A Dose Escalation, Safety, Pharmacokinetic, Pharmacodynamic and Preliminary Efficacy Study of SAR650984 (Isatuximab) Administered Intravenously in Combination With Bortezomib - Based Regimens in Adult Patients With Newly Diagnosed Multiple Myeloma Non Eligible for Transplantation or No Intent for Immediate Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 90
- 试验地点
- 12
- 主要终点
- Overall response rate (VCDI)
研究概览
简要总结
Primary Objectives:
-
VCDI cohort:
-
To determine the maximum tolerated dose (MTD) and recommended dose (RD) of SAR650984 isatuximab when administered in combination with bortezomib (Velcade®) , cyclophosphamide, and dexamethasone (VCDI) based on the dose-limiting toxicity(ies) (DLTs) observed in patients with newly diagnosed multiple myeloma non-eligible for transplantation
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To evaluate safety and preliminary efficacy (overall response rate and complete response rate) of isatuximab administered at the selected dose in combination with bortezomib based regimin VCDI according to IMWG criteria.
-
VRDI Part A cohort and Part B cohort:
-
To evaluate the preliminary efficacy (complete response [CR] rate) of isatuximab administered at the selected dose in combination with bortezomib based regimen: VRDI, (bortezomib, lenalidomide, dexamethasone) according to IMWG criteria in adult patients with newly diagnosed MM non eligible for transplantation or no intent for immediate transplantation.
Secondary Objectives:
-
VCDI cohort:
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To characterize the overall safety profile of SAR650984 in combination with VCD regimen, including cumulative toxicities.
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To characterize the pharmacokinetic (PK) profile of SAR650984/isatuximab and each combination drug in VCDI regimen.
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To evaluate the immunogenicity of SAR650984 in combination treatments.
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To evaluate the preliminary efficacy of VCDI regimen in terms of duration of response and progression-free survival.
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To assess the relationship between clinical effects (adverse event [AE] and/or tumor response) and CD38 receptor density.
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VRDI Part A cohort and Part B cohort:
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To characterize the overall safety profile of isatuximab in combination with VRD regimen.
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To evaluate the infusion duration (only applicable for VRDI Part B cohort)
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To characterize the PK profile of isatuximab and each combination drug in VRDI regimen.
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To evaluate the immunogenicity of isatuximab in combination treatments.
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To evaluate the preliminary efficacy of VRDI regimen in terms of ORR, DOR, and PFS.
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To evaluate the impact of M protein measurement without isatuximab interference (via the SEBIA HYDRASHIFT 2/4 isatuximab IFE test) on CR and BOR assessment.
-
To assess the relationship between clinical effects (AE and/or tumor response) and CD38 receptor density (only applicable for VRDI Part A cohort).
-
To assess MRD negativity rate in patients achieving a CR or VGPR and explore correlation with clinical outcome.
详细描述
The duration of the study for an individual patient will include:
- A period to assess eligibility (screening or baseline period) of up to 3 weeks for VCDI cohort, up to 28 days for VRDI cohort;
- for patients in the VCDI cohort: a treatment period including up to 12 induction treatment cycles (50-week duration).
- for patients in the VRDI cohort: a treatment period including up to 4 induction cycles (24 week duration).
- Following induction, both cohorts have maintenance periods consisting of 4 week cycles until progression, unacceptable AE, or patient willingness to discontinue and an end-of-treatment visit at least 30 days following the last administration of treatment.
- Patients that discontinue therapy for reasons other than progression will have follow-up visits until progression or until the patient receives another anticancer therapy, whichever is earlier.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Isatuximab
VCDI cohort: Isatuximab (escalating dose) + bortezomib + cyclophosphamide + dexamethasone (VCDI): Induction phase will be 50 weeks (12 cycles). The duration of a cycle will be 42 days (6 weeks) for Cycle 1 (C1) and 28 days (4 weeks) for subsequent cycles. The duration of a cycle of the maintenance phase will be 28 days (4 weeks). After C12, isatuximab will be administered at its initial assigned dose and dexamethasone once every 28 days.
VRDI cohort parts A and B: Isatuximab + bortezomib + dexamethasone + lenalidomide (VRDI): Induction phase will be 24 weeks (4 cycles at 6 weeks/cycle). The duration of a cycle of the maintenance phase will be 28 days (4 weeks). Maintenance therapy may continue until disease progression, unacceptable AE or patient willingness to discontinue.
VRDI Part A: Enrollment to begin after the VCDI cohort is completed.
VRDI Part B: Enrollment to begin after the VRDI part A is completed.
干预措施: lenalidomide (Drug)
Isatuximab
VCDI cohort: Isatuximab (escalating dose) + bortezomib + cyclophosphamide + dexamethasone (VCDI): Induction phase will be 50 weeks (12 cycles). The duration of a cycle will be 42 days (6 weeks) for Cycle 1 (C1) and 28 days (4 weeks) for subsequent cycles. The duration of a cycle of the maintenance phase will be 28 days (4 weeks). After C12, isatuximab will be administered at its initial assigned dose and dexamethasone once every 28 days.
