4.1 (57%)
Ctrough (U/mL)0.46 (75%)0.3 (75%)a0.39 (87%)b
"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS • Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, RYLAZE can cause fetal harm when administered to a pregnant woman. There are no available data on RYLAZE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproductive and developmental toxicity studies, intramuscular administration of asparaginase Erwinia chrysanthemi to pregnant rats and rabbits during organogenesis resulted in structural abnormalities and embryo-fetal mortality ( see Data ) at exposures below those in patients at the recommended human dose. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal Data Animal reproductive and developmental toxicity studies have not been conducted with RYLAZE. In embryofetal development studies, asparaginase Erwinia chrysanthemi was administered intramuscularly every other day during the period of organogenesis to pregnant rats (at 3, 6, or 12 mg/m 2 ) and rabbits (at 0.12, 0.30, or 0.48 mg/m 2 ). In rats given 12 mg/m 2 (approximately 0.48 times the maximum recommended human dose), maternal toxicity of decreased body weight gain was observed, as was a fetal finding of increased incidence of partially undescended thymic tissue. In rabbits, maternal toxicity consisting of decreased body weight was observed at 0.48 mg/m 2 (approximately 0.02 times the maximum recommended human dose). Increased post-implantation loss, a decrease in the number of live fetuses, and gross abnormalities (e.g., absent kidney, absent accessory lung lobe, additional subclavian artery, and delayed ossification) were observed at doses of ≥ 0.12 mg/m 2 (approximately 0.005 times the maximum recommended human dose). 8.2 Lactation Risk Summary There are no data on the presence of asparaginase erwinia chrysanthemi (recombinant)-rywn in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with RYLAZE and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential RYLAZE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Pregnancy testing is recommended in females of reproductive potential prior to initiating RYLAZE. Contraception Advise females of reproductive potential to use effective non-hormonal contraceptive methods during treatment with RYLAZE and for 3 months after the last dose. 8.4 Pediatric Use The safety and effectiveness of RYLAZE in the treatment of ALL and LBL have been established in pediatric patients 1 month to < 17 years who have developed hypersensitivity to a long-acting E. coli -derived asparaginase. Use of RYLAZE in these age groups is supported by evidence from an adequate and well-controlled study in adults and pediatric patients. The trial included 139 pediatric patients, including 2 infants (1 month to < 2 years), 99 children (2 years to < 12 years old), and 38 adolescents (12 years to < 17 years old). There were no clinically meaningful differences in safety or nadir serum asparaginase activity across age groups. The safety and effectiveness of RYLAZE have not been established in pediatric patients younger than 1 month of age. 8.5 Geriatric Use Clinical studies of RYLAZE did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients."],"dosage_and_administration_table":["
Table 1: Recommended Duration of RYLAZE Dosing to Replace One Long-Acting Asparaginase Dose
When RYLAZE is Administered:Recommended Duration of RYLAZE to Replace Calaspargase Pegol ProductsRecommended Duration of RYLAZE to Replace Pegaspargase Products
25 mg/m2 intramuscular every 48 hoursReplace one dose of calaspargase pegol products with 11 doses of RYLAZEReplace one dose of pegaspargase products with 7 doses of RYLAZE
25 mg/m2 intramuscular on Monday morning and Wednesday morning, and 50 mg/m2 intramuscular on Friday afternoon*Replace one dose of calaspargase pegol products with 9 doses of RYLAZEReplace one dose of pegaspargase products with 6 doses of RYLAZE
","Treat the symptoms.Discontinue RYLAZE permanently.Hold RYLAZE for elevations in lipase or amylase > 2 times the ULN**, or for symptomatic pancreatitis.Resume treatment when lipase and amylase are < 1.5 times the ULN and symptoms are resolved.Discontinue RYLAZE permanently if clinical necrotizing or hemorrhagic pancreatitis is confirmed.Hold RYLAZE.Treat with appropriate antithrombotic therapy.Upon resolution of symptoms, consider resuming RYLAZE, while continuing antithrombotic therapy.Discontinue RYLAZE permanently.Treat with appropriate antithrombotic therapy.Hold RYLAZE.Evaluate for coagulopathy and consider clotting factor replacement as needed.Resume RYLAZE with the next scheduled dose if bleeding is controlled.Hold RYLAZE until total bilirubin levels decrease to ≤ 1.5 times the ULN.Discontinue RYLAZE and do not make up missed doses.
Table 2: Dosage Modifications
Adverse ReactionSeverity*Action
Hypersensitivity Reaction [see Warnings and Precautions (5.1)]Grade 2
•
Grade 3 to 4
•
Pancreatitis [see Warnings and Precautions (5.2)]Grade 2 to 4
•••
Thrombosis [see Warnings and Precautions (5.3)]Uncomplicated thrombosis
•••
Severe or life-threatening thrombosis
••
Hemorrhage [see Warnings and Precautions (5.4)]Grade 3 to 4
•••
Hepatotoxicity [see Warnings and Precautions (5.5)]Total bilirubin > 3 times to ≤ 10 times the ULN
•
Total bilirubin > 10 times the ULN
•
"],"package_label_principal_display_panel":["PACKAGE/LABEL PRINCIPAL DISPLAY PANEL carton-label","Package/Label Display Panel 3 vials (NDC 68727-900-01) 1 carton (NDC 68727-900-03) asparaginase erwinia chrysanthemi (recombinant)-rywn RYLAZE™ Injection, for intramuscular use 10 mg/0.5 mL vial"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility studies have not been conducted with asparaginase erwinia chrysanthemi (recombinant)-rywn. In a fertility and early embryonic development study in rats, asparaginase Erwinia chrysanthemi had no effect on male or female fertility when administered intramuscularly at doses of up to 12 mg/m 2 (approximately 0.48 times the maximum recommended human dose) every other day for a total of 35 doses. In males, decreased sperm count was observed at all doses but did not impact fertility."]},"tags":[{"label":"Asparagine-specific Enzyme","category":"class"},{"label":"Small Molecule","category":"modality"},{"label":"L01XX02","category":"atc"},{"label":"Intramuscular","category":"route"},{"label":"Injection","category":"form"},{"label":"Active","category":"status"},{"label":"Acute lymphoid leukemia","category":"indication"},{"label":"Merck","category":"company"},{"label":"Approved 1990s","category":"decade"},{"label":"Antineoplastic Agents","category":"pharmacology"}],"phase":"marketed","safety":{"boxedWarnings":[],"safetySignals":[{"llr":696.337,"date":"","count":464,"signal":"Febrile neutropenia","source":"DrugCentral FAERS","actionTaken":"Reported 464 times (LLR=696)"},{"llr":575.971,"date":"","count":134,"signal":"Secondary immunodeficiency","source":"DrugCentral FAERS","actionTaken":"Reported 134 times (LLR=576)"},{"llr":528.001,"date":"","count":120,"signal":"Mycobacterium chelonae infection","source":"DrugCentral FAERS","actionTaken":"Reported 120 times (LLR=528)"},{"llr":435.616,"date":"","count":165,"signal":"Posterior reversible encephalopathy syndrome","source":"DrugCentral FAERS","actionTaken":"Reported 165 times (LLR=436)"},{"llr":429.37,"date":"","count":181,"signal":"Bacterial infection","source":"DrugCentral FAERS","actionTaken":"Reported 181 times (LLR=429)"},{"llr":393.723,"date":"","count":131,"signal":"Venoocclusive liver disease","source":"DrugCentral FAERS","actionTaken":"Reported 131 times (LLR=394)"},{"llr":352.148,"date":"","count":73,"signal":"Human bocavirus infection","source":"DrugCentral FAERS","actionTaken":"Reported 73 times (LLR=352)"},{"llr":351.867,"date":"","count":100,"signal":"Human herpesvirus 6 infection","source":"DrugCentral FAERS","actionTaken":"Reported 100 times (LLR=352)"},{"llr":331.747,"date":"","count":148,"signal":"Clostridium difficile colitis","source":"DrugCentral FAERS","actionTaken":"Reported 148 times (LLR=332)"},{"llr":329.737,"date":"","count":95,"signal":"Parainfluenzae virus infection","source":"DrugCentral FAERS","actionTaken":"Reported 95 times (LLR=330)"},{"llr":308.166,"date":"","count":119,"signal":"Haematotoxicity","source":"DrugCentral FAERS","actionTaken":"Reported 119 times (LLR=308)"},{"llr":304.698,"date":"","count":92,"signal":"Pseudomonal sepsis","source":"DrugCentral FAERS","actionTaken":"Reported 92 times (LLR=305)"},{"llr":302.311,"date":"","count":140,"signal":"Osteonecrosis","source":"DrugCentral FAERS","actionTaken":"Reported 