NCT00671034

Calaspargase Pegol or Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

Completed Phase 3 Results posted Last updated 27 April 2021

What this trial tests

Phase 3 trial testing Calaspargase Pegol-mknl in Acute Lymphoblastic Leukemia in 166 participants. Completed in 31 March 2021.

Timeline

21 July 2008

Primary endpoint
1 February 2011

31 March 2021

Quick facts

Lead sponsor	Children's Oncology Group
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	166
Start date	21 July 2008
Primary completion	1 February 2011
Estimated completion	31 March 2021
Sites	27 locations across United States

Drugs / interventions tested

• Calaspargase Pegol-mknl
• Cyclophosphamide
• Cytarabine
• Daunorubicin Hydrochloride (daunorubicin) — full drug profile →
• Dexamethasone (dexamethasone) — full drug profile →
• Doxorubicin Hydrochloride — full drug profile →
• Laboratory Biomarker Analysis
• Mercaptopurine
• Methotrexate
• Pegaspargase
• Pharmacological Study
• Prednisone (prednisone) — full drug profile →
• Radiation Therapy
• Thioguanine
• Vincristine Sulfate

Conditions studied

• Acute Lymphoblastic Leukemia — all drugs for Acute Lymphoblastic Leukemia →
• Adult B Acute Lymphoblastic Leukemia — all drugs for Adult B Acute Lymphoblastic Leukemia →
• Childhood B Acute Lymphoblastic Leukemia — all drugs for Childhood B Acute Lymphoblastic Leukemia →

Sponsor

Children's Oncology Group — full company profile →

Who can join

Adults 2 to 30, any sex, with Acute Lymphoblastic Leukemia or Adult B Acute Lymphoblastic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetics (PK) (Half-life of SC-PEG E. Coli L-asparaginase (EZN-2285) Compared to Pegaspargase During Induction and Consolidation Therapy) Primary · Post Day 29 of Induction and Post Day 22 of Consolidation

Mean half-life of plasma asparaginase during consolidation and Induction; half-life is defined as the time taken for drug concentration to decrease by half.

Asparaginase half-life during Consolidation

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	415.8	± 148.51
Arm II ( Calaspargase Pegol 2500)	355.9	± 133.0
Arm III (Pegaspargase 2500)	117.2	± 49.36

Asparaginase half-life during Induction

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	305.1	± 98.33
Arm II ( Calaspargase Pegol 2500)	321.5	± 118.22
Arm III (Pegaspargase 2500)	126.9	± 50.51

Pharmacodynamics (PD) Secondary · Day 29 of consolidation and induction

Plasma Asparaginase Concentration During consolidation and induction.

Plasma Asparaginase Concentration- Consolidation

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	575.9	± 233.91
Arm II (Calaspargase Pegol 2500)	617.2	± 321.41
Arm III (Pegaspargase 2500)	562.1	± 296.82

Plasma Asparaginase Concentration- Induction

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	271.6	± 118.17
Arm II (Calaspargase Pegol 2500)	339.6	± 126.83
Arm III (Pegaspargase 2500)	72.8	± 47.94

Percentage of Participants With Minimal Residual Disease (MRD)<0.01% at the End of Induction Secondary · End of induction (Day 29)

Percentage of participants with Negative MRD (MRD\<0.01%).

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	65.2	52.4 – 76.5
Arm II (Calaspargase Pegol 2500)	81	65.9 – 91.4
Arm III (Pegaspargase 2500)	72.5	58.3 – 84.1

Percentage of Participants With Complete Remission at the End of Induction Secondary · End of induction (Day 29)

Complete Remission (CR) rate; where CR is defined as M1 marrow (\< 5% lymphoblasts in the bone marrow)

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	92.4	83.2 – 97.5
Arm II (Calaspargase Pegol 2500)	97.6	87.4 – 99.9
Arm III (Pegaspargase 2500)	94.1	83.8 – 98.8

Percentage of Participants With Event-free Survival (EFS) Secondary · 5 Years

Percentage of participants who were event free. Event Free Probability defined as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignant neoplasm, remission death) or date of last contact for subjects who are event-free.

