NCT02472145

An Efficacy and Safety Study of Decitabine (DACOGEN) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus Decitabine (DACOGEN) Alone in Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy

Completed Phase 2, PHASE3 Results posted Last updated 19 March 2019

What this trial tests

Phase 2, PHASE3 trial testing Decitabine 20 mg/m^2 in Leukemia, Myeloid, Acute in 326 participants. Completed in 25 January 2018.

Timeline

4 August 2015

Primary endpoint
25 January 2018

25 January 2018

Quick facts

Lead sponsor	Janssen Research & Development, LLC
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	326
Start date	4 August 2015
Primary completion	25 January 2018
Estimated completion	25 January 2018
Sites	81 locations across France, Russia, Belgium, Sweden, Taiwan, United Kingdom, Germany, Israel

Drugs / interventions tested

• Decitabine 20 mg/m^2 — full drug profile →
• Talacotuzumab 9 mg/kg — full drug profile →

Conditions studied

• Leukemia, Myeloid, Acute — all drugs for Leukemia, Myeloid, Acute →

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

65 and older, any sex, with Leukemia, Myeloid, Acute. 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.

Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment Primary · Approximately up to 2.5 years

Complete response rate defined as percentage of participants who achieved complete response as per modified International Working Group (IWG) criteria. CR: Bone marrow blasts less than (\<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (\>)1.0\*10\^9/liter (L) (1000/micro liter \[mcL\]); platelet count \>100\*10\^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.

Group	Value	95% CI
Part B: Decitabine (Alone)	11.9
Part B: Decitabine + JNJ-56022473	16.6

Part B: Overall Survival Primary · Approximately up to 2.5 years

Overall Survival (OS) was defined as the time from the date of randomization to date of death from any cause. Median Overall Survival was estimated by using the Kaplan-Meier method. This endpoint is reported here for Part B only as per the planned analysis.

Group	Value	95% CI
Part B: Decitabine (Alone)	7.26	6.47 – 8.64
Part B: Decitabine + JNJ-56022473	5.36	4.27 – 7.95

Part B: Event-free Survival (EFS) Based on Investigator Assessment Secondary · Approximately up to 2.5 years

EFS defined as time from randomization to treatment failure, relapse from CR/CRi, or death from any cause, whichever occurs first, per modified IWG criteria. Treatment failure: \>25% absolute increase in the bone marrow blast count from baseline to present assessment (example, 20% to 46%) on bone marrow aspirate (or biopsy in case of dry tap); Relapse: Bone marrow blasts greater than equal to (\>=)5%; reappearance of blasts in blood; or development of extramedullary disease; CR: Bone marrow blasts \<5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil c

Group	Value	95% CI
Part B: Decitabine (Alone)	6.24	4.96 – 6.83
Part B: Decitabine + JNJ-56022473	4.50	3.61 – 6.74

Part B: Percentage of Participants Who Achieved CR and CRi (Overall Response Rate) Secondary · Approximately up to 2.5 years

Percentage of participants who achieved CR and CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (\<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (\>)1.0 \*10\^9/liter (L) (1000/ mcL); platelet count \>100 \*10\^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts \<5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia \<1.0\*10\^9/L (1000/mcL) or thrombocytopenia \<100\*10\^9/L (100 000/mcL); independence of red cell transfusions. This end

Group	Value	95% CI
Part B: Decitabine (Alone)	20.1
Part B: Decitabine + JNJ-56022473	26.8

Part B: Percentage of Participants With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi) Secondary · Approximately 2.5 years

Percentage of participants who achieved CR plus MRD-negative CRi were reported. MRD negativity defined as \<1 blast or leukemic stem cell in 10,000 leukocytes (MRD level \<10\^4).CR: Bone marrow blasts less than (\<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (\>)1.0\*10\^9/liter (L) (1000/mcL); platelet count \>100\*10\^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts \<5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia \<1.0\*10\^9/L (100

Group	Value	95% CI
Part B: Decitabine (Alone)	13.8
Part B: Decitabine + JNJ-56022473	21.3

Part B: Time to Best Response Secondary · Approximately 2.5 years

Time to best response is calculated as the time from the randomization date to the first documented date for the best response for participants who achieved CR or CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (\<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (\>)1.0 \*10\^9/liter (L) (1000/mcL); platelet count \>100\*10\^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts \<5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia \<1.0\*10

Group	Value	95% CI
Part B: Decitabine (Alone)	16.71	7.1 – 41.6
Part B: Decitabine + JNJ-56022473	18.14	7.3 – 68.4

Part B: Duration of Response (DOR) Based on Investigator Assessment Secondary · Approximately 2.5 years

