NCT04855136终止1 期
An Exploratory Phase 1/2 Trial to Determine Recommended Phase 2 Dose (RP2D), Safety and Preliminary Efficacy of bb2121 (Ide-cel) Combinations in Subjects With Relapsed/Refractory Multiple Myeloma (KarMMa-7)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 21
- 试验地点
- 34
- 主要终点
- Does Limiting Toxicity (DLT) rates _Phase 1
研究概览
简要总结
This is a global, open-label, multi-arm, multi-cohort, multi-center, phase 1/2 study to determine the safety, tolerability, efficacy, PK of bb2121 in combination with other therapies in adult subjects with R/RMM.
The following combinations will be
- Arm A will test bb2121 in combination with CC-220 (± low-dose dexamethasone)
- Arm B will test bb2121 in combination with BMS-986405 (JSMD194)
Combination agents being tested may be administered before, concurrently with and/or following (ie, maintenance) bb2121 infusion.
The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2). Dose expansion may occur in one or more arms.
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
- •Participants must satisfy the following criteria to be enrolled in the study:
- •Participant has documented diagnosis of MM and measurable disease, defined as:
- •M-protein (serum protein electrophoresis [sPEP ≥ 0.5 g/dL] or urine protein electrophoresis [uPEP]): uPEP ≥ 200 mg/24 hours and/or
- •Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
- •Participant has received:
- •at least 3 prior MM regimens for Arm A Cohort 1 and Arm B
- •at least 1 but no greater than 3 prior MM regimens for Arm A Cohort 2
- •Arm A Cohort 1 and Arm B: Participant has received prior treatment with an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody-containing regimen for at least 2 consecutive cycles.
- •Arm A Cohort 2: Participant has received prior treatment with an immunomodulatory agent for at least 2 consecutive cycles.
- •Evidence of PD during or within 6 months (measured from the last dose of any drug within the regimen) of completing treatment with the last antimyeloma regimen before study entry.
- •Participant achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •The presence of any of the following will exclude a participant from enrollment:
- •Participant has non-secretory MM or has history of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
- •Participant has any of the following laboratory abnormalities:
- •ANC and Platelets count as reported below
- •Hemoglobin < 8 g/dL (< 4.9 mmol/L) (transfusion is not permitted within 21 days of screening)
- •Creatinine clearance (CrCl) as reported below
- •Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
- •Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 ×upper limit of normal (ULN)
- •Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for participants with documented Gilbert's syndrome
- •International normalized ratio (INR) or activated partial thromboplastin time (aPTT) 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or participant requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors)
- •Participant has inadequate pulmonary function defined as oxygen saturation (SaO2) < 92% on room air.
- •Participant has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal.
- •Prior exposure to CC-220 (± low-dose dexamethasone) as part of their most recent antimyeloma treatment regimen (Arm A).
- •Prior exposure to BMS-986405 (JSMD194) (Arm B).
- •Previous history of an allogeneic hematopoietic stem cell transplantation, treatment with any gene therapy-based therapeutic for cancer, investigational cellular therapy for cancer or BCMA targeted therapy.
- •Treatment Arm A Cohort 1 and Arm B: participant has received autologous stem cell transplantation (ASCT) within 12 weeks prior to leukapheresis.
- •Treatment Arm A Cohort 2: participant has received autologous stem cell transplantation (ASCT) within 12 months prior to leukapheresis.
研究组 & 干预措施
Arm B- bb2121 in combination with BMS-986405 (JSMD194)
Experimental
- bb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agent will be administered during Month 1 starting from the day of bb2121 infusion
- Enrollment is closed for this Arm
干预措施: BMS-986405 (Drug)
Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)
Experimental
bb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules, depending on dose limiting toxicity (DLT) evaluation.
干预措施: BB2121 (Biological)
Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)
Experimental
bb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules, depending on dose limiting toxicity (DLT) evaluation.
干预措施: CC-220 (Drug)
Arm B- bb2121 in combination with BMS-986405 (JSMD194)
Experimental
- bb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agent will be administered during Month 1 starting from the day of bb2121 infusion
- Enrollment is closed for this Arm
干预措施: BB2121 (Biological)
结局指标
主要结局
Does Limiting Toxicity (DLT) rates _Phase 1
时间窗: Up to 28 days from start of the combination therapy
Percentage of participants experiencing DLTs
Complete Response Rate (CRR)_ Phase 2
时间窗: Up to 24 months
Proportion of participants who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by investigator's review
次要结局
- Incidence of Adverse Event (AEs)(Up to 24 months after the last participant received any study treatment)
- Overall Response Rate (ORR)(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Progression-free Survival (PFS)(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Overall Survival (OS)(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Time to response (TTR)(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Duration of Response (DoR)(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Time to next antimyeloma treatment (TTNT)(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Progression-free survival after next antimyeloma therapy (PFS2)(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Feasibility of maintenance therapy in combination with bb2121(Up to 4 months after bb2121 infusion in the respective cohort)
- Pharmacokinetics - Cmax_Phase 1 and 2(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Pharmacokinetics - Tmax_Phase 1 and 2(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Pharmacokinetics - AUC_Phase 1 and 2(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Pharmacokinetics - AUC0-28days _Phase 1 and 2(Up to 24 months after the last participant received any study treatment in the respective cohort)
- Pharmacokinetics - Tlast _Phase 1 and 2(Up to 24 months after the last participant received any study treatment in the respective cohort)
研究者
研究点 (34)
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