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	72.35	60.98 – 83.72
Arm II (Calaspargase Pegol 2500)	80.8	68.3 – 93.3
Arm III (Pegaspargase 2500)	79.34	67.56 – 91.12

Asparaginase Level Secondary · Days 4, 15, 22 and 29 of Induction

The proportion of patients with an asparaginase level of at least 0.1 IU/mL and the proportion with at least 0.4 IU/mL on Days 4, 15, 22 and 29 of Induction compared to Oncaspar

Level at least 0.1 IU/mL day 4

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	0	0.0 – 8.2
Arm II (Calaspargase Pegol 2500)	0	0.0 – 8.8
Arm III (Pegaspargase 2500)	0	0.0 – 5.8

Level at least 0.1 IU/mL day 15

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	98.4	91.3 – 100.0
Arm II (Calaspargase Pegol 2500)	100	91.2 – 100
Arm III (Pegaspargase 2500)	100	98.1 – 100

Level at least 0.1 IU/mL day 22

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	98.2	78.1 – 98.5
Arm II (Calaspargase Pegol 2500)	100	91.2 – 100
Arm III (Pegaspargase 2500)	95.1	77.9 – 97.4

Level at least 0.1 IU/mL day 29

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	94.9	80.1 – 96.4
Arm II (Calaspargase Pegol 2500)	95.0	83.1 – 99.4
Arm III (Pegaspargase 2500)	28.6	15.3 – 43.7

Level at least 0.4 IU/mL day 4

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	0	0.0 – 8.2
Arm II (Calaspargase Pegol 2500)	0	0.0 – 8.8
Arm III (Pegaspargase 2500)	0	0.0 – 5.8

Level at least 0.4 IU/mL day 15

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	75.8	63.3 – 85.8
Arm II (Calaspargase Pegol 2500)	95.0	83.1 – 99.4
Arm III (Pegaspargase 2500)	93.0	80.9 – 98.5

Level at least 0.4 IU/mL day 22

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	37.5	22.3 – 47.0
Arm II (Calaspargase Pegol 2500)	62.5	45.8 – 77.3
Arm III (Pegaspargase 2500)	14.6	5.3 – 27.9

Level at least 0.4 IU/mL day 29

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	13.6	5.7 – 23.9
Arm II (Calaspargase Pegol 2500)	27.5	14.6 – 43.9
Arm III (Pegaspargase 2500)	0	0.0 – 8.2

Plasma and CSF Concentrations of Asparagine in ug/ml Secondary · 25 Days Post-dose (Day 29)

The plasma and CSF concentrations of asparagine in ug/ml after administration of EZN-2285 compared to Oncaspar.

CSF asparagine concentration (ug/mL)

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	0.2	± 0.108
Arm II (Calaspargase Pegol 2500)	0.19	± 0.086
Arm III (Pegaspargase 2500)	0.26	± 0.26

Plasma asparagine concentration (ug/mL)

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	0.2	± 0.784
Arm II (Calaspargase Pegol 2500)	0.25	± 1.231
Arm III (Pegaspargase 2500)	0.83	± 2.195

Immunogenicity Secondary · 25 Days Post-dose (Day 29)

Number of Patients with Positive Immunogenicity tests

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	2
Arm II (Calaspargase Pegol 2500)	2
Arm III (Pegaspargase 2500)	4

Toxicities During Post Induction Intensification Therapy (All Grades) Secondary · Up to 5 years

The calculation of AE incidence will be based on the number of patients per AE category. For each patient who has multiple AEs classified to the same category, that patient will be tabulated under the worst toxicity grade for that AE category. The incidence of AEs will be tabulated by treatment arm and by organ class. Special attention will be paid to hypersensitivity, pancreatitis, coagulopathy, infection, neurologic dysfunction and thromboembolic events.

Alergic Reaction - Consolidation

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	20.4
Arm II (Calaspargase Pegol 2500)	27.3
Arm III (Pegaspargase 2500)	23.3

Alergic Reaction - Delayed Intensification I

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	4.4
Arm II (Calaspargase Pegol 2500)	0.0
Arm III (Pegaspargase 2500)	0.0

Alergic Reaction - Interim Maintenance I

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	0.0
Arm II (Calaspargase Pegol 2500)	0.0
Arm III (Pegaspargase 2500)	2.1

CNS - Consolidation

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	0.0
Arm II (Calaspargase Pegol 2500)	0.0
Arm III (Pegaspargase 2500)	0.0

CNS - Delayed Intensification I

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	0.0
Arm II (Calaspargase Pegol 2500)	3.8
Arm III (Pegaspargase 2500)	2.6

CNS - Interim Maintenance I

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	0.0
Arm II (Calaspargase Pegol 2500)	0.0
Arm III (Pegaspargase 2500)	0.0