DOR defined as number of weeks from documented best response (CR or CRi) for participants who achieved CR or CRi to relapse, death due to relapse, date of censoring. As per modified IWG criteria: CR: Bone marrow blasts \<5 %; absence of blasts with Auer rods; absence of extramedullary disease;absolute neutrophil count \>1.0\*10\^9/L (1000/mcL); platelet count \>100\*10\^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts \<5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia \<1.0\* 10\^9/L (1000/mcL) or thrombocytopenia \

Group	Value	95% CI
Part B: Decitabine (Alone)	23.71	15.43 – NA
Part B: Decitabine + JNJ-56022473	NA	29.86 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Throughout the study (Up to 2.5 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A: Decitabine + JNJ-56022473

Serious: 9/10 (90%)

Deaths: 10/10

Part B: Decitabine (Alone)

Serious: 120/165 (73%)

Deaths: 101/159

Part B: Decitabine + JNJ-56022473

Serious: 126/147 (86%)

Deaths: 99/157

Serious adverse events (227 terms)

Reaction	System	Part A: Decitabine + JNJ-5…	Part B: Decitabine (Alone)	Part B: Decitabine + JNJ-5…
Febrile Neutropenia	Blood and lymphatic system disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Pyrexia	General disorders	—	—	—
Sepsis	Infections and infestations	—	—	—
Multiple Organ Dysfunction Syndrome	General disorders	—	—	—
Septic Shock	Infections and infestations	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
General Physical Health Deterioration	General disorders	—	—	—
Urinary Tract Infection	Infections and infestations	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Atrial Fibrillation	Cardiac disorders	—	—	—
Cardiac Arrest	Cardiac disorders	—	—	—
Sudden Death	General disorders	—	—	—
Lung Infection	Infections and infestations	—	—	—
Respiratory Tract Infection	Infections and infestations	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Syncope	Nervous system disorders	—	—	—
Acute Kidney Injury	Renal and urinary disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Acute Myocardial Infarction	Cardiac disorders	—	—	—
Tachycardia	Cardiac disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Chills	General disorders	—	—	—

Other adverse events (111 terms — click to expand)

Reaction	System	Part A: Decitabine + JNJ-5…	Part B: Decitabine (Alone)	Part B: Decitabine + JNJ-5…
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Pyrexia	General disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Oedema Peripheral	General disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—
Chills	General disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Febrile Neutropenia	Blood and lymphatic system disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypotension	Vascular disorders	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—
Weight Decreased	Investigations	—	—	—
Headache	Nervous system disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Pain in Extremity	Musculoskeletal and connective tissue disorders	—	—	—
Tachycardia	Cardiac disorders	—	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Atrial Fibrillation	Cardiac disorders	—	—	—
Urinary Tract Infection	Infections and infestations	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—

Most-reported serious reactions: Febrile Neutropenia, Pneumonia, Pyrexia, Sepsis, Multiple Organ Dysfunction Syndrome, Septic Shock, Anaemia, General Physical Health Deterioration.

Data from ClinicalTrials.gov NCT02472145 adverse events section.

Sponsor's own description

The primary objective of study Part A is to assess the safety of talacotuzumab (formerly CSL362) monotherapy and confirm the recommended Phase 2 dose (RP2D) in participants with acute myeloid leukemia (AML) for whom experimental therapy is appropriate. The primary objective of study Part B are to assess complete response (CR) rate and overall survival (OS) in participants with AML who are not eligible for intense induction chemotherapy and who are randomly assigned to receive decitabine plus talacotuzumab at the RP2D or decitabine alone.

Publications & conference data

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

1. Targeting cancer stem cell pathways for cancer therapy.
   Yang L, Shi P, Zhao G, Xu J, et al · · 2020 · cited 1354× · PMID 32296030 · DOI 10.1038/s41392-020-0110-5
2. Biology and relevance of human acute myeloid leukemia stem cells.
   Thomas D, Majeti R. · · 2017 · cited 357× · PMID 28159741 · DOI 10.1182/blood-2016-10-696054
3. Antibodies to watch in 2017.
   Reichert JM. · · 2017 · cited 194× · PMID 27960628 · DOI 10.1080/19420862.2016.1269580
4. Small Molecule NF-κB Pathway Inhibitors in Clinic.
   Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
5. Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia.
   Tasian SK, Kenderian SS, Shen F, Ruella M, et al · · 2017 · cited 144× · PMID 28246194 · DOI 10.1182/blood-2016-08-736041
6. CD123 as a Therapeutic Target in the Treatment of Hematological Malignancies.
   Testa U, Pelosi E, Castelli G. · · 2019 · cited 114× · PMID 31547472 · DOI 10.3390/cancers11091358
7. Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.
   Zeng Z, Fu M, Hu Y, Wei Y, et al · · 2023 · cited 93× · PMID 37853437 · DOI 10.1186/s12943-023-01877-w
8. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.
   Zhao A, Zhou H, Yang J, Li M, et al · · 2023 · cited 81× · PMID 36797244 · DOI 10.1038/s41392-023-01342-6