Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia
- Conditions
- Leukemia, Myeloid, Acute
- Interventions
- Registration Number
- NCT04150887
- Lead Sponsor
- OncoVerity, Inc.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 61
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental: Cohort 2: Cusatuzumab + Venetoclax Cusatuzumab 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. Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA) Azacitidine 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). Experimental: Cohort 2: Cusatuzumab + Venetoclax 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. Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA) Venetoclax 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). Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA) Cusatuzumab 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).
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
Serum Concentration of Cusatuzumab Up to 23 months Serum concentration of cusatuzumab will be assessed.
Number of Participants with Anti-cusatuzumab Antibodies Up to 23 months Number of participants with anti-drug antibodies to cusatuzumab will be reported.
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.
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.
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.
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.
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.
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).
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).
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.
Trial Locations
- Locations (23)
Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Kantonsspital St.Gallen
🇨ðŸ‡St. Gallen, Switzerland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
🇵🇱Lodz, Poland
Instytut Hematologii i Transfuzjologii
🇵🇱Warszawa, Poland
INSELSPITAL, Universitätsspital Bern
🇨ðŸ‡Bern, Switzerland
University of Rochester
🇺🇸Rochester, New York, United States
University of Toronto
🇨🇦Toronto, Ontario, Canada
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
City of Hope
🇺🇸Duarte, California, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Pittsburgh School of Medicine
🇺🇸Pittsburgh, Pennsylvania, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
Wisconsin Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Universitaetsklinik Hamburg-Eppendorf
🇩🇪Hamburg, Germany
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Klinikum der Universitaet Muenchen
🇩🇪München, Germany
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States