Hyperbilirubinemia - Consolidation

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	53.1
Arm II (Calaspargase Pegol 2500)	45.5
Arm III (Pegaspargase 2500)	30.2

Hyperbilirubinemia - Delayed Intensification I

Group	Value	95% CI
Arm I (Calaspargase Pegol 2100)	28.9
Arm II (Calaspargase Pegol 2500)	38.5
Arm III (Pegaspargase 2500)	10.5

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm I (Calaspargase Pegol 2100)

Serious: 54/69 (78%)

Deaths: —

Arm II (Calaspargase Pegol 2500)

Serious: 34/42 (81%)

Deaths: —

Arm III (Pegaspargase 2500)

Serious: 32/54 (59%)

Deaths: —

Serious adverse events (108 terms)

Reaction	System	Arm I (Calaspargase Pegol …	Arm II (Calaspargase Pegol…	Arm III (Pegaspargase 2500)
Hyperglycemia	Metabolism and nutrition disorders	—	—	—
Infections and infestations - Other, specify	Infections and infestations	—	—	—
Anaphylaxis	Immune system disorders	—	—	—
Blood bilirubin increased	Investigations	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Pancreatitis	Gastrointestinal disorders	—	—	—
Serum amylase increased	Investigations	—	—	—
Lipase increased	Investigations	—	—	—
Hypotension	Vascular disorders	—	—	—
Platelet count decreased	Investigations	—	—	—
Hypertriglyceridemia	Metabolism and nutrition disorders	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—
Thromboembolic event	Vascular disorders	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—
Death NOS	General disorders	—	—	—
Fibrinogen decreased	Investigations	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—
Oral pain	Gastrointestinal disorders	—	—	—
Activated partial thromboplastin time prolonged	Investigations	—	—	—
Cholesterol high	Investigations	—	—	—
INR increased	Investigations	—	—	—

Other adverse events (163 terms — click to expand)

Reaction	System	Arm I (Calaspargase Pegol …	Arm II (Calaspargase Pegol…	Arm III (Pegaspargase 2500)
Neutrophil count decreased	Investigations	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—
Infections and infestations - Other, specify	Infections and infestations	—	—	—
Platelet count decreased	Investigations	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—
White blood cell decreased	Investigations	—	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—	—
Mucositis oral	Gastrointestinal disorders	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Hyperkalemia	Metabolism and nutrition disorders	—	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—
Lung infection	Infections and infestations	—	—	—
Blood bilirubin increased	Investigations	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—
GGT increased	Investigations	—	—	—
Lipase increased	Investigations	—	—	—
Headache	Nervous system disorders	—	—	—
Oral pain	Gastrointestinal disorders	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Fever	General disorders	—	—	—
Pain	General disorders	—	—	—
Enterocolitis infectious	Infections and infestations	—	—	—
Weight loss	Investigations	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Tumor lysis syndrome	Metabolism and nutrition disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Lymphocyte count decreased	Investigations	—	—	—
Hyperuricemia	Metabolism and nutrition disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—

Most-reported serious reactions: Hyperglycemia, Infections and infestations - Other, specify, Anaphylaxis, Blood bilirubin increased, Abdominal pain, Pancreatitis, Serum amylase increased, Lipase increased.

Data from ClinicalTrials.gov NCT00671034 adverse events section.

Sponsor's own description

This randomized clinical trial is studying giving calaspargase pegol together with combination chemotherapy to see how well it works compared with giving pegaspargase together with combination chemotherapy in treating younger patients with newly diagnosed high-risk acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.
   Maese L, Rau RE. · · 2022 · cited 51× · PMID 35844739 · DOI 10.3389/fped.2022.902117
2. Plasma asparaginase activity and asparagine depletion in acute lymphoblastic leukemia patients treated with pegaspargase on Children's Oncology Group AALL07P4^.
   Schore RJ, Devidas M, Bleyer A, Reaman GH, et al · · 2019 · cited 35× · PMID 30626253 · DOI 10.1080/10428194.2018.1542146
3. Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children's oncology group (COG) clinical trials.
   Burke MJ, Devidas M, Maloney K, Angiolillo A, et al · · 2018 · cited 32× · PMID 29115886 · DOI 10.1080/10428194.2017.1397658
4. FDA approvals for pediatric cancer indications using children's oncology group associated trials data.
   Macy ME, Fox E, Weigel BJ, Foster JH, et al · · 2026 · cited 1× · PMID 41885402 · DOI 10.1093/jnci/djag089