VRDI cohort parts A and B: Isatuximab + bortezomib + dexamethasone + lenalidomide (VRDI): Induction phase will be 24 weeks (4 cycles at 6 weeks/cycle). The duration of a cycle of the maintenance phase will be 28 days (4 weeks). Maintenance therapy may continue until disease progression, unacceptable AE or patient willingness to discontinue.
VRDI Part A: Enrollment to begin after the VCDI cohort is completed.
VRDI Part B: Enrollment to begin after the VRDI part A is completed.
干预措施: bortezomib (Drug)
Isatuximab
VCDI cohort: Isatuximab (escalating dose) + bortezomib + cyclophosphamide + dexamethasone (VCDI): Induction phase will be 50 weeks (12 cycles). The duration of a cycle will be 42 days (6 weeks) for Cycle 1 (C1) and 28 days (4 weeks) for subsequent cycles. The duration of a cycle of the maintenance phase will be 28 days (4 weeks). After C12, isatuximab will be administered at its initial assigned dose and dexamethasone once every 28 days.
VRDI cohort parts A and B: Isatuximab + bortezomib + dexamethasone + lenalidomide (VRDI): Induction phase will be 24 weeks (4 cycles at 6 weeks/cycle). The duration of a cycle of the maintenance phase will be 28 days (4 weeks). Maintenance therapy may continue until disease progression, unacceptable AE or patient willingness to discontinue.
VRDI Part A: Enrollment to begin after the VCDI cohort is completed.
VRDI Part B: Enrollment to begin after the VRDI part A is completed.
干预措施: cyclophosphamide (Drug)
Isatuximab
VCDI cohort: Isatuximab (escalating dose) + bortezomib + cyclophosphamide + dexamethasone (VCDI): Induction phase will be 50 weeks (12 cycles). The duration of a cycle will be 42 days (6 weeks) for Cycle 1 (C1) and 28 days (4 weeks) for subsequent cycles. The duration of a cycle of the maintenance phase will be 28 days (4 weeks). After C12, isatuximab will be administered at its initial assigned dose and dexamethasone once every 28 days.
VRDI cohort parts A and B: Isatuximab + bortezomib + dexamethasone + lenalidomide (VRDI): Induction phase will be 24 weeks (4 cycles at 6 weeks/cycle). The duration of a cycle of the maintenance phase will be 28 days (4 weeks). Maintenance therapy may continue until disease progression, unacceptable AE or patient willingness to discontinue.
VRDI Part A: Enrollment to begin after the VCDI cohort is completed.
VRDI Part B: Enrollment to begin after the VRDI part A is completed.
干预措施: dexamethasone (Drug)
Isatuximab
VCDI cohort: Isatuximab (escalating dose) + bortezomib + cyclophosphamide + dexamethasone (VCDI): Induction phase will be 50 weeks (12 cycles). The duration of a cycle will be 42 days (6 weeks) for Cycle 1 (C1) and 28 days (4 weeks) for subsequent cycles. The duration of a cycle of the maintenance phase will be 28 days (4 weeks). After C12, isatuximab will be administered at its initial assigned dose and dexamethasone once every 28 days.
VRDI cohort parts A and B: Isatuximab + bortezomib + dexamethasone + lenalidomide (VRDI): Induction phase will be 24 weeks (4 cycles at 6 weeks/cycle). The duration of a cycle of the maintenance phase will be 28 days (4 weeks). Maintenance therapy may continue until disease progression, unacceptable AE or patient willingness to discontinue.
VRDI Part A: Enrollment to begin after the VCDI cohort is completed.
VRDI Part B: Enrollment to begin after the VRDI part A is completed.
干预措施: isatuximab SAR650984 (Drug)
结局指标
主要结局
Overall response rate (VCDI)
时间窗: Up to 34 weeks of treatment (induction phase)
Assessment of dose-limiting toxicities (DLTs) in VCDI cohort
时间窗: Up to 6 weeks per treated patient
Complete response rate (VCDI)
时间窗: Up to 34 weeks of treatment (induction phase)
Complete response rate (VRDI)
时间窗: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts
次要结局
- Overall response rate (VRDI)(Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts)
- Infusion duration(VRDI Part B: Up to 104 weeks of treatment)
- Progression-free survival for VCDI(VCDI: 30 months after LPI)
- MRD negativity rate(Up to 3 years of treatment (induction and maintenance phase) in VRDI part A and part B cohorts)
- Number of patients with adverse events (AEs), clinically significant changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling(VCDI: Up to approximately 106 weeks, VRDI Part A and Part B: Up to approximately 104 weeks)
- Assessment of PK parameter: Partial area under the serum concentration time curve (AUC)(VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks)
- Levels of human antidrug antibodies (ADA)(VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks)
- Duration of response - time(VCDI and VRDI: Until treatment discontinuation by the last patient)
- Progression-free survival for VRDI(VRDI Part A and Part B: 24 months after LPI)
- Assessment of PK parameter: Maximum observed concentration (Cmax)(VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks)