NCT01120457已完成1 期
A Phase 1, Open-label, Multicenter Study of BMS-936564 (MDX-1338) in Subjects With Relapsed Acute Myelogenous Leukemia and Selected B-cell Malignancies
Bristol-Myers Squibb11 个研究点 分布在 1 个国家目标入组 96 人开始时间: 2010年8月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 96
- 试验地点
- 11
- 主要终点
- Safety and tolerability as monotherapy
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of BMS-936564 (MDX-1338) in relapsed Acute myelogenous leukemia (AML) and other selected B-cell cancers and to determine the maximum tolerated dose (MTD) of the drug alone in relapsed/refractory 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
- •A. Common to All Indications:
- •Life expectancy at least 12 weeks
- •ECOG Performance Status of 0-2
- •B. For Acute myelogenous leukemia (AML) Subjects:
- •First Relapse and primary induction failure in AML (M3 excluded)
- •Secondary AML subjects from myelodysplastic syndrome (MDS) or prior chemotherapy are eligible. MDS-only subjects are not eligible
- •C. For Follicular Lymphoma (FL), Diffuse Large B-Cell Lymphoma (DLBCL) Subjects:
- •Must be at least 4 weeks (for FL) or 2 weeks (for DLBCL) since prior cytotoxic, biologic, monoclonal antibody, or investigational therapy
- •Ability to undergo tumor biopsy pre-treatment and at end of monotherapy period (though not mandatory for all subjects)
- •Subjects must have a histologically confirmed diagnosis of relapsed or refractory disease
- •D. For Chronic lymphocytic leukemia (CLL) Subjects:
- •Subjects must have a histologically confirmed diagnosis of relapsed or refractory disease
- •Must be at least 4 weeks since prior cytotoxic, biologic, monoclonal antibody, or investigational therapy, including corticosteroids
排除标准
- •A. Common to All indications:
- •Prior anti-CXCR4 therapy including BMS-936564 (MDX-1338)
- •Less than 3 months from prior hematopoietic stem cell transplant
- •Presence of active graft versus host disease
- •B. For AML Subjects:
- •Acute promyelocytic leukemia (M3)
- •Left ventricular ejection fraction < institutional limits of normal
- •C. For FL, DLBCL Subjects:
- •(For DLBCL): Inadequate renal function defined as creatinine clearance (by Cockcroft-Gault formula) < 60 mL/min
- •Major surgery, not related to debulking procedures, within 21 days of first dose
- •Myocardial infarction within 6 months prior to screening or Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
- •Myelodysplastic syndrome (MDS)
- •D. For CLL Subjects:
- •No progression to more aggressive B-cell cancers, such as Richter's syndrome
- •Major surgery within 21 days of Cycle 1, Day
- •Patients undergoing debulking procedures and minor surgery are allowed after a recovery period, in the judgment of the Investigator
- •Myocardial infarction within 6 months prior to screening Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
研究组 & 干预措施
Arm 1: Dose Escalation and Expansion cohort (AML Patients)
Experimental
Dose Escalation: BMS-936564 0.3-10 mg/kg solution, Intravenous, Single 60 minute infusion as monotherapy 7 days/cycle 1 and with chemotherapy for subsequent cycles (28 days/cycle)
Dose Expansion: BMS-936564 maximum tolerated dose (MTD) based on dose escalation, solution, Intravenous, Single 60 minute infusion as monotherapy 7 days/cycle 1 and with chemotherapy for subsequent cycles (28 days/cycle)
干预措施: BMS-936564 (Anti-CXCR4) (Drug)
Arm 2: Dose Expansion cohort (DLBCL Patient)
Experimental
BMS-936564 MTD based on Arm 1, weekly 60 minute infusion in cycle 1 (up to 56 days) and with chemotherapy for subsequent cycles (28 days/cycle)
干预措施: BMS-936564 (Anti-CXCR4) (Drug)
Arm 3: Dose Expansion cohort (CLL Patient)
Experimental
BMS-936564 MTD based on Arm 1, weekly 60 minute infusion in cycle 1 (up to 56 days) and with chemotherapy for subsequent cycles (28 days/cycle)
干预措施: BMS-936564 (Anti-CXCR4) (Drug)
Arm 4: Dose Expansion cohort (FL Patient)
Experimental
BMS-936564 MTD based on Arm 1, weekly 60 minute infusion in cycle 1 (up to 56 days) and with chemotherapy for subsequent cycles (28 days/cycle)
干预措施: BMS-936564 (Anti-CXCR4) (Drug)
结局指标
主要结局
Safety and tolerability as monotherapy
时间窗: Within 28 days for the selected B-cell malignancies
Safety and tolerability measured by incidence of adverse events (AEs), AEs leading to discontinuation, Serious Adverse Events (SAEs), deaths, and laboratory abnormalities
次要结局
- Trough observed serum concentration (Cmin) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Safety, as measured by vital signs, clinical laboratory tests,ECOG performance status, physical exams, 12 lead ECGs incidence and severity of adverse events(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Efficacy- including best overall response (BOR) derived from changes in tumor burden and metabolic response based on FDG-PET (for DLBCL)(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Maximum observed serum concentration (Cmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Time of maximum observed concentration (Tmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Biomarker- characterizing the pharmacodynamic (PD) profiles of BMS-936564 (MDX-1338). The main PD biomarkers are cell trafficking(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Half life (T-HALF) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Immunogenicity measurement for human anti human antibodies (HAHA) -characterizing the immunogenicity of BMS-936564(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Exploratory Biomarkers- are detection of apoptosis, cytokine analyses, CXCR4 expression, ZAP-70 and CD38 expression(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Total body clearance(CLT) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
- Volume of distribution at steady-state (Vss) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time(For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies)
研究者
研究点 (11)
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