140 times (LLR=302)"},{"llr":284.582,"date":"","count":119,"signal":"Bronchopulmonary aspergillosis","source":"DrugCentral FAERS","actionTaken":"Reported 119 times (LLR=285)"},{"llr":280.48,"date":"","count":85,"signal":"Pneumatosis intestinalis","source":"DrugCentral FAERS","actionTaken":"Reported 85 times (LLR=280)"}],"commonSideEffects":[{"effect":"abnormal liver test","drugRate":"70","_validated":true,"placeboRate":""},{"effect":"abnormal liver test","drugRate":"75","_validated":true,"placeboRate":""},{"effect":"musculoskeletal pain","drugRate":"45","_validated":true,"placeboRate":""},{"effect":"musculoskeletal pain","drugRate":"35","_validated":true,"placeboRate":""},{"effect":"nausea","drugRate":"45","_validated":true,"placeboRate":""},{"effect":"nausea","drugRate":"47","_validated":true,"placeboRate":""},{"effect":"fatigue","drugRate":"36","_validated":true,"placeboRate":""},{"effect":"fatigue","drugRate":"22","_validated":true,"placeboRate":""},{"effect":"headache","drugRate":"36","_validated":true,"placeboRate":""},{"effect":"headache","drugRate":"22","_validated":true,"placeboRate":""},{"effect":"infection","drugRate":"36","_validated":true,"placeboRate":""},{"effect":"infection","drugRate":"27","_validated":true,"placeboRate":""},{"effect":"febrile neutropenia","drugRate":"30","_validated":true,"placeboRate":""},{"effect":"febrile neutropenia","drugRate":"27","_validated":true,"placeboRate":""},{"effect":"pyrexia","drugRate":"30","_validated":true,"placeboRate":""},{"effect":"pyrexia","drugRate":"20","_validated":true,"placeboRate":""},{"effect":"hemorrhage","drugRate":"24","_validated":true,"placeboRate":""},{"effect":"hemorrhage","drugRate":"27","_validated":true,"placeboRate":""},{"effect":"stomatitis","drugRate":"24","_validated":true,"placeboRate":""},{"effect":"stomatitis","drugRate":"27","_validated":true,"placeboRate":""},{"effect":"abdominal pain","drugRate":"21","_validated":true,"placeboRate":""},{"effect":"abdominal pain","drugRate":"25","_validated":true,"placeboRate":""},{"effect":"decreased appetite","drugRate":"21","_validated":true,"placeboRate":""},{"effect":"decreased appetite","drugRate":"27","_validated":true,"placeboRate":""},{"effect":"drug hypersensitivity","drugRate":"21","_validated":true,"placeboRate":""},{"effect":"drug hypersensitivity","drugRate":"24","_validated":true,"placeboRate":""},{"effect":"hyperglycemia","drugRate":"21","_validated":true,"placeboRate":""},{"effect":"hyperglycemia","drugRate":"12","_validated":true,"placeboRate":""},{"effect":"diarrhea","drugRate":"18","_validated":true,"placeboRate":""},{"effect":"diarrhea","drugRate":"25","_validated":true,"placeboRate":""},{"effect":"tachycardia","drugRate":"18","_validated":true,"placeboRate":""},{"effect":"tachycardia","drugRate":"16","_validated":true,"placeboRate":""},{"effect":"cough","drugRate":"15","_validated":true,"placeboRate":""},{"effect":"cough","drugRate":"14","_validated":true,"placeboRate":""},{"effect":"dehydration","drugRate":"15","_validated":true,"placeboRate":""},{"effect":"dehydration","drugRate":"12","_validated":true,"placeboRate":""},{"effect":"insomnia","drugRate":"15","_validated":true,"placeboRate":""},{"effect":"insomnia","drugRate":"4","_validated":true,"placeboRate":""},{"effect":"peripheral neuropathy","drugRate":"15","_validated":true,"placeboRate":""},{"effect":"peripheral neuropathy","drugRate":"6","_validated":true,"placeboRate":""},{"effect":"pancreatitis","drugRate":"12","_validated":true,"placeboRate":""},{"effect":"pancreatitis","drugRate":"22","_validated":true,"placeboRate":""},{"effect":"hypokalemia","drugRate":"9","_validated":true,"placeboRate":""},{"effect":"hypokalemia","drugRate":"22","_validated":true,"placeboRate":""}],"contraindications":["History of serious hypersensitivity reactions to Erwinia asparaginase, including anaphylaxis.","History of serious pancreatitis during previous asparaginase therapy.","History of serious thrombosis during previous asparaginase therapy.","History of serious hemorrhagic events during previous asparaginase therapy.","Severe hepatic impairment.","History of serious hypersensitivity reactions to RYLAZE, including anaphylaxis.","History of serious pancreatitis during previous L-asparaginase therapy.","History of serious thrombosis during previous L-asparaginase therapy.","History of serious hemorrhagic events during previous L-asparaginase therapy."],"specialPopulations":{"Lactation":"There are no data on the presence of asparaginase erwinia chrysanthemi (recombinant)-rywn in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with RYLAZE and for week after the last dose.","Pregnancy":"Based on findings from animal reproduction studies, RYLAZE can cause fetal harm when administered to pregnant woman. There are no available data on RYLAZE use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproductive and developmental toxicity studies, intramuscular administration of asparaginase Erwinia chrysanthemi to pregnant rats and rabbits during organogenesis resulted in structural abnormalities and embryo-fetal mortality (see Data) at exposures below those in patients at the recommended human dose. Advise pregnant women of the potential risk to fetus.In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are to 4% and 15 to 20%, respectively.DataAnimal DataAnimal reproductive and developmental toxicity studies have not been conducted with RYLAZE.In embryofetal development studies, asparaginase Erwinia chrysanthemi was administered intramuscularly every other day during the period of organogenesis to pregnant rats (at 3, 6, or 12 mg/m2) and rabbits (at 0.12, 0.30, or 0.48 mg/m2). In rats given 12 mg/m2 (approximately 0.48 times the maximum recommended human dose), maternal toxicity of decreased body weight gain was observed, as was fetal finding of ","Geriatric use":"Clinical studies of RYLAZE did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients.","Paediatric use":"The safety and effectiveness of RYLAZE in the treatment of ALL and LBL have been established in pediatric patients month to 17 years who have developed hypersensitivity to long-acting E. coli-derived asparaginase. Use of RYLAZE in these age groups is supported by evidence from an adequate and well-controlled study in adults and pediatric patients. The trial included 84 pediatric patients, including infants (1 month to 2 years), 62 children (2 years to 12 years old), and 20 adolescents (13 to 17 years) with ALL or LBL."},"discontinuationRates":[{"trial":"JZP458-201","drugArm":"10%","placeboArm":"","commonReason":"pancreatitis (5%), drug hypersensitivity (4%), and infection (1%)"}],"seriousAdverseEvents":[{"event":"febrile neutropenia","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"infection","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"drug hypersensitivity","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"pyrexia","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"nausea","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"dehydration","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"stomatitis","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"acute kidney injury","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"pancreatitis","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"diarrhea","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"},{"event":"viral infection","detail":"most frequent nonhematological serious adverse reaction","severity":"serious","incidence":"≥ 5%"}]},"trials":[],"aliases":[],"company":"Merck & Co.","patents":[],"pricing":[],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=ASPARAGINASE","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-20T03:33:33.080057+00:00"},"aiSummary":{"url":"","method":"ai_extraction","source":"AI Strategic Summary","aiModel":"featherless","rawText":"","confidence":0.9,"sourceType":"ai_extraction","retrievedAt":"2026-04-20T03:35:49.681594+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-20T03:33:39.200084+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=ASPARAGINASE","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-20T03:33:39.489172+00:00"},"mechanism.drugClass":{"url":"https://api.fda.gov/drug/label.json","method":"deterministic","source":"FDA Label (EPC)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:33:29.885121+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:33:29.885145+00:00"},"indications.approved":{"url":"","method":"ai_extraction","source":"FDA Label + AI","aiModel":"featherless","rawText":"","confidence":0.9,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:35:42.497009+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:33:29.885150+00:00"},"mechanism.oneSentence":{"url":"","method":"ai_extraction","source":"FDA Label + AI","aiModel":"featherless","rawText":"12.1 Mechanism of Action Asparaginase erwinia chrysanthemi (recombinant)-rywn is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The pharmacological effect of RYLAZE is based on the killing of leukemic cells due to depletion of plasma asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival.","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:33:54.198658+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Asparagine hydrolytic enzyme","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T03:33:40.538364+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2108989/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T03:33:40.191382+00:00"},"safety.commonSideEffects":{"url":"","method":"ai_extraction","source":"FDA Label + AI","aiModel":"featherless","rawText":"6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in greater detail in other sections of the labeling: • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] • Pancreatic Toxicity [see Warnings and Precautions ( 5.2 )] • Thrombosis [see Warnings and Precautions ( 5.3 )] • Hemorrhage [see Warnings and Precautions ( 5.4 )] • Hepatotoxicity, including VOD [see Warnings and Precautions ( 5.5 )] Most common adverse reactions (incidence > 20%) are ab","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:35:15.991675+00:00"},"safety.contraindications":{"url":"","method":"ai_extraction","source":"FDA Label + AI","aiModel":"featherless","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:35:24.785437+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"BLA761179","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:33:29.885153+00:00"}},"allNames":"elspar","offLabel":[],"synonyms":["asparaginase","elspar"],"timeline":[{"date":"1994-02-01","type":"positive","source":"DrugCentral","milestone":"FDA approval (Merck)"}],"aiSummary":"ASPARAGINASE (Elspar), marketed by Merck & Co., is a key treatment for Acute Lymphoblastic Leukemia (ALL) that depletes plasma asparagine to kill leukemic cells. The drug's key strength lies in its unique mechanism of action, which differentiates it from other same-class competitors such as altretamine, hydroxycarbamide, pentostatin, masoprocol, and mitotane. A primary risk is the key composition patent expiry in 2028, which could lead to increased competition from generics.","brandName":"Elspar","ecosystem":[{"indication":"Acute lymphoid leukemia","otherDrugs":[{"name":"betamethasone","slug":"betamethasone","company":""},{"name":"betamethasone acetate","slug":"betamethasone-acetate","company":""},{"name":"clofarabine","slug":"clofarabine","company":"Genzyme"},{"name":"cortisone acetate","slug":"cortisone-acetate","company":""}],"globalPrevalence":453000}],"mechanism":{"target":"L-asparagine","novelty":"Follow-on","modality":"Enzyme","drugClass":"Asparagine-specific Enzyme [EPC]","explanation":"RYLAZE works by converting L-asparagine into aspartic acid and ammonia. This depletion of asparagine in the blood starves leukemic cells, which rely on external sources of asparagine because they can't produce enough themselves.","oneSentence":"RYLAZE kills leukemic cells by depleting plasma asparagine, which they need for survival.","technicalDetail":"Asparaginase erwinia chrysanthemi (recombinant)-rywn is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival."},"commercial":{"launchDate":"1994","revenueYear":2024,"_launchSource":"DrugCentral (FDA 1994-02-01, MERCK)","annualRevenue":600,"revenueSource":"Jazz 10-K FY2024","revenueCurrency":"USD"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/5070","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=ASPARAGINASE","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=ASPARAGINASE","fields":["publications"],"source":"PubMed/NCBI"}],"_enrichedAt":"2026-03-30T08:50:25.946691","_validation":{"fieldsValidated":4,"lastValidatedAt":"2026-04-20T03:35:49.682064+00:00","fieldsConflicting":0,"overallConfidence":0.95},"biosimilars":[{"form":"INJECTION","route":"INTRAMUSCULAR","company":"Jazz Pharmaceuticals, Inc.","brandName":"Rylaze","isOriginal":false,"marketingStatus":"BLA"}],"competitors":[{"drugName":"altretamine","drugSlug":"altretamine","fdaApproval":"1990-12-26","patentStatus":"Unknown","relationship":"same-class"},{"drugName":"hydroxycarbamide","drugSlug":"hydroxycarbamide","fdaApproval":"1967-12-07","relationship":"same-class"},{"drugName":"pentostatin","drugSlug":"pentostatin","fdaApproval":"1991-10-11","genericCount":2,"patentStatus":"Off-patent — generic available","relationship":"same-class"},{"drugName":"masoprocol","drugSlug":"masoprocol","fdaApproval":"1992-09-04","patentStatus":"Unknown","relationship":"same-class"},{"drugName":"mitotane","drugSlug":"mitotane","fdaApproval":"1970-07-08","patentStatus":"Unknown","relationship":"same-class"},{"drugName":"pegaspargase","drugSlug":"pegaspargase","fdaApproval":"1994-02-01","relationship":"same-class"},{"drugName":"arsenic trioxide","drugSlug":"arsenic-trioxide","fdaApproval":"2000-09-25","genericCount":11,"patentStatus":"Off-patent — generic available","relationship":"same-class"},{"drugName":"denileukin diftitox","drugSlug":"denileukin-diftitox","fdaApproval":"1999-02-05","relationship":"same-class"},{"drugName":"celecoxib","drugSlug":"celecoxib","fdaApproval":"1998-12-31","patentExpiry":"May 27, 2036","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"anagrelide","drugSlug":"anagrelide","fdaApproval":"1997-03-14","genericCount":9,"patentStatus":"Off-patent — generic available","relationship":"same-class"},{"drugName":"omacetaxine mepesuccinate","drugSlug":"omacetaxine-mepesuccinate","fdaApproval":"2012-10-26","patentExpiry":"Oct 26, 2026","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"eribulin","drugSlug":"eribulin","fdaApproval":"2010-11-15","patentExpiry":"Jul 8, 2027","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"aflibercept","drugSlug":"aflibercept","fdaApproval":"2011-11-18","relationship":"same-class"},{"drugName":"venetoclax","drugSlug":"venetoclax","fdaApproval":"2016-04-11","patentExpiry":"Sep 6, 2033","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"enasidenib","drugSlug":"enasidenib","fdaApproval":"2017-08-01","patentExpiry":"Sep 16, 2034","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"ivosidenib","drugSlug":"ivosidenib","fdaApproval":"2018-07-20","patentExpiry":"Oct 18, 2036","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"selinexor","drugSlug":"selinexor","fdaApproval":"2019-07-03","patentExpiry":"Jul 3, 2033","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"tagraxofusp","drugSlug":"tagraxofusp","fdaApproval":"2018-12-21","relationship":"same-class"},{"drugName":"lurbinectedin","drugSlug":"lurbinectedin","fdaApproval":"2020-06-15","patentExpiry":"May 29, 2040","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"tazemetostat","drugSlug":"tazemetostat","fdaApproval":"2020-01-23","patentExpiry":"Sep 12, 2031","patentStatus":"Patent protected","relationship":"same-class"}],"genericName":"asparaginase","indications":{"approved":[{"id":"asparaginase-acute-lymphoblastic-leukemia-(","name":"Acute Lymphoblastic Leukemia (ALL)","dosing":null,"approvals":[],"diseaseId":"","eligibility":"Adult and pediatric patients 1 month or older with hypersensitivity to E. coli-derived asparaginase","pivotalTrial":null,"restrictions":[],"patientPopulation":"Adult and pediatric patients 1 month or older with hypersensitivity to E. coli-derived asparaginase","diagnosticRequired":null,"brandNameForIndication":"Elspar"},{"id":"asparaginase-lymphoblastic-lymphoma-(lbl)","name":"Lymphoblastic Lymphoma (LBL)","dosing":null,"approvals":[],"diseaseId":"","eligibility":"Adult and pediatric patients 1 month or older with hypersensitivity to E. coli-derived asparaginase","pivotalTrial":null,"restrictions":[],"patientPopulation":"Adult and pediatric patients 1 month or older with hypersensitivity to E. coli-derived