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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04150887
Collaborator
argenx (Industry)
61
Enrollment
23
Locations
2
Arms
42.2
Anticipated Duration (Months)
2.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
61 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 23, 2019
Anticipated Primary Completion Date :
Dec 30, 2022
Anticipated Study Completion Date :
Jun 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Experimental: Cohort 2: Cusatuzumab + Venetoclax

Participants enrolled in this cohort will receive venetoclax ramp-up to 400 mg orally (as background therapy) starting on Cycle 1 Day 1 and followed by 400 mg daily dosing starting on Cycle 1 Day 4 plus cusatuzumab IV on Day 3 and Day 17 of each 28-day cycle. Cohort 2 will not be enrolled in the US.

Drug: Cusatuzumab
Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.
Other Names:
  • JNJ-74494550
  • ARGX-110

    • Drug: Venetoclax
    Venetoclax will be administered orally and the dose will ramp-up to 400 mg.
    Other Names:
  • Venclexta

    		•
    Experimental: Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA)

    Participants 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).

    Drug: Cusatuzumab
    Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.
    Other Names:
  • JNJ-74494550
  • ARGX-110

    • Drug: Azacitidine
    Azacitidine will be administered 75 mg/m^2 subcutaneously or intravenously.
    Other Names:
  • Vidaza

    • Drug: Venetoclax
    Venetoclax will be administered orally and the dose will ramp-up to 400 mg.
    Other Names:
  • Venclexta

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Frequency and Severity of Adverse Events (AEs), Laboratory Abnormalities, and Physical Exam Findings as a Measure of Safety [Up to 42 months]

      Frequency and severity of AEs, laboratory abnormalities, and physical exam findings will be reported.

    Secondary Outcome Measures

    1. Serum Concentration of Cusatuzumab [Up to 23 months]

      Serum concentration of cusatuzumab will be assessed.

    2. Number of Participants with Anti-cusatuzumab Antibodies [Up to 23 months]

      Number of participants with anti-drug antibodies to cusatuzumab will be reported.

    3. Percentage of Participants with Complete Response (CR) [Up to 42 months]

      Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.

    4. Percentage of Participants with Complete Remission with Partial Hematological Recovery (CRh) [Up to 42 months]

      Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.

    5. Percentage of Participants with CR with Incomplete Recovery (CRi) [Up to 42 months]

      Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.

    6. Percentage of Participants with CR plus CRh [Up to 42 months]

      Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.

    7. Overall Response Rate (ORR) [Up to 42 months]

      ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.

    8. Percentage of Participants with CR without MRD [Up to 42 months]

      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).

    9. Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS) [Up to 42 months]

      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).

    10. Cohort 2 and 3: Time to Response [Up to 42 months]

      Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi.

    11. Cohort 2 and 3: Duration of Response [Up to 42 months]

      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.

    12. Cohort 2 and 3: Red Blood Cell (RBC) or Platelet Transfusion Independence [Up to 42 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Diagnosis of acute myeloid leukemia (AML) according to World Health Organization 2016 criteria . Participants with acute promyelocytic leukemia (APL) 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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Duarte California United States 91010-3000
    2 Norton Cancer Institute Louisville Kentucky United States 40207
    3 Barbara Ann Karmanos Cancer Institute Detroit Michigan United States 48201
    4 Roswell Park Cancer Institute Buffalo New York United States 14203
    5 Weill Cornell Medicine New York New York United States 10021
    6 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    7 University of Rochester Rochester New York United States 14642
    8 University of Pittsburgh School of Medicine Pittsburgh Pennsylvania United States 15232
    9 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    10 University of Vermont Burlington Vermont United States 05401
    11 Wisconsin Medical Center Milwaukee Wisconsin United States 53226
    12 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    13 University of Alberta Hospital Edmonton Alberta Canada T6G 2B7
    14 University of Toronto Toronto Ontario Canada M5G 2M9
    15 McGill University Health Centre Montreal Quebec Canada H4A 3J1
    16 Universitaetsklinik Hamburg-Eppendorf Hamburg Germany 20246
    17 Universitatsklinikum Leipzig Leipzig Germany 04103
    18 Klinikum der Universität München München Germany 81377
    19 Szpital Uniwersytecki w Krakowie Krakow Poland 31-501
    20 Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi Lodz Poland 93-513
    21 Instytut Hematologii i Transfuzjologii Warszawa Poland 02-776
    22 INSELSPITAL, Universitätsspital Bern Bern Switzerland 3010
    23 Kantonsspital St.Gallen St. Gallen Switzerland 9007

    Sponsors and Collaborators

    • Janssen Research & Development, LLC
    • argenx

    Investigators

    • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT04150887
    Other Study ID Numbers:
    • CR108710
    • 2019-002808-41
    • 74494550AML1003
    First Posted:
    Nov 5, 2019
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Azacitidine
    Venetoclax

    Study Results

    No Results Posted as of Aug 12, 2022