A Phase 1b Study of SAR650984 (Anti-CD38 mAb) in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 57
- 试验地点
- 5
- 主要终点
- Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD
研究概览
简要总结
Primary Objectives:
- To determine the maximum tolerated dose of SAR650984 (isatuximab) with lenalidomide and dexamethasone (LD) in patients with relapsed or refractory multiple myeloma.
- Expansion Phase Only: To further evaluate preliminary evidence of antitumor activity (objective response rate [ORR]) of SAR650984 (isatuximab) in combination with LD using International Myeloma Working Group (IMWG) criteria.
Secondary Objectives:
- To evaluate the safety, including immunogenicity, of SAR650984 (isatuximab) in combination with LD in relapsed or refractory multiple myeloma. The severity, frequency and incidence of all toxicities will be assessed.
- To evaluate the pharmacokinetics (PK) of SAR650984 (isatuximab) when administered in combination with LD and the PK of lenalidomide in combination with SAR650984 and dexamethasone.
- To assess the relationship between clinical (adverse event [AE] and/or tumor response) effects and pharmacologic parameters (PK/pharmacodynamics), and/or biologic (correlative laboratory) results.
- For the dose expansion phase, estimate the activity (ORR) using IMWG defined response criteria of SAR650984 (isatuximab) plus LD.
- To describe progression-free survival (PFS) in patients treated with this combination.
详细描述
The study duration for an individual patient will include a screening period for inclusion of up to 21 days, and at least 4 weeks of treatment in the absence of severe adverse reaction, dose limiting toxicity or disease progression plus up to 60 days post-treatment follow up. The treatment period may continue until disease progression, intolerable toxicity, or Investigator, sponsor, or patient decision to discontinue therapy. After study treatment discontinuation, an end of treatment (EOT) visit will be done at 30 days to assess safety, and at 30 and 60 days for anti-drug antibody (ADA) and PK. If the ADA is positive or inconclusive at day 60, then PK and ADA will be repeated every 30 days until ADA is negative. Patients who discontinue treatment for reasons other than progression of disease will be followed monthly until progression, initiation of subsequent therapy, or until the primary analysis cutoff date, whichever comes first.
研究设计
- 研究类型
- Interventional
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SAR650984 (isatuximab)
SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression.
For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle.
干预措施: isatuximab SAR650984 (Drug)
SAR650984 (isatuximab)
SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression.
For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle.
干预措施: lenalidomide (Drug)
SAR650984 (isatuximab)
SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression.
For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle.
干预措施: dexamethasone (Drug)
结局指标
主要结局
Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD
时间窗: Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment
次要结局
- Assessment of PK parameters - maximum concentration (Cmax)(Up to disease progression plus 60 days)
- Assessment of PK parameters - concentration observed at end of infusion (Ceoi)(Up to disease progression plus 60 days)
- CD38 receptor density(Up to disease progression plus 60 days)
- Preliminary assessment of progression-free survival (PFS)(Up to disease progression)
- Preliminary assessment of overall response rate(9 months from the last investigational medicinal product (IMP)/non-IMP (NIMP) administration)
- Assessment of PK parameters - plasma concentration observed just before treatment administration during repeated dosing (Ctrough)(Up to disease progression plus 60 days)
- Number of CD38 receptors occupied by SAR650984 (isatuximab)(Up to disease progression plus 60 days)
- Assessment of PK parameters - time to reach Cmax (Tmax)(Up to disease progression plus 60 days)
- Assessment of PK parameters - area under the plasma concentration versus time curve over the dosing interval (AUCtau)(Up to disease progression plus 60 days)
- Immunogenicity: Number of anti-SAR650984 (isatuximab) antibodies in response to SAR650984 (isatuximab)(Up to disease progression plus 60 days)