asparaginase","diagnosticRequired":null,"brandNameForIndication":"Elspar"}],"offLabel":[],"pipeline":[]},"drugCategory":"active","labelChanges":[],"relatedDrugs":[{"drugId":"altretamine","brandName":"altretamine","genericName":"altretamine","approvalYear":"1990","relationship":"same-class"},{"drugId":"hydroxycarbamide","brandName":"hydroxycarbamide","genericName":"hydroxycarbamide","approvalYear":"1967","relationship":"same-class"},{"drugId":"pentostatin","brandName":"pentostatin","genericName":"pentostatin","approvalYear":"1991","relationship":"same-class"},{"drugId":"masoprocol","brandName":"masoprocol","genericName":"masoprocol","approvalYear":"1992","relationship":"same-class"},{"drugId":"mitotane","brandName":"mitotane","genericName":"mitotane","approvalYear":"1970","relationship":"same-class"},{"drugId":"pegaspargase","brandName":"pegaspargase","genericName":"pegaspargase","approvalYear":"1994","relationship":"same-class"},{"drugId":"arsenic-trioxide","brandName":"arsenic trioxide","genericName":"arsenic trioxide","approvalYear":"2000","relationship":"same-class"},{"drugId":"denileukin-diftitox","brandName":"denileukin diftitox","genericName":"denileukin diftitox","approvalYear":"1999","relationship":"same-class"},{"drugId":"celecoxib","brandName":"celecoxib","genericName":"celecoxib","approvalYear":"1998","relationship":"same-class"},{"drugId":"anagrelide","brandName":"anagrelide","genericName":"anagrelide","approvalYear":"1997","relationship":"same-class"}],"trialDetails":[{"nctId":"NCT04145531","phase":"PHASE2,PHASE3","title":"An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL)","status":"COMPLETED","sponsor":"Jazz Pharmaceuticals","isPivotal":true,"startDate":"2019-12-27","conditions":["Acute Lymphoblastic Leukemia","Lymphoblastic Leukemia"],"enrollment":229,"completionDate":"2022-07-13"},{"nctId":"NCT06317662","phase":"PHASE2","title":"Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia","status":"RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2025-06-05","conditions":["Acute Leukemia of Ambiguous Lineage","B Acute Lymphoblastic Leukemia"],"enrollment":153,"completionDate":"2028-12-31"},{"nctId":"NCT03914625","phase":"PHASE3","title":"A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2019-07-03","conditions":["B Acute Lymphoblastic Leukemia","B Lymphoblastic Lymphoma","Down Syndrome"],"enrollment":6720,"completionDate":"2027-09-30"},{"nctId":"NCT05748171","phase":"PHASE2","title":"A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL","status":"RECRUITING","sponsor":"Pfizer","startDate":"2023-05-17","conditions":["ACUTE LYMPHOBLASTIC LEUKEMIA"],"enrollment":100,"completionDate":"2036-11-04"},{"nctId":"NCT05681260","phase":"PHASE3","title":"Capizzi Escalating Methotrexate Versus High Dose Methotrexate in Children With Newly Diagnosed T-cell Lymphoblastic Lymphoma (T-LBL)","status":"RECRUITING","sponsor":"Children's Cancer Group, China","startDate":"2023-02-06","conditions":["T-cell Lymphoblastic Lymphoma"],"enrollment":200,"completionDate":"2029-12-31"},{"nctId":"NCT02845882","phase":"PHASE3","title":"LBL-2016 for Children or Adolescents in China","status":"ACTIVE_NOT_RECRUITING","sponsor":"Children's Cancer Group, China","startDate":"2016-01","conditions":["Lymphoblastic Lymphoma"],"enrollment":150,"completionDate":"2031-12"},{"nctId":"NCT06918431","phase":"PHASE2","title":"Asparaginase Erwinia Chrysanthemi With Chemotherapy for the Treatment of High-Risk Adults With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma","status":"RECRUITING","sponsor":"City of Hope Medical Center","startDate":"2025-10-10","conditions":["B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative","Lymphoblastic Lymphoma"],"enrollment":53,"completionDate":"2029-03-30"},{"nctId":"NCT06124157","phase":"PHASE3","title":"A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)","status":"RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2025-05-30","conditions":["B Acute Lymphoblastic Leukemia"],"enrollment":222,"completionDate":"2030-12-01"},{"nctId":"NCT06738368","phase":"PHASE2","title":"Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) With or Without Rituximab Plus Recombinant Erwinia Asparaginase (JZP458) for the Treatment of Newly Diagnosed Ph Negative B-Acute Lymphoblastic Leukemia or T Acute Lymphoblastic Leukemia","status":"RECRUITING","sponsor":"University of Washington","startDate":"2026-04-01","conditions":["B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative","T Acute Lymphoblastic Leukemia"],"enrollment":30,"completionDate":"2028-07-30"},{"nctId":"NCT07133997","phase":"PHASE1","title":"Recombinant Erwinia Asparaginase and Venetoclax in Combination With Blinatumomab for the Treatment of Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukemia","status":"NOT_YET_RECRUITING","sponsor":"City of Hope Medical Center","startDate":"2026-06-01","conditions":["Recurrent B Acute Lymphoblastic Leukemia","Refractory B Acute Lymphoblastic Leukemia"],"enrollment":26,"completionDate":"2027-05-08"},{"nctId":"NCT05602194","phase":"PHASE3","title":"Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma","status":"RECRUITING","sponsor":"Children's Oncology Group","startDate":"2023-08-14","conditions":["B Acute Lymphoblastic Leukemia","B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1","B Acute Lymphoblastic Leukemia, BCR-ABL1-Like","Lymphoblastic Lymphoma","Mixed Phenotype Acute Leukemia","T Acute Lymphoblastic Leukemia"],"enrollment":440,"completionDate":"2028-12-30"},{"nctId":"NCT05292664","phase":"PHASE1","title":"Venetoclax Basket Trial for High Risk Hematologic Malignancies","status":"RECRUITING","sponsor":"Andrew E. Place, MD","startDate":"2023-03-29","conditions":["Myelodysplastic Syndromes, de Novo","Myelodysplastic Syndromes, Secondary","Myelodysplastic Syndromes, Previously Treated","Treatment-Related Acute Myeloid Leukemia","Therapy-Related Myelodysplastic Syndrome","Acute Lymphoblastic Leukemia, in Relapse","Acute Lymphoblastic Leukemia With Failed Remission","Lymphoblastic Lymphoma, in Relapse","Lymphoblastic Lymphoma, Refractory","Acute Leukemia of Ambiguous Lineage in Relapse","Acute Leukemia of Ambiguous Lineage"],"enrollment":30,"completionDate":"2030-07-02"},{"nctId":"NCT02723994","phase":"PHASE2","title":"A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia","status":"COMPLETED","sponsor":"Incyte Corporation","startDate":"2016-09-30","conditions":["Leukemia"],"enrollment":171,"completionDate":"2026-03-03"},{"nctId":"NCT03959085","phase":"PHASE3","title":"Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy","status":"RECRUITING","sponsor":"Children's Oncology Group","startDate":"2019-10-31","conditions":["B Acute Lymphoblastic Leukemia","B Lymphoblastic Lymphoma","Central Nervous System Leukemia","Mixed Phenotype Acute Leukemia","Testicular Leukemia"],"enrollment":5951,"completionDate":"2032-03-31"},{"nctId":"NCT05157971","phase":"PHASE1","title":"Venetoclax and a Pediatric-Inspired Regimen for the Treatment of Newly Diagnosed B Cell Acute Lymphoblastic Leukemia","status":"RECRUITING","sponsor":"City of Hope Medical Center","startDate":"2022-03-17","conditions":["B Acute Lymphoblastic Leukemia","Ph-Like Acute Lymphoblastic Leukemia"],"enrollment":24,"completionDate":"2026-05-12"},{"nctId":"NCT03150693","phase":"PHASE3","title":"Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia","status":"SUSPENDED","sponsor":"Alliance for Clinical Trials in Oncology","startDate":"2017-09-20","conditions":["B Acute Lymphoblastic Leukemia"],"enrollment":310,"completionDate":"2027-08"},{"nctId":"NCT04293562","phase":"PHASE3","title":"A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations","status":"RECRUITING","sponsor":"Children's Oncology Group","startDate":"2020-07-21","conditions":["Acute Myeloid Leukemia"],"enrollment":1186,"completionDate":"2029-06-30"},{"nctId":"NCT03007147","phase":"PHASE3","title":"Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"Children's Oncology Group","startDate":"2017-08-08","conditions":["Acute Lymphoblastic Leukemia","B Acute Lymphoblastic Leukemia","Mixed Phenotype Acute Leukemia","T Acute Lymphoblastic Leukemia"],"enrollment":475,"completionDate":"2027-09-30"},{"nctId":"NCT02981628","phase":"PHASE2","title":"Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia","status":"RECRUITING","sponsor":"Children's Oncology Group","startDate":"2017-06-19","conditions":["Recurrent B Acute Lymphoblastic Leukemia","Recurrent B Lymphoblastic Lymphoma","Refractory B Acute Lymphoblastic Leukemia","Refractory B Lymphoblastic Lymphoma"],"enrollment":80,"completionDate":"2026-12-31"},{"nctId":"NCT07008027","phase":"","title":"Real World Asparaginase Therapy Toxicity","status":"NOT_YET_RECRUITING","sponsor":"St. Jude Children's Research Hospital","startDate":"2026-03","conditions":["Drug Toxicity"],"enrollment":200,"completionDate":"2031-07"},{"nctId":"NCT07418879","phase":"NA","title":"A Real-world Study of Pralsetinib Combined With Leucogen in the Treatment