A Phase 1/2, Open-label Randomized Study of Ulocuplumab (BMS-936564) in Combination With Low Dose Cytarabine in Subjects With Newly Diagnosed Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 70
- 试验地点
- 16
- 主要终点
- Number of Participants With >= Grade 3 AEs - Phase 1
研究概览
简要总结
The purpose of this study is to determine the safety and effectiveness of ulocuplumab in combination with low dose cytarabine in the treatment of Newly Diagnosed Acute Myeloid Leukemia (AML).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Newly Diagnosed Acute Myeloid Leukemia (AML)
- •Considered inappropriate for intensive remission induction therapy by an investigator
- •Not eligible for stem cell transplantation
排除标准
- •Acute promyelocytic leukemia
- •Current Myelodysplastic syndrome only subjects
- •Unstable angina or uncontrolled congestive heart failure
- •Any other malignancy, excluding basal or squamous cell carcinoma of the skin, in situ melanoma, cervical carcinoma in situ, localized prostate cancer, or superficial bladder cancer stage 0, from which the subject has not been disease-free for at least 3 years
- •Respiratory disease requiring continuous supplemental oxygen
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
low dose Cytarabine only
Low Dose Cytarabine only Phase 2 (expansion cohort)
干预措施: BMS-936564 (Drug)
Ulocuplumab + low dose Cytarabine
Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment
干预措施: BMS-936564 (Drug)
Ulocuplumab + low dose Cytarabine
Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment
干预措施: Cytarabine (Drug)
Ulocuplumab Dose A + low dose Cytarabine
Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)
干预措施: BMS-936564 (Drug)
low dose Cytarabine only
Low Dose Cytarabine only Phase 2 (expansion cohort)
干预措施: Cytarabine (Drug)
Ulocuplumab Dose A + low dose Cytarabine
Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)
干预措施: Cytarabine (Drug)
Ulocuplumab Dose B + low dose Cytarabine
Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)
干预措施: BMS-936564 (Drug)
Ulocuplumab Dose B + low dose Cytarabine
Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)
干预措施: Cytarabine (Drug)
结局指标
主要结局
Number of Participants With >= Grade 3 AEs - Phase 1
时间窗: From first dose to 30 days post last dose
The number of participants with an on-study adverse event \>= Grade level 3. Safety data are evaluated for \>= Grade 3 AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Number of Participants With Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1 - Phase 1
时间窗: From first dose to end of cycle 1 (28 days)
Safety data evaluated for DLTs. DLTs and all other toxicities were defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). DLTs were defined based upon events that were considered to be related to ulocuplumab in combination with LDAC and that occurred during the first cycle of drug administration (28 days).
Number of Participants With Adverse Events (AEs) - Phase 1
时间窗: From first dose to 30 days post last dose
The number of participants with an on-study adverse event (AE). Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Number of Deaths - Phase 1
时间窗: From first dose to 30 days post last dose
The number of participants who died.
Number of Participants With AEs Leading to Discontinuation - Phase 1
时间窗: From first dose to 30 days post last dose
The number of participants with an on-study adverse event (AE) leading to discontinuation. Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Number of Participants With Serious Adverse Events (SAEs) - Phase 1
时间窗: From first dose to 30 days post last dose
The number of participants with an on-study serious adverse event (SAE). Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Number of Participants With Laboratory Abnormalities - Phase 1
时间窗: From first dose to 30 days post last dose
The number of participants with an on-study laboratory abnormality. Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). grades 1, 2, 3, 4, 5, unknown, with 5 being the worst outcome
Best Overall Response (BOR) - Phase 2
时间窗: From first dose until a minimum follow-up of up to 2 months
The phase 2 primary endpoint was based on the rate of Complete Remission (CR/CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 primary analysis was conducted after all participants had an opportunity for 6 months of follow-up. Complete remission rate: CR + CRi, confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count
次要结局
- Number of Deaths- Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2(Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up))
- Best Overall Response (BOR) - Phase 1(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With AEs - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With AEs Leading to Discontinuation - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With SAEs - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With Laboratory Abnormalities - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2(From first dose until a minimum follow-up of up to 2 months)
- Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2(Cycle 1 Day 1)
- Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2(Cycle 1 Day 1)
- Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2(Cycle 1 Day 1)
- Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2(Cycle 1 Day 1)
- Area Under the Ulocuplumab Concentration-time Curve From Time Zero to Infinity [AUC(INF)] - Phases 1 and 2(Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up))
- Elimination Half-life (T-HALF) - Phases 1 and 2(Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up))
- Volume of Distribution at Steady State (Vss) - Phases 1 and 2(Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up))
- Overall Rate of Remission in Participants Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2(From first dose until a minimum follow-up of up to 2 months)
- Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2(From first dose until a minimum follow-up of up to 2 months)
- Total Body Clearance of Ulocuplumab (CLT) - Phases 1 and 2(Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up))
- Duration of Response in Participants With CR/CRi Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Participants Treated With LDAC Only - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2(From first dose until a minimum follow-up of up to 2 months)
- Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2(From first dose until a minimum follow-up of up to 2 months)
- Overall Survival (OS) - Phases 1 and 2(From first dose until a minimum follow-up of up to 2 months)
- Duration of Response in Participants With CR/CRi Treated With LDAC Only - Phase 2(From first dose until a minimum follow-up of up to 2 months)