Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma
2017年9月21日 更新者：AHS Cancer Control Alberta
Phase I Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma
The combination of PARP inhibitor (ABT-888) with a proteasome inhibitors (bortezomib) have demonstrated significant anti-myeloma effects in preclinical lab and animal studies.
The goal of this phase I trial is to evaluate in patients with relapsed or refractory multiple myeloma the safety, toxicity profile and tolerability of ABT-888 (Veliparib) administered on a schedule including twice daily oral dosing for 14 days followed by 1 week rest in combination with standard dosing of Bortezomib.
研究概览
详细说明
This is a dose-finding / dose escalation phase I trial of ABT-888 (Veliparib) in combination with Bortezomib and Dexamethasone in patients with relapsed or refractory multiple myeloma. ABT-888 is given orally (PO) twice daily (every 12 hours) for 14 days in a 21 days cycle.
First dose to be given within 1 hour of Bortezomib on day 1. Planned starting dose is 20 mg PO every 12 hours. Starting dose escalation is planned until an MTD is reached.
研究类型
介入性
注册 (实际的)
19
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。
学习地点
-
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Alberta
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Calgary、Alberta、加拿大、T2N 4N2
- Tom Baker Cancer Centre
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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:
- Confirmed diagnosis of multiple myeloma.
- Measurable disease, according to the International Myeloma Working Group criteria.
- ECOG performance status 0, 1 or 2.
- Patients must have received prior treatment for MM and have relapsed or progressed on prior therapy; no limit on number of prior treatment regimens, but prior treatment must be completed 2 weeks prior to registration. Prior exposure to Bortezomib is not an exclusion criteria as long as patients did not progress or relapse while receiving or within 3 months of completing trt with bortezomib
- Prior radiation, completed at least 4 weeks prior to registration, is permitted.
- Adequate marrow reserve, liver and renal function
Exclusion Criteria:
- patients with a history of other malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, prostate cancer with stable PSA for > 3 years, or other solid tumours curatively treated with no evidence of disease for > 5 years.
- Patients with preexisting grade 2 (or higher) sensory neuropathy or grade 1 sensory neuropathy with neuropathic pain.
- Pregnant or lactating women
- Patients receiving concurrent treatment with other anti-cancer therapy any other investigational agents.
- Active or uncontrolled infections
- Patient with known documented congenital or acquired risk factor for thromboembolic event
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive
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：不适用
- 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 |
|---|---|
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实验性的：ABT-888/Bortezomib
Patients will be on a treatment schedule including twice daily oral dosing for 14 days followed by 1 week rest in combination with standard dosing of Bortezomib and Dexamethasone in a 21 days cycle for a total of 14 cycles.
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ABT-888 is given orally (PO) twice daily (every 12 hours) for 14 days in a 21 days cycle.
First dose to be given within 1 hour of Bortezomib on day 1.
Planned starting dose is 20 mg PO every 12 hours.
Starting dose escalation is planned until an MTD is reached.
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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 |
|---|---|---|
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Determine the maximum tolerated dose (MTD) of ABT-888.
大体时间：21 Day Cycle
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Study follows a modified dose escalation scheme with a 3+3 design (3 to 6 patients per dose level or cohort).
Only the ABT-888 dose will be escalated with a maximum dose of ABT-888 of 100 mg PO BID.
If >1 out 6 patients at any dose level suffer dose limiting toxicity, then dose escalation is stopped, and this dose is declared as MTD. 3 additional patients will be entered at the next lowest dose level.
The recommended phase 2 dose is defined as the dose level with ≤ 1 out of 6 patients experiencing DLTs at the highest dose level below the MTD.
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21 Day Cycle
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Identify the Dose Limiting Toxicities (DLT) of ABT-888
大体时间：21 Day Cycle
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All adverse events, including DLTs, are graded according to the NCI CTCAE, v4.0.
A DLT is defined as any grade 3 or higher non-hematologic toxicity, or any grade 4 hematologic toxicity, considered by the investigator to be related to the study drugs and occurring during Days 1-22 of Cycle 1.
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21 Day Cycle
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Activity Objective - Preliminary assessment of the anti-tumor activity of ABT-888
大体时间：21 day cycle
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Response to study drugs is assessed at the end of each cycle according to the International Myeloma Working Group (IMWG) response criteria.
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21 day cycle
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Exploratory Objective - Preliminary assessment of potential biomarkers
大体时间：24 months
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Gene expression profiling is performed at baseline and compared between responders versus non-responders in order to identify a "treatment response signature".
2.5 mg of RNA will be extracted from plasma cells sorted from pre-treatment (D1, cycle 1) (n=20) and post-treatment (D11, cycle 1) (n=20) bone marrow aspirates collected from patients treated in the extension cohort.
cRNAs will be hybridized onto the U133 Plus 2.0 gene chips and raw data files acquired using Affymetrix Microarray Suite version 5.1 software and analyzed with the Partek Genomics Suite v6.4.
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24 months
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Exploratory Objective - Determine in vivo the effect of ABT-888 on PARP inhibitors.
大体时间：24 Months
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Poly-ADP-ribose (PAR) levels are measured in sorted CD138+ plasma cells from pre-ABT-888 treatment on day 1 cycle1, as well as post ABT-888 treatment (within 4-6 hours) on days 4 and 11.
PAR levels will be measured by standardized ELISA assays (HT PARP in vivo Pharmacodynamic Assay II™, Trevigen).
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24 Months
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Determine invivo the effects of Bortezomib on the plasma cells DNA genes expression and function
大体时间：24 Months
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Gene expression profiling is performed at baseline prior to treatment with bortezomib and on days 4 and 11 post bortezomib treatment.
2.5 mg of RNA will be extracted from plasma cells sorted from bone marrow aspirates collected from patients treated on trial.
cRNAs will be hybridized onto the U133 Plus 2.0 gene chips and raw data files acquired using Affymetrix Microarray Suite version 5.1 software and analyzed with the Partek Genomics Suite v6.4.
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24 Months
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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。
调查人员
- 学习椅：Nizar J Bahlis, M.D.、Tom Baker Cancer Centre, University of Calgary
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 (实际的)
2011年10月1日
初级完成 (实际的)
2015年2月1日
研究完成 (实际的)
2015年2月10日
研究注册日期
首次提交
2011年11月16日
首先提交符合 QC 标准的
2011年12月16日
首次发布 (估计)
2011年12月20日
研究记录更新
最后更新发布 (实际的)
2017年9月25日
上次提交的符合 QC 标准的更新
2017年9月21日
最后验证
2017年9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.