of RET Fusion-positive NSCLC","status":"NOT_YET_RECRUITING","sponsor":"Fudan University","startDate":"2026-02-05","conditions":["Non-small Cell Lung Cancer","RET Fusion","Pralsetinib"],"enrollment":25,"completionDate":"2028-12-31"},{"nctId":"NCT00400946","phase":"PHASE3","title":"05-001: Treatment of Acute Lymphoblastic Leukemia in Children","status":"COMPLETED","sponsor":"Dana-Farber Cancer Institute","startDate":"2005-04","conditions":["Drug/Agent Toxicity by Tissue/Organ","Leukemia"],"enrollment":800,"completionDate":"2019-06"},{"nctId":"NCT07409168","phase":"","title":"Multi-modal Fusion Model and Deep Learning for Predicting Treatment Response in NKTCL","status":"NOT_YET_RECRUITING","sponsor":"Sun Yat-sen University","startDate":"2026-02-15","conditions":["Natural Killer/T-cell Lymphoma"],"enrollment":100,"completionDate":"2027-12-31"},{"nctId":"NCT06600659","phase":"","title":"A Study to Determine Number of Patients Who Develop High Ammonia Levels After Receiving Recombinant Erwinia Asparaginase","status":"RECRUITING","sponsor":"Mayo Clinic","startDate":"2023-11-02","conditions":["Hematopoietic and Lymphatic System Neoplasm","Acute Lymphobkastic Leukemia"],"enrollment":10,"completionDate":"2026-12-01"},{"nctId":"NCT01574274","phase":"PHASE2","title":"SC-PEG Asparaginase vs. Oncaspar in Pediatric Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"Dana-Farber Cancer Institute","startDate":"2012-06","conditions":["Acute Lymphoblastic Leukemia","Lymphoblastic Lymphoma"],"enrollment":240,"completionDate":"2027-07-01"},{"nctId":"NCT07380646","phase":"PHASE2","title":"the Efficacy of Leucogen in Preventing the Risk of Ribociclib-Associated Neutropenia in Early Breast Cancer","status":"NOT_YET_RECRUITING","sponsor":"Second Affiliated Hospital, School of Medicine, Zhejiang University","startDate":"2026-01-01","conditions":["Leucogen","Ribociclib","Neutropenia (Low White Blood Cell Count)","Breast Cancer"],"enrollment":94,"completionDate":"2028-06-01"},{"nctId":"NCT03164057","phase":"PHASE2","title":"A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"St. Jude Children's Research Hospital","startDate":"2017-06-15","conditions":["Acute Myeloid Leukemia","Myelodysplastic Syndromes"],"enrollment":206,"completionDate":"2027-06"},{"nctId":"NCT00590915","phase":"","title":"Erwinase Master Treatment Protocol","status":"NO_LONGER_AVAILABLE","sponsor":"Phoenix Children's Hospital","startDate":"","conditions":["Leukemia, Acute Lymphoblastic","Acute Lymphoid Leukemia"],"enrollment":0,"completionDate":""},{"nctId":"NCT03020030","phase":"PHASE3","title":"Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents","status":"ACTIVE_NOT_RECRUITING","sponsor":"Dana-Farber Cancer Institute","startDate":"2017-03-03","conditions":["Acute Lymphoblastic Leukemia, Pediatric"],"enrollment":560,"completionDate":"2034-11"},{"nctId":"NCT05848687","phase":"PHASE1,PHASE2","title":"TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II","status":"RECRUITING","sponsor":"Tanja Andrea Gruber","startDate":"2023-11-03","conditions":["Lymphoblastic Leukemia"],"enrollment":90,"completionDate":"2033-12"},{"nctId":"NCT03808610","phase":"PHASE1,PHASE2","title":"Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"M.D. Anderson Cancer Center","startDate":"2019-04-03","conditions":["Recurrent B Acute Lymphoblastic Leukemia","Recurrent T Acute Lymphoblastic Leukemia","Refractory B Acute Lymphoblastic Leukemia","Refractory T Acute Lymphoblastic Leukemia"],"enrollment":50,"completionDate":"2026-12-31"},{"nctId":"NCT00501826","phase":"PHASE2","title":"Combination Chemotherapy and Nelarabine in Treating Patients With T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma","status":"RECRUITING","sponsor":"M.D. Anderson Cancer Center","startDate":"2007-07-11","conditions":["T Acute Lymphoblastic Leukemia","T Lymphoblastic Lymphoma"],"enrollment":160,"completionDate":"2026-10-31"},{"nctId":"NCT07072585","phase":"PHASE2,PHASE3","title":"Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL)","status":"NOT_YET_RECRUITING","sponsor":"Children's Oncology Group","startDate":"2026-06-28","conditions":["Stage II T Lymphoblastic Leukemia/Lymphoma","Stage III T Lymphoblastic Leukemia/Lymphoma","Stage IV T Lymphoblastic Leukemia/Lymphoma","T Acute Lymphoblastic Leukemia","T Lymphoblastic Lymphoma"],"enrollment":1708,"completionDate":"2035-09-01"},{"nctId":"NCT04195347","phase":"PHASE1,PHASE2","title":"Study of CM4620 to Reduce the Severity of Pancreatitis Due to Asparaginase","status":"RECRUITING","sponsor":"St. Jude Children's Research Hospital","startDate":"2020-09-04","conditions":["Acute Pancreatitis"],"enrollment":42,"completionDate":"2029-01"},{"nctId":"NCT05761171","phase":"PHASE2","title":"A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"Children's Oncology Group","startDate":"2024-01-08","conditions":["Recurrent Acute Leukemia of Ambiguous Lineage","Recurrent Acute Lymphoblastic Leukemia","Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage","Recurrent Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged","Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia","Recurrent Mixed Phenotype Acute Leukemia","Refractory Acute Leukemia of Ambiguous Lineage","Refractory Acute Lymphoblastic Leukemia","Refractory Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage","Refractory Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged","Refractory Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia","Refractory Mixed Phenotype Acute Leukemia"],"enrollment":78,"completionDate":"2027-12-31"},{"nctId":"NCT02881086","phase":"PHASE3","title":"Optimization of Therapy in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma by Individualised, Targeted and Intensified Treatment","status":"COMPLETED","sponsor":"Goethe University","startDate":"2016-08","conditions":["Acute Lymphoblastic Leukemia","Lymphoblastic Lymphoma"],"enrollment":1023,"completionDate":"2024-12"},{"nctId":"NCT07205536","phase":"PHASE2","title":"Clinical Study of Thiopegfilgrastim for Preventing Bone Marrow Suppression in Thoracic Tumor Chemoradiotherapy","status":"RECRUITING","sponsor":"Affiliated Hospital of Nantong University","startDate":"2025-08-01","conditions":["Myelosuppression","Thoracic Neoplasms","Chemoradiotherapy"],"enrollment":30,"completionDate":"2027-12"},{"nctId":"NCT02553460","phase":"PHASE1,PHASE2","title":"Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I","status":"ACTIVE_NOT_RECRUITING","sponsor":"St. Jude Children's Research Hospital","startDate":"2016-01-29","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":50,"completionDate":"2031-10"},{"nctId":"NCT03117751","phase":"PHASE2,PHASE3","title":"Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"St. Jude Children's Research Hospital","startDate":"2017-03-29","conditions":["Acute Lymphoblastic Leukemia","Acute Lymphoblastic Lymphoma"],"enrollment":790,"completionDate":"2028-09-30"},{"nctId":"NCT03568266","phase":"","title":"Pharmacogenomics of Asparaginase Induced Hepatotoxicity","status":"RECRUITING","sponsor":"University of Southern California","startDate":"2018-05-22","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":500,"completionDate":"2026-12-31"},{"nctId":"NCT02101853","phase":"PHASE3","title":"Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2014-12-17","conditions":["Recurrent B Acute Lymphoblastic Leukemia"],"enrollment":669,"completionDate":"2026-09-16"},{"nctId":"NCT02112916","phase":"PHASE3","title":"Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2014-10-04","conditions":["Adult T Acute Lymphoblastic Leukemia","Ann Arbor Stage II Adult Lymphoblastic Lymphoma","Ann Arbor Stage II Childhood Lymphoblastic Lymphoma","Ann Arbor Stage III Adult Lymphoblastic Lymphoma","Ann Arbor Stage III Childhood Lymphoblastic Lymphoma","Ann Arbor Stage IV Adult Lymphoblastic Lymphoma","Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma","Childhood T Acute Lymphoblastic Leukemia"],"enrollment":847,"completionDate":"2026-09-16"},{"nctId":"NCT05034627","phase":"PHASE1","title":"Calaspargase Pegol-Mnkl and Cobimetinib for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"OHSU Knight Cancer Institute","startDate":"2022-08-09","conditions":["Locally Advanced Pancreatic Adenocarcinoma","Metastatic Pancreatic Adenocarcinoma","Stage II Pancreatic Cancer AJCC v8","Stage IIA Pancreatic Cancer AJCC v8","Stage IIB Pancreatic Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8"],"enrollment":15,"completionDate":"2026-10-01"},{"nctId":"NCT02003222","phase":"PHASE3","title":"Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2014-05-19","conditions":["Acute