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).
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Cusatuzumab | JNJ-74494550, ARGX-110 | Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA) |
| Azacitidine | Vidaza | Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA) |
| Venetoclax | Venclexta | Cohort 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
| Name | Type | Description | Interventions |
|---|
| Experimental: Cohort 2: Cusatuzumab + Venetoclax | Experimental | 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) | Experimental | 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). | - 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) 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 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: | 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: | 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: | Cohort 2 and 3: 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: | Cohort 2 and 3: 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: | Cohort 2 and 3: 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: | Active, not recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
May 21, 2021
