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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

NCT02472145

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

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

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
Decitabine 20 mg/m^2DACOGENDecitabine plus Talacotuzumab
Talacotuzumab 9 mg/kgCSL362Decitabine 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

NameTypeDescriptionInterventions
Decitabine plus TalacotuzumabExperimentalPart 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
DecitabineActive ComparatorParticipants in Part B Arm 2 will receive decitabine on Day 1,2, 3, 4 and 5 of a 28-day cycle.
  • Decitabine 20 mg/m^2

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:Complete Response Rate
Time Frame:Disease assessment will continue until treatment failure or relapse or clinical cut-off (Approximately up to 4 years after first participant enrollment)
Safety Issue:
Description:Percentage of participants reaching complete response (CR).

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Disease assessment will continue until treatment failure or relapse or clinical cut-off (Approximately up to 4 years after first participant enrollment)
Safety Issue:
Description:Percentage of participants achieving CR (complete response) or CRi (complete response with incomplete recovery).
Measure:Event Free Survival (EFS)
Time Frame:Approximately up to 4 years after first participant enrollment
Safety Issue:
Description:Event free survival will be defined as the time from randomization to treatment failure, relapse from CR or CRi, or death of any cause, whichever occurs first.
Measure:Relapse-free survival (RFS)
Time Frame:Approximately up to 4 years after first participant enrollment
Safety Issue:
Description:For participants who achieved CR or CRi, time from achieving CR or CRi to relapse or death from any cause.
Measure:Number of Participants With Adverse Event
Time Frame:Approximately up to 4 years after first participant enrollment
Safety Issue:
Description:
Measure:Number of Participants With Anti-drug Antibody at any Visit
Time Frame:Approximately up to 4 years after first participant enrollment
Safety Issue:
Description:
Measure:Functional Assessment of Cancer Therapy -Leukemia (FACT-Leu) Score
Time Frame:Baseline to first follow-up after completion of study treatment, up to 4 years after first participant enrollment
Safety Issue:
Description:A 44-item, self-reported leukemia-specific measure that is used to quantitatively assess an individual's perception of how the disease affects their day-to-day life.
Measure:European Quality of Life- 5 Dimension 5-Level (EQ-5D-5L) Score
Time Frame:Baseline to first followup After completion of study treatment, up to 4 years after first participant enrollment
Safety Issue:
Description:A generic measure of health status with a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating of "health today".
Measure:Area under the concentration-time curve between time t1 and t2 (AUC t1-t2)
Time Frame:Prespecified time points during treatment through Cycle 1 (Days 1,2,3,4,8), cyc 2(Day 1), cyc 3,5 (Day 8) for part A and Cycle 1,4 (Days 1,5,8,9,22,23) cyc 2 (Days 1,8) for part B and also up to 30 days after last dose of any study drug in part A and B
Safety Issue:
Description:
Measure:Total Systemic Clearance (CL)
Time Frame:Prespecified time points during treatment through Cycle 1 (Days 1,2,3,4,8), cyc 2(Day 1), cyc 3,5 (Day 8) for part A and Cycle 1,4 (Days 1,5,8,9,22,23) cyc 2 (Days 1,8) for part B and also up to 30 days after last dose of any study drug in part A and B
Safety Issue:
Description:
Measure:Maximum Observed Serum Concentration (Cmax)
Time Frame:Prespecified time points during treatment through Cycle 1 (Days 1,2,3,4,8), cyc 2(Day 1), cyc 3,5 (Day 8) for part A and Cycle 1,4 (Days 1,5,8,9,22,23) cyc 2 (Days 1,8) for part B and also up to 30 days after last dose of any study drug in part A and B
Safety Issue:
Description:
Measure:Minimum Observed Concentration (Cmin)
Time Frame:Prespecified time points during treatment through Cycle 1 (Days 1,2,3,4,8), cyc 2(Day 1), cyc 3,5 (Day 8) for part A and Cycle 1,4 (Days 1,5,8,9,22,23) cyc 2 (Days 1,8) for part B and also up to 30 days after last dose of any study drug in part A and B
Safety Issue:
Description:
Measure:Volume of Distribution
Time Frame:Prespecified time points during treatment through Cycle 1 (Days 1,2,3,4,8), cyc 2(Day 1), cyc 3,5 (Day 8) for part A and Cycle 1,4 (Days 1,5,8,9,22,23) cyc 2 (Days 1,8) for part B and also up to 30 days after last dose of any study drug in part A and B
Safety Issue:
Description:
Measure:Time to Response
Time Frame:Disease assessment will continue until treatment failure or relapse or clinical cut-off (Approximately up to 4 years after first participant enrollment)
Safety Issue:
Description:Time to response will be defined as time from randomization to achieving response.
Measure:Duration of Response
Time Frame:Disease assessment will continue until treatment failure or relapse or clinical cut-off (Approximately up to 4 years after first participant enrollment)
Safety Issue:
Description:Duration of response will be defined as time from achieving response to relapse.
Measure:Percentage of Participants With Complete Response (CR) Along With Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi)
Time Frame:Disease assessment will continue until treatment failure or relapse or clinical cut-off (Approximately up to 4 years after first participant enrollment)
Safety Issue:
Description:CR is defined as 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 per liter (1000 per microliter); platelet count >100*10^9 per liter (100 000 per microliter); independence of red cell transfusions. CRi: All CR criteria except for residual neutropenia (<1.0*10^9 per liter [1000 per microliter) or thrombocytopenia (<100*10^9 per liter [100 000 per microliter). MRD negativity is defined as <1 blast or leukemic stem cell in 10,000 leukocytes (MRD level <10^4).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Janssen Research & Development, LLC

Trial Keywords

  • Leukemia, myeloid, acute
  • DACOGEN
  • Decitabine
  • JNJ-56022473
  • CLS362

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