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.
Title
- Brief Title: 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
- Official Title: A Randomized Phase 2/3 Study of DACOGEN® (Decitabine) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus DACOGEN (Decitabine) Alone in Patients With AML Who Are Not Candidates for Intensive Chemotherapy
Clinical Trial IDs
- ORG STUDY ID:
CR107273
- SECONDARY ID:
56022473AML2002
- SECONDARY ID:
2015-001611-12
- NCT ID:
NCT02472145
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Decitabine 20 mg/m^2 | DACOGEN | Decitabine |
Talacotuzumab 9 mg/kg | CSL362 | Decitabine plus Talacotuzumab |
Purpose
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.
Detailed Description
This is a 2-part, open-label, multicenter, Phase 2/3 study conducted in participants with AML
who are suitable for experimental therapy (Part A) and in participants with untreated AML who
are not eligible for intense induction chemotherapy or hematopoeitic stem cell
transplantation (HSCT) (Part B). In Study Part A, the safety, pharmacokinetic (PK) and
pharmacodynamic (PD) profile will be assessed to confirm the RP2D of 9 milligram per kilogram
(mg/kg) talacotuzumab. In Study Part B, participants will be randomized in a 1:1 ratio into
either decitabine + talacotuzumab (arm 1) or decitabine alone (arm 2). Blood and bone marrow
sampling will be done in Part A and B for disease assessment, PK, PD, and biomarkers will be
collected in all participants. Safety will be monitored throughout the study.
Trial Arms
Name | Type | Description | Interventions |
---|
Decitabine plus Talacotuzumab | Experimental | Part A: For Cycle 1 of Part A, participants will receive talacotuzumab on Day 1. Starting from Cycle 2 of Part A, participants may receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle.
Part B Arm 1: Participants will receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle. | - Decitabine 20 mg/m^2
- Talacotuzumab 9 mg/kg
|
Decitabine | Active Comparator | Participants in Part B Arm 2 will receive decitabine on Day 1,2, 3, 4 and 5 of a 28-day cycle. | |
Eligibility Criteria
Inclusion Criteria:
- De novo or secondary acute myeloid leukemia (AML) (post myelodysplastic syndrome [MDS]
or myeloproliferative neoplasm [MPN] or after leukemogenic chemotherapy) according to
WHO 2008 criteria
For Part A:
- Participants With AML: treatment naive or relapsed for whom experimental therapy is
appropriate (as assessed by their treating physician)
For Part B:
- Greater than or equal to (>=) 75 years of age or >= 65 up to 75 years of age and have
at least one of the following: congestive heart failure or ejection fraction less than
or equal to (<=) 50 percent; creatinine greater than (>) 2 milligram per deciliter
(mg/dL); dialysis or prior renal transplant; documented pulmonary disease with lung
diffusing capacity for carbon monoxide (DLCO) <= 65 percent of expected, or forced
expiratory volume in 1 second (FEV1) <= 65 percent of expected or dyspnea at rest
requiring oxygen; eastern cooperative oncology group (ECOG) performance status of 2;
prior or current malignancy that does not require concurrent treatment; unresolved
infection; comorbidity that, in the Investigator's opinion, makes the participant
unsuitable for intensive chemotherapy and must be documented and approved by the
Sponsor before randomization
- Previously untreated AML (except: emergency leukopheresis and/or hydroxyurea during
the screening phase to control hyperleukocytosis but must be discontinued at least one
day prior to start of study therapy)
- Not eligible for an allogeneic hematopoietic stem cell transplantation
- ECOG Performance Status score of 0, 1 or 2
- A woman must be either: Not of childbearing potential: postmenopausal (more than [>]
45 years of age with amenorrhea for at least 12 months; If, of childbearing potential
must be practicing a highly effective method of birth control
- A woman of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [beta-hCG]) or urine pregnancy test at screening
- A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control eg, either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for at least
3 months after last study treatment
Exclusion Criteria:
- Acute promyelocytic leukemia with t(15;17), or its molecular equivalent (PML-RARalpha)
- For Part B only: Known leukemic involvement or clinical symptoms of leukemic
involvement of the central nervous system
- Participants who received prior treatment with a hypomethylating agent
- For Part A only: Participants who did not recover from all clinically significant
toxicities (excluding alopecia and hematologic toxicities) of any previous surgery,
radiotherapy, targeted therapy, or chemotherapy to less than or equal to Grade 1
- Any uncontrolled active systemic infection that requires treatment with intravenous
(IV) antibiotics
- A history of human immunodeficiency virus (HIV) antibody positive or tests positive
for HIV if tested at screening
- Active systemic hepatitis infection requiring treatment or other clinically active
liver disease
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 65 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment |
Time Frame: | Approximately up to 2.5 years |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Part B: Event-free Survival (EFS) Based on Investigator Assessment |
Time Frame: | Approximately up to 2.5 years |
Safety Issue: | |
Description: | 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 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 <100*10^9/L (100 000/mcL); independence of red cell transfusions. Endpoint reported is for Part B only as per planned analysis. |
Measure: | Part B: Percentage of Participants Who Achieved CR and CRi (Overall Response Rate) |
Time Frame: | Approximately up to 2.5 years |
Safety Issue: | |
Description: | 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 endpoint is reported here for Part B only as per the planned analysis. |
Measure: | Part B: Percentage of Participants With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi) |
Time Frame: | Approximately 2.5 years |
Safety Issue: | |
Description: | 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 (1000/mcL) or thrombocytopenia <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. |
Measure: | Part B: Time to Best Response |
Time Frame: | Approximately 2.5 years |
Safety Issue: | |
Description: | 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*10^9/L (1000/mcL) or thrombocytopenia <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. |
Measure: | Part B: Duration of Response (DOR) Based on Investigator Assessment |
Time Frame: | Approximately 2.5 years |
Safety Issue: | |
Description: | 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 <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. |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Janssen Research & Development, LLC |
Trial Keywords
- Leukemia, myeloid, acute
- DACOGEN
- Decitabine
- JNJ-56022473
- CLS362
Last Updated
March 19, 2019