Phase I Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Determine the maximum tolerated dose (MTD) of ABT-888.
研究概览
简要总结
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.
详细描述
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
- •Confirmed diagnosis of multiple myeloma.
- •Measurable disease, according to the International Myeloma Working Group criteria.
- •ECOG performance status 0, 1 or
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: ABT-888/Bortezomib (Drug)
结局指标
主要结局
Determine the maximum tolerated dose (MTD) of ABT-888.
时间窗: 21 Day Cycle
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.
Identify the Dose Limiting Toxicities (DLT) of ABT-888
时间窗: 21 Day Cycle
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.
次要结局
- Exploratory Objective - Preliminary assessment of potential biomarkers(24 months)
- Activity Objective - Preliminary assessment of the anti-tumor activity of ABT-888(21 day cycle)
- Exploratory Objective - Determine in vivo the effect of ABT-888 on PARP inhibitors.(24 Months)
- Determine invivo the effects of Bortezomib on the plasma cells DNA genes expression and function(24 Months)