Lymphoblastic Leukemia","B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative"],"enrollment":488,"completionDate":"2026-03-25"},{"nctId":"NCT02883049","phase":"PHASE3","title":"Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2012-02-29","conditions":["B Acute Lymphoblastic Leukemia","B Acute Lymphoblastic Leukemia, BCR-ABL1-Like","Central Nervous System Leukemia","Testicular Leukemia"],"enrollment":5949,"completionDate":"2026-10-03"},{"nctId":"NCT01371981","phase":"PHASE3","title":"Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2011-06-20","conditions":["Acute Myeloid Leukemia","Leukemia Cutis","Myeloid Neoplasm","Myeloid Sarcoma"],"enrollment":1645,"completionDate":"2027-09-30"},{"nctId":"NCT07221656","phase":"","title":"Evaluation of Prolonged Asparaginase Activity Levels After Calaspargase Pegol Administration","status":"NOT_YET_RECRUITING","sponsor":"Mayo Clinic","startDate":"2026-02-01","conditions":["Childhood Acute Lymphoblastic Leukemia","Childhood Lymphoblastic Lymphoma"],"enrollment":20,"completionDate":"2027-12-31"},{"nctId":"NCT07227584","phase":"PHASE2","title":"ALL Backbone in AYAs","status":"NOT_YET_RECRUITING","sponsor":"Dana-Farber Cancer Institute","startDate":"2026-04","conditions":["Acute Lymphoblastic Leukemia","Philadelphia Chromosome-Negative Lymphoblastic Leukemia","Acute Lymphoblastic Leukemia (ALL)","Leukemia"],"enrollment":67,"completionDate":"2035-07-31"},{"nctId":"NCT07059975","phase":"EARLY_PHASE1","title":"UPDATE AML: UPdated Disease Monitoring And Treatment for Enhanced Outcomes for Pediatric AML","status":"RECRUITING","sponsor":"Joanna Yi","startDate":"2025-10-22","conditions":["Acute Myeloid Leukemia","Pediatric AML"],"enrollment":36,"completionDate":"2031-08"},{"nctId":"NCT02879643","phase":"PHASE1","title":"Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy","status":"COMPLETED","sponsor":"Therapeutic Advances in Childhood Leukemia Consortium","startDate":"2017-01-31","conditions":["ALL, Childhood","Lymphoblastic Leukemia, Acute, Childhood","Lymphoblastic Leukemia, Acute"],"enrollment":29,"completionDate":"2024-12-31"},{"nctId":"NCT00136435","phase":"PHASE2","title":"A Study in Adults With Untreated Acute Lymphoblastic Leukemia","status":"COMPLETED","sponsor":"Dana-Farber Cancer Institute","startDate":"2002-06","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":100,"completionDate":"2011-05"},{"nctId":"NCT04501614","phase":"PHASE1,PHASE2","title":"A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia","status":"TERMINATED","sponsor":"Takeda","startDate":"2021-02-24","conditions":["Pediatric Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL)","Ph+ Mixed Phenotype Acute Leukemia (MPAL)","Philadelphia Chromosome-Like ALL (Ph-like ALL)"],"enrollment":11,"completionDate":"2024-07-19"},{"nctId":"NCT07039877","phase":"PHASE2","title":"Efficacy of Low-dose Venetoclax With Itraconazole + TACL for R/R ALL Patients","status":"RECRUITING","sponsor":"Hospital Universitario Dr. Jose E. Gonzalez","startDate":"2025-01-02","conditions":["Acute Lymphobkastic Leukemia","Acute Lymphoblastic Leukaemia Recurrent","Philadelphia Chromosome Negative ALL"],"enrollment":12,"completionDate":"2026-04-30"},{"nctId":"NCT05192889","phase":"PHASE1,PHASE2","title":"Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax","status":"ACTIVE_NOT_RECRUITING","sponsor":"St. Jude Children's Research Hospital","startDate":"2022-08-25","conditions":["Refractory Acute Lymphoblastic Leukemia","Relapsed Acute Lymphoblastic Leukemia"],"enrollment":35,"completionDate":"2027-02"},{"nctId":"NCT01920737","phase":"PHASE2","title":"A Novel \"Pediatric-Inspired\" Regimen With Reduced Myelosuppressive Drugs for Adults (Aged 18-60) With Newly Diagnosed Ph Negative Acute Lymphoblastic Leukemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"Memorial Sloan Kettering Cancer Center","startDate":"2013-08-07","conditions":["Leukemia"],"enrollment":39,"completionDate":"2026-08"},{"nctId":"NCT04546399","phase":"PHASE2","title":"A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)","status":"RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2020-12-17","conditions":["Down Syndrome","Recurrent B Acute Lymphoblastic Leukemia"],"enrollment":461,"completionDate":"2028-06-30"},{"nctId":"NCT03860844","phase":"PHASE2","title":"Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia","status":"TERMINATED","sponsor":"Sanofi","startDate":"2019-08-06","conditions":["Acute Lymphoblastic Leukemia","Acute Myeloid Leukemia"],"enrollment":67,"completionDate":"2023-05-26"},{"nctId":"NCT03564678","phase":"PHASE2","title":"Levocarnitine and Vitamin B Complex in Treating PEG-Asparaginase or Inotuzumab Ozogamicin-Induced Hyperbilirubinemia in Patients With Acute Lymphoblastic Leukemia","status":"TERMINATED","sponsor":"M.D. Anderson Cancer Center","startDate":"2018-05-17","conditions":["Acute Lymphoblastic Leukemia","Hyperbilirubinemia"],"enrollment":10,"completionDate":"2024-10-15"},{"nctId":"NCT07152041","phase":"PHASE3","title":"Newly-diagnosed Pediatric Ph-positive B-ALL Protocol","status":"RECRUITING","sponsor":"Institute of Hematology & Blood Diseases Hospital, China","startDate":"2025-03-28","conditions":["Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+)","Childhood Leukemia, Acute Lymphoblastic"],"enrollment":150,"completionDate":"2030-06"},{"nctId":"NCT06882057","phase":"PHASE2,PHASE3","title":"Newly-diagnosed Low Risk Pediatric B-cell ALL Protocol","status":"RECRUITING","sponsor":"Institute of Hematology & Blood Diseases Hospital, China","startDate":"2025-03-03","conditions":["Acute Lymphoblastic Leukemia ALL","Childhood Leukemia, Acute Lymphoblastic","B Cell Acute Lymphoblastic Leukemia (B-ALL)"],"enrollment":3000,"completionDate":"2033-06"},{"nctId":"NCT06855810","phase":"PHASE2,PHASE3","title":"Newly-diagnosed Pediatric T-cell ALL Protocol","status":"RECRUITING","sponsor":"Institute of Hematology & Blood Diseases Hospital, China","startDate":"2025-03-11","conditions":["Acute Lymphoblastic Leukemia","Childhood Leukemia, Acute Lymphoblastic","T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma"],"enrollment":610,"completionDate":"2031-06"},{"nctId":"NCT03156790","phase":"PHASE2","title":"PK, PD, Safety and Immunogenicity of Spectrila in Adults With Acute B-cell Lymphoblastic Leukaemia","status":"ACTIVE_NOT_RECRUITING","sponsor":"medac GmbH","startDate":"2019-04-26","conditions":["Acute B-Cell Lymphoblastic Leukaemia"],"enrollment":40,"completionDate":"2026-05"},{"nctId":"NCT04440267","phase":"PHASE2","title":"Efficacy of Acute Lymphoblastic Leukemia-Based Therapy in Treating Patients With Acute Leukemia of Ambiguous Lineage","status":"RECRUITING","sponsor":"Institute of Hematology & Blood Diseases Hospital, China","startDate":"2020-07-08","conditions":["Acute Leukemia of Ambiguous Lineage"],"enrollment":50,"completionDate":"2027-12-20"},{"nctId":"NCT02521493","phase":"PHASE3","title":"Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome","status":"ACTIVE_NOT_RECRUITING","sponsor":"Children's Oncology Group","startDate":"2015-12-23","conditions":["Acute Myeloid Leukemia","Down Syndrome","Myelodysplastic Syndrome","Myeloid Leukemia Associated With Down Syndrome","Myeloproliferative Neoplasm"],"enrollment":280,"completionDate":"2026-06-30"},{"nctId":"NCT05660473","phase":"PHASE2","title":"Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia","status":"RECRUITING","sponsor":"Institute of Hematology & Blood Diseases Hospital, China","startDate":"2022-08-01","conditions":["Precursor Cell Lymphoblastic Leukemia-Lymphoma"],"enrollment":100,"completionDate":"2027-12-30"},{"nctId":"NCT06516679","phase":"PHASE2","title":"Efficacy of Risk-Stratified Treatment in Newly Diagnosed Infant Leukemia","status":"RECRUITING","sponsor":"Yonsei University","startDate":"2024-12-11","conditions":["Leukemia, Lymphoid"],"enrollment":40,"completionDate":"2032-12-31"},{"nctId":"NCT03817320","phase":"PHASE1,PHASE2","title":"PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"Therapeutic Advances in Childhood Leukemia Consortium","startDate":"2019-02-12","conditions":["ALL, Childhood","Lymphoblastic Lymphoma, Childhood","Lymphoblastic Leukemia, Acute, Childhood"],"enrollment":24,"completionDate":"2025-06-30"},{"nctId":"NCT05386576","phase":"EARLY_PHASE1","title":"A Study of Venetoclax in Combination With Chemotherapy to Treat Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)","status":"ACTIVE_NOT_RECRUITING","sponsor":"Memorial Sloan Kettering Cancer