Clinical Trials /

Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia

NCT04150887

Description:

The purpose of the study is to characterize safety and tolerability of cusatuzumab in combination with various therapies used to treat acute myeloid leukemia (AML).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia
  • Official Title: An Open-label, Multicenter, Phase 1b Study of JNJ-74494550 (Cusatuzumab; Anti-CD70 Monoclonal Antibody) in Combination With Background Therapy for the Treatment of Subjects With Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: CR108710
  • SECONDARY ID: 2019-002808-41
  • SECONDARY ID: 74494550AML1003
  • NCT ID: NCT04150887

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
CusatuzumabJNJ-74494550, ARGX-110Cohort 1: Cusatuzumab + Azacitidine (CA)
AzacitidineVidazaCohort 1: Cusatuzumab + Azacitidine (CA)
VenetoclaxVenclextaCohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA)

Purpose

The purpose of the study is to characterize safety and tolerability of cusatuzumab in combination with various therapies used to treat acute myeloid leukemia (AML).

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: Cusatuzumab + Azacitidine (CA)ExperimentalParticipants will receive cusatuzumab 20 milligram per kilogram (mg/kg) intravenously (IV) in combination with azacitidine 75 milligram per meter square (mg/m^2) subcutaneously (SC) or IV (as background therapy).
  • Cusatuzumab
  • Azacitidine
Experimental: Cohort 2: Cusatuzumab + Venetoclax (CV)ExperimentalParticipants enrolled in this cohort (applicable only for US sites) will receive cusatuzumab 20 mg/kg IV in combination with venetoclax ramp-up to 400 mg orally (as background therapy).
  • Cusatuzumab
  • Venetoclax
Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA)ExperimentalParticipants enrolled at US sites will receive cusatuzumab 10 mg/kg and potentially escalate to 20 mg/kg IV in combination with azacitidine 75 mg/m^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies). Participants enrolled from ex-US sites will receive cusatuzumab 20 mg/kg and potentially de-escalate to 10 mg/kg IV in combination with azacitidine 75 mg/m^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies).
  • Cusatuzumab
  • Azacitidine
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of acute myeloid leukemia (AML) according to World Health Organization 2016
             criteria . Participants with acute promyelocytic leukemia (APL) with t (15;17) or its
             molecular equivalent (promyelocytic leukemia/retinoic acid receptor alpha [PML RAR
             alpha]) are not eligible

          -  Must be ineligible for intensive chemotherapy

          -  De novo or secondary AML

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Previously untreated AML except: emergency leukapheresis, hydroxyurea, and/or 1 dose
             1-2 gram per meter square (g/m^2) cytarabine during the Screening Phase to control
             hyperleukocytosis. These treatments must be discontinued greater than or equal to (>=)
             24 hours prior to start of study drug. Empiric all trans retinoic acid (ATRA)
             treatment for presumed acute promyelocytic leukemia (APL) is permitted but APL must be
             ruled out and ATRA must be discontinued >=24 hours prior to the start of study drug

          -  Contraceptive use by men or women should be consistent with local regulations
             regarding the use of contraceptive methods for participants participating in clinical
             studies

        Exclusion Criteria:

          -  Leukemic involvement of the central nervous system

          -  Eligible for an allogeneic hematopoietic stem cell transplantation at study entry

          -  Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug

          -  A history of human immunodeficiency virus (HIV) antibody positive or tests positive
             for HIV if tested at screening

          -  Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax,
             azacitidine, or their excipients (example: mannitol, an excipient of azacitidine)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency and Severity of Adverse Events (AEs), Laboratory Abnormalities, and Physical Exam Findings as a Measure of Safety
Time Frame:Up to 32 months
Safety Issue:
Description:Frequency and severity of AEs, laboratory abnormalities, and physical exam findings will be reported.

Secondary Outcome Measures

Measure:Serum Concentration of Cusatuzumab
Time Frame:Up to 32 months
Safety Issue:
Description:Serum concentration of cusatuzumab will be assessed.
Measure:Number of Participants with Anti-cusatuzumab Antibodies
Time Frame:Up to 32 months
Safety Issue:
Description:Number of participants with anti-drug antibodies to cusatuzumab will be reported.
Measure:Percentage of Participants with Complete Response (CR)
Time Frame:Up to 32 months
Safety Issue:
Description:Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.
Measure:Percentage of Participants with Complete Remission with Partial Hematological Recovery (CRh)
Time Frame:Up to 32 months
Safety Issue:
Description:Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.
Measure:Percentage of Participants with CR plus CRh
Time Frame:Up to 32 months
Safety Issue:
Description:Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.
Measure:Percentage of Participants with CR with Incomplete Recovery (CRi)
Time Frame:Up to 32 months
Safety Issue:
Description:Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 32 months
Safety Issue:
Description:ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.
Measure:Percentage of Participants with CR without MRD
Time Frame:Up to 32 months
Safety Issue:
Description:Percentage of participants with CR without minimal residual disease (MRD) will be reported and is defined as less than (<) 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3).
Measure:Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)
Time Frame:Up to 32 months
Safety Issue:
Description:Percentage of participants with negative MRD who achieved CR, CRh, CRi, or MLFS will be reported and is defined as < 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3).
Measure:Time to Response
Time Frame:Up to 32 months
Safety Issue:
Description:Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi.
Measure:Duration of Response
Time Frame:Up to 32 months
Safety Issue:
Description:Duration of response is defined as time from achieving the first response of CR, CRh, or CRi to hematologic relapse or death of any cause.
Measure:Red Blood Cell (RBC) or Platelet Transfusion Independence
Time Frame:Up to 32 months
Safety Issue:
Description:Transfusion independence (RBC or platelets) is defined as a period of greater than or equal to (>=) 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug +30 days.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

December 23, 2019