An Open-label, Multicenter, Phase 1b Study of OV-1001 (Cusatuzumab; Anti-CD70 Monoclonal Antibody) in Combination With Background Therapy for the Treatment of Subjects With Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 61
- 试验地点
- 44
- 主要终点
- Frequency and Severity of Adverse Events (AEs), Laboratory Abnormalities, and Physical Exam Findings as a Measure of Safety
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: Cusatuzumab (Drug)
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.
干预措施: Venetoclax (Drug)
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).
干预措施: Cusatuzumab (Drug)
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).
干预措施: Azacitidine (Drug)
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).
干预措施: Venetoclax (Drug)
结局指标
主要结局
Frequency and Severity of Adverse Events (AEs), Laboratory Abnormalities, and Physical Exam Findings as a Measure of Safety
时间窗: Up to 42 months
Frequency and severity of AEs, laboratory abnormalities, and physical exam findings will be reported.
次要结局
- Percentage of Participants with Complete Remission with Partial Hematological Recovery (CRh)(Up to 42 months)
- Percentage of Participants with CR plus CRh(Up to 42 months)
- Serum Concentration of Cusatuzumab(Up to 23 months)
- Number of Participants with Anti-cusatuzumab Antibodies(Up to 23 months)
- Percentage of Participants with Complete Response (CR)(Up to 42 months)
- Percentage of Participants with CR with Incomplete Recovery (CRi)(Up to 42 months)
- Overall Response Rate (ORR)(Up to 42 months)
- Cohort 2 and 3: Time to Response(Up to 42 months)
- Cohort 2 and 3: Duration of Response(Up to 42 months)
- Percentage of Participants with CR without MRD(Up to 42 months)
- Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)(Up to 42 months)
- Cohort 2 and 3: Red Blood Cell (RBC) or Platelet Transfusion Independence(Up to 42 months)