Study of AVE1642 Anti-IGF1R Monoclonal Antibody in Patients With Advanced Multiple Myeloma
2010年11月2日 更新者：Sanofi
Open Label Study of the Anti Insulin-like Growth Factor 1 Receptor (IGF-1R) Monoclonal Antibody, AVE1642, as Single Agent (Dose Escalation, Part 1) and in Combination With Velcade® (Combination, Part 2) in Patients With Recurrent, Refractory Multiple Myeloma (MM)
Primary Objectives:
Study Part 1: Determine the selected dose of AVE1642 administered every 3 weeks based on pharmacokinetic (PK) (Clearance of AVE1642), pharmacodynamic (PD) (insulin-like growth factor 1 [IGF-1] serum level) parameters, and eventual dose limiting toxicities (DLTs) in patients with recurrent, refractory multiple myeloma (MM).
Study Part 2: Assess the safety of the combination of the selected dose of AVE1642 with the recommended dose of Velcade®.
Secondary Objectives :
Study Part 1:
- To assess the safety profile: type, incidence and intensity of drug related adverse events (AEs)
- To assess the biological activity of AVE1642 (saturation of the receptors and down-regulation) on malignant plasma cells and on peripheral blood mononuclear cells (PBMC) and granulocytes
- To assess the biological activity of AVE1642 on the signalization pathway of the IGF-1 system (phosphorylated akt [pAkt], phosphorylated erk [pErk]) on malignant plasma cells when technically possible
- To define PK profile of AVE1642, and its PD effects on serum IGF 1, GF 2 and IGFBP-3
- To assess clinical efficacy (complete response [CR], partial response [PR], minimal response [MR] and stabilization) based on the European group for Blood and Marrow Transplantation (EBMT) criteria, when possible
- To assess potential immunogenicity by detection of human antihumanized antibodies (HAHA) anti-AVE1642
Study Part 2:
- To detect any PK or PD interaction between AVE1642 and Velcade®
- To assess clinical efficacy (CR, PR, MR, no change [NC]) according to EBMT criteria when appropriate
- To assess biological activity of AVE1642 in combination with Velcade® on malignant plasma cells collected from bone marrow aspirates: saturation and down-regulation of the insulin-like growth factor 1 receptor (IGF-1R) and activity on the signalization pathway of the IGF-1 system (pAkt, pErk) when feasible
- To detect immunogenicity reaction (HAHA)
- To characterize PK and PD profile of a low dose (0.5 mg/kg) of AVE1642 expected to be non biologically active
研究概览
研究类型
介入性
注册 (实际的)
26
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Multiple myeloma confirmed by bone marrow aspirate or biopsy
- Patient had to have relapsed and/or refractory multiple myeloma after at least 1 standard therapy, and have demonstrated disease progression
- Previous exposure to Velcade was allowed, provided no DLTs of Grade 3 or above had been observed during previous treatment (for Part 2 of the study only)
Exclusion Criteria:
- Prior therapy with any IGF-1 system targeting compound
- History of allogenic stem cell transplantation in case of concomitant immunosuppressive therapy within 6 months before study entry. Patients having undergone autologous stem cell transplantation(s) may have been included in the study
- History of organ transplant and any patient receiving long term systemic immunosuppressive therapy
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：AVE1642/ AVE1642 with Velcade
|
For Part 1, AVE1642 was administered on Day 1 and then every three weeks intra-venously with the dose escalation step starting at 3 mg/kg/infusion with a classical dose escalation schema of 3+3.
For Part 2, AVE1642 was administered at doses ranging from 0.5 mg/kg to 12 mg/kg
For Part 2 ONLY, fixed dose of 1.3 mg/m² administered on Days 1, 4, 8, and 11.
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
definition of the Selected Dose (SD)
大体时间：2 years
|
Selected Dose will be based on the AVE1642 clearance /IGF-1 plateaus and on safety (less than 33% of pts with dose limiting toxicity (DLT)when administered as single agent in a first part of the study.
The safety and pharmacokinetics of the regimen in combination with bortezomib will be assessed in the second part of the study
|
2 years
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Assess the efficacy (complete, partial, minimal responses and stabilizations)
大体时间：2 years
|
According to the European Group for Blood and Marrow Transplantation (EBMT) criteria when appropriate (e.g.
baseline M Protein, % Plasma Cells in Bone Marrow,skeletal disease status and at least one evaluable post-baseline assessment)
|
2 years
|
|
Pharmacokinetic drug interaction between AVE1642 and Velcade (part 2)
大体时间：Day 22
|
Day 22
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
赞助
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2006年9月1日
初级完成 (实际的)
2008年9月1日
研究完成 (实际的)
2008年9月1日
研究注册日期
首次提交
2010年10月29日
首先提交符合 QC 标准的
2010年11月2日
首次发布 (估计)
2010年11月3日
研究记录更新
最后更新发布 (估计)
2010年11月3日
上次提交的符合 QC 标准的更新
2010年11月2日
最后验证
2010年10月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.