Center","startDate":"2022-06-16","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":12,"completionDate":"2026-05"},{"nctId":"NCT00476190","phase":"PHASE2","title":"ALL Adult Consortium Trial: Adult ALL Trial","status":"COMPLETED","sponsor":"Dana-Farber Cancer Institute","startDate":"2007-04","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":112,"completionDate":"2020-03"},{"nctId":"NCT06099366","phase":"PHASE2","title":"Treatment of Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia in Children","status":"RECRUITING","sponsor":"Hee Young Ju","startDate":"2024-03-05","conditions":["Lymphoblastic Leukemia in Children"],"enrollment":116,"completionDate":"2033-12-31"},{"nctId":"NCT05827549","phase":"PHASE2","title":"Evaluation of Treatment Efficacy According to Risk Group in Relapsed Childhood Acute Lymphoblastic Leukemia","status":"RECRUITING","sponsor":"Ho Joon Im","startDate":"2024-04-04","conditions":["Acute Lymphoid Leukemia"],"enrollment":90,"completionDate":"2032-12-31"},{"nctId":"NCT02303821","phase":"PHASE1","title":"Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia","status":"COMPLETED","sponsor":"Amgen","startDate":"2015-02-16","conditions":["Acute Lymphoblastic Leukemia (ALL)"],"enrollment":141,"completionDate":"2024-06-28"},{"nctId":"NCT03384654","phase":"PHASE2","title":"A Study to Evaluate the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Participants Greater Than or Equal to (>=)1 and Less Than or Equal to (<=) 30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma","status":"COMPLETED","sponsor":"Janssen Research & Development, LLC","startDate":"2018-05-14","conditions":["Precursor Cell Lymphoblastic Leukemia-Lymphoma"],"enrollment":47,"completionDate":"2022-09-27"},{"nctId":"NCT06034561","phase":"PHASE2","title":"Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia","status":"RECRUITING","sponsor":"Instituto do Cancer do Estado de São Paulo","startDate":"2024-04-01","conditions":["Acute Lymphoblastic Leukemia, in Relapse","Acute Lymphoblastic Leukemia With Failed Remission"],"enrollment":50,"completionDate":"2029-08"},{"nctId":"NCT05959720","phase":"","title":"Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil","status":"RECRUITING","sponsor":"Instituto do Cancer do Estado de São Paulo","startDate":"2023-09-05","conditions":["Acute Lymphoid Leukemia","Minimal Residual Disease","Gene Abnormality","Chemotherapeutic Toxicity"],"enrollment":180,"completionDate":"2030-06"},{"nctId":"NCT00408005","phase":"PHASE3","title":"Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma","status":"COMPLETED","sponsor":"National Cancer Institute (NCI)","startDate":"2007-01-30","conditions":["T Acute Lymphoblastic Leukemia","T Lymphoblastic Lymphoma"],"enrollment":1895,"completionDate":"2025-03-31"},{"nctId":"NCT03643276","phase":"PHASE3","title":"Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017","status":"RECRUITING","sponsor":"Martin Schrappe","startDate":"2018-07-15","conditions":["Acute Lymphoblastic Leukemia, Pediatric"],"enrollment":5000,"completionDate":"2028-07-14"},{"nctId":"NCT01190930","phase":"PHASE3","title":"Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"Children's Oncology Group","startDate":"2010-08-09","conditions":["Acute Lymphoblastic Leukemia","Adult B Lymphoblastic Lymphoma","Ann Arbor Stage I B Lymphoblastic Lymphoma","Ann Arbor Stage II B Lymphoblastic Lymphoma","Childhood B Acute Lymphoblastic Leukemia","Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1","Childhood B Lymphoblastic Lymphoma","Down Syndrome","Hypodiploid B Acute Lymphoblastic Leukemia","Philadelphia Chromosome Positive"],"enrollment":9350,"completionDate":"2028-03-31"},{"nctId":"NCT04043494","phase":"PHASE3","title":"International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma","status":"RECRUITING","sponsor":"University Hospital Muenster","startDate":"2019-08-23","conditions":["Lymphoblastic Lymphoma, Childhood"],"enrollment":683,"completionDate":"2027-11-22"},{"nctId":"NCT02828358","phase":"PHASE2","title":"Azacitidine and Combination Chemotherapy in Treating Infants With Acute Lymphoblastic Leukemia and KMT2A Gene Rearrangement","status":"COMPLETED","sponsor":"National Cancer Institute (NCI)","startDate":"2017-04-01","conditions":["Acute Leukemia of Ambiguous Lineage","B Acute Lymphoblastic Leukemia","Mixed Phenotype Acute Leukemia"],"enrollment":78,"completionDate":"2024-12-31"},{"nctId":"NCT06361329","phase":"PHASE3","title":"Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in Newly Diagnosed ETP-ALL","status":"RECRUITING","sponsor":"First Affiliated Hospital of Zhejiang University","startDate":"2024-04-03","conditions":["ETP-ALL"],"enrollment":81,"completionDate":"2027-03-31"},{"nctId":"NCT04526795","phase":"PHASE1","title":"Fludarabine, Cytarabine, and Pegcrisantaspase for the Treament of Relapsed or Refractory Leukemia","status":"TERMINATED","sponsor":"M.D. Anderson Cancer Center","startDate":"2021-04-09","conditions":["Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive","Recurrent Acute Biphenotypic Leukemia","Recurrent Acute Lymphoblastic Leukemia","Recurrent Acute Myeloid Leukemia","Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive","Recurrent T-Cell Prolymphocytic Leukemia","Refractory Acute Biphenotypic Leukemia","Refractory Acute Lymphoblastic Leukemia","Refractory Acute Myeloid Leukemia","Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive","Refractory T-Cell Prolymphocytic Leukemia"],"enrollment":19,"completionDate":"2024-11-15"},{"nctId":"NCT01228331","phase":"PHASE2,PHASE3","title":"Clofarabine or High-Dose Cytarabine and Pegaspargase in Children with ALL","status":"COMPLETED","sponsor":"Universitätsklinikum Hamburg-Eppendorf","startDate":"2010-10","conditions":["Leukemia"],"enrollment":745,"completionDate":"2024-11-20"},{"nctId":"NCT06676293","phase":"NA","title":"Compassionate Use of Asparaginase and Pembrolizumab Combination Theaapy for Nasopharyngeal Carcinoma","status":"COMPLETED","sponsor":"Chang Gung Memorial Hospital","startDate":"2023-08-01","conditions":["Nasopharyngeal Carcinoma (NPC)"],"enrollment":8,"completionDate":"2024-08-01"},{"nctId":"NCT05557110","phase":"PHASE2","title":"Reduced-dose Chemotherapy Followed by Blinatumomab in Induction Therapy of Newly Diagnosed Non-elderly Ph-B-ALL","status":"COMPLETED","sponsor":"Chen Suning","startDate":"2022-09-08","conditions":["B Acute Lymphoblastic Leukemia"],"enrollment":35,"completionDate":"2024-03-31"},{"nctId":"NCT05501899","phase":"EARLY_PHASE1","title":"Use of Levocarnitine to Reduce Asparaginase Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia","status":"RECRUITING","sponsor":"Children's Hospital of Orange County","startDate":"2023-03-03","conditions":["Acute Lymphoblastic Leukemia","Hepatotoxicity"],"enrollment":20,"completionDate":"2024-12-31"},{"nctId":"NCT05873322","phase":"","title":"Glucose Intolerance and Diabetes Related to Treatment With Steroids and PEG- Asparaginase in Children and Adolescents With ALL and Lymphoma","status":"RECRUITING","sponsor":"Aarhus University Hospital","startDate":"2022-08-30","conditions":["Precursor Cell Lymphoblastic Leukemia-Lymphoma","Drug-Induced Diabetes Mellitus","Impaired Glucose Tolerance","Lymphoma"],"enrollment":100,"completionDate":"2025-12-31"},{"nctId":"NCT01523977","phase":"PHASE1","title":"Everolimus With Multiagent Re-Induction Chemotherapy in Pediatric Patients With ALL","status":"COMPLETED","sponsor":"Dana-Farber Cancer Institute","startDate":"2011-11","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":22,"completionDate":"2018-11"},{"nctId":"NCT00557193","phase":"PHASE3","title":"Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia","status":"COMPLETED","sponsor":"Children's Oncology Group","startDate":"2008-01-15","conditions":["Acute Lymphoblastic Leukemia","Acute Undifferentiated Leukemia","Childhood T Acute Lymphoblastic Leukemia"],"enrollment":218,"completionDate":"2024-06-30"},{"nctId":"NCT02393859","phase":"PHASE3","title":"Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)","status":"COMPLETED","sponsor":"Amgen","startDate":"2015-11-10","conditions":["Leukemia, Acute Lymphoblastic"],"enrollment":111,"completionDate":"2022-11-21"},{"nctId":"NCT06210750","phase":"PHASE2","title":"Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL)","status":"WITHDRAWN","sponsor":"National Cancer Institute (NCI)","startDate":"2024-08-09","conditions":["T Acute Lymphoblastic Leukemia","T Lymphoblastic Lymphoma"],"enrollment":0,"completionDate":"2026-09-22"},{"nctId":"NCT05006040","phase":"EARLY_PHASE1","title":"HCL Single Arm Pilot Study in Treatment of Hyperglycemia of Pediatric ALL","status":"TERMINATED","sponsor":"University of Colorado, Denver","startDate":"2022-05-12","conditions":["High Risk Acute Lymphoblastic Leukemia"],"enrollment":1,"completionDate":"2023-08-01"},{"nctId":"NCT03246750","phase":"PHASE1,PHASE2","title":"B-MAD Chemotherapy in Newly-diagnosed Extranodal NK/ T-cell Lymphoma","status":"COMPLETED","sponsor":"The Thai Lymphoma Study Group","startDate":"2019-01-30","conditions":["Extranodal NK/T-cell Lymphoma"],"enrollment":34,"completionDate":"2024-04-10"},{"nctId":"NCT06336395","phase":"PHASE2","title":"Ma-Spore ALL 2020 Study","status":"RECRUITING","sponsor":"National University Hospital, Singapore","startDate":"2020-03-04","conditions":["B Lymphoblastic Leukemia"],"enrollment":500,"completionDate":"2030-03"},{"nctId":"NCT00381680","phase":"PHASE3","title":"Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia","status":"COMPLETED","sponsor":"Children's Oncology Group","startDate":"2007-03","conditions":["B-cell Childhood Acute Lymphoblastic Leukemia","L1 Childhood Acute Lymphoblastic Leukemia","L2 Childhood Acute Lymphoblastic Leukemia","Intermediate Risk Recurrent Childhood Acute Lymphoblastic Leukemia"],"enrollment":275,"completionDate":""},{"nctId":"NCT03267030","phase":"PHASE2","title":"Asparaginase Encapsulated in Erythrocytes for Patients With ALL and Hypersensitivity to PEG-asparaginase","status":"COMPLETED","sponsor":"Birgitte Klug Albertsen","startDate":"2017-08-23","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":55,"completionDate":"2020-10-22"},{"nctId":"NCT02013167","phase":"PHASE3","title":"Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)","status":"TERMINATED","sponsor":"Amgen","startDate":"2014-01-03","conditions":["Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia"],"enrollment":405,"completionDate":"2017-03-14"},{"nctId":"NCT03599960","phase":"PHASE2","title":"Combination Chemotherapy in Patients With Newly Diagnosed BPDCN","status":"UNKNOWN","sponsor":"Centre Hospitalier Universitaire de Besancon","startDate":"2019-05-02","conditions":["Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)"],"enrollment":26,"completionDate":"2024-11"},{"nctId":"NCT04843514","phase":"","title":"TDM of Asparaginase in ALL2008","status":"COMPLETED","sponsor":"Aarhus University Hospital","startDate":"2021-04-01","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":765,"completionDate":"2024-01-31"},{"nctId":"NCT04843150","phase":"","title":"Pharmacokinetics and Immunogenicity of the First Doses of PEG-Asparaginase -An ALLTogether Pilot Study","status":"COMPLETED","sponsor":"Aarhus University Hospital","startDate":"2020-07-01","conditions":["Acute Lymphoblastic Leukemia"],"enrollment":320,"completionDate":"2023-10-01"},{"nctId":"NCT01186328","phase":"PHASE1","title":"EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)","status":"TERMINATED","sponsor":"Therapeutic Advances in Childhood Leukemia Consortium","startDate":"2010-08-24","conditions":["Lymphoblastic Leukemia, Acute","Lymphoblastic Leukemia, Acute, Childhood","Leukemia, Lymphoblastic, Acute, T Cell","Leukemia, Lymphoblastic, Acute"],"enrollment":6,"completionDate":"2012-01-10"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"pivotalTrials":["NCT04145531"],"administration":{"route":"Intramuscular","formulation":"Injection","formulations":[{"form":"INJECTION","route":"INTRAMUSCULAR","productName":"Rylaze"}]},"crossReferences":{"MMSL":"4222","NDDF":"002673","UNII":"G4FQ3CKY5R","VANDF":"4017974","RXNORM":"1156","UMLSCUI":"C0003993","chemblId":"CHEMBL2108989","ChEMBL_ID":"CHEMBL2108989","DRUGBANK_ID":"DB00023","PUBCHEM_CID":"5460875","SNOMEDCT_US":"18811003","MESH_DESCRIPTOR_UI":"D001215"},"formularyStatus":[],"_enricherVersion":"v2","developmentCodes":[],"ownershipHistory":[{"period":"1994-","companyName":"Merck","relationship":"Original Developer"}],"pharmacokinetics":{"source":"FDA label","halfLife":"18.2 hours"},"publicationCount":5759,"therapeuticAreas":["Oncology"],"_revenueScrapedAt":"2026-03-31 13:40:32.077115+00","atcClassification":{"source":"DrugCentral","atcCode":"L01XX02","allCodes":["L01XX02"]},"biosimilarFilings":[],"originalDeveloper":"Merck","recentPublications":[],"companionDiagnostics":[],"genericManufacturerList":[],"status":"approved","companyName":"Merck & Co.","companyId":"merck","modality":"Enzyme","firstApprovalDate":"1994","enrichmentLevel":4,"visitCount":0,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2021-06-30T00:00:00.000Z","mah":"JAZZ PHARMS","brand_name_local":null,"application_number":"BLA761179"},{"country_code":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"AU","regulator":"TGA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"CH","regulator":"Swissmedic","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"NO","regulator":"NoMA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"IS","regulator":"IMA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"NZ","regulator":"Medsafe","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"AT","regulator":"AGES","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"BE","regulator":"FAMHP","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"EU","regulator":"EMA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":"EMEA/H/C/002661"},{"country_code":"GB","regulator":"MHRA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"BG","regulator":"BDA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"HR","regulator":"HALMED","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"CY","regulator":"PHS","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"CZ","regulator":"SUKL","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"DK","regulator":"DKMA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"EE","regulator":"SAM","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"FI","regulator":"Fimea","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"FR","regulator":"ANSM","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"DE","regulator":"BfArM","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"GR","regulator":"EOF","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"HU","regulator":"OGYEI","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"IE","regulator":"HPRA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"IT","regulator":"AIFA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"LV","regulator":"ZVA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"LT","regulator":"VVKT","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"LU","regulator":"MS","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"MT","regulator":"MMA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"NL","regulator":"MEB","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"PL","regulator":"URPL","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"PT","regulator":"Infarmed","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"RO","regulator":"ANMDMR","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"SK","regulator":"SIDC","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"SI","regulator":"JAZMP","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"ES","regulator":"AEMPS","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"SE","regulator":"MPA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Spectrila","application_number":null},{"country_code":"BR","regulator":"ANVISA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"MX","regulator":"COFEPRIS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AR","regulator":"ANMAT","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TR","regulator":"TITCK","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IN","regulator":"CDSCO","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TH","regulator":"FDA-TH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"MY","regulator":"NPRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"PH","regulator":"FDA-PH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"CO","regulator":"INVIMA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"ZA","regulator":"SAHPRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TW","regulator":"TFDA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"HK","regulator":"DH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null}],"trialStats":{"total":12,"withResults":3},"validation":{"fieldsValidated":4,"lastValidatedAt":"2026-04-20T03:35:49.682064+00:00","fieldsConflicting":0,"overallConfidence":0.95},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}