A Phase I/II Trial of Obatoclax Mesylate (GX15-070MS) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Number of Dose-limiting Toxicity (DLT) Incidents (Phase I)
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of obatoclax when given together with bortezomib and to see how well they work in treating patients with relapsed or refractory multiple myeloma. Obatoclax and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obatoclax together with bortezomib may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose and recommended phase II dose of obatoclax mesylate when given in combination with bortezomib in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the response rate (complete response, partial response, and very good partial response) in patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
I. To determine the duration of progression-free and overall survival of these patients.
II. To evaluate the incidence of toxicities of this regimen in these patients. III. To explore the utility of genetic markers based on initial evidence that they are predictive of drug responsiveness and/or successful target inhibition.
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
- •Symptomatic multiple myeloma, meeting the following criteria at original diagnosis:
- •Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
- •Symptomatic disease (e.g.,anemia, hypercalcemia, bone disease, or renal dysfunction) that requires the initiation of therapy
- •Measurable diseases assessed by one of the following:
- •Monoclonal plasma cells detectable in the bone marrow
- •Monoclonal serum spike detectable by serum protein electrophoresis or immunofixation
- •Monoclonal protein detectable in the urine by electrophoresis or immunofixation
- •Abnormal levels of the serum free light chains with an abnormal ratio between kappa and lambda
- •Progressive disease after ≥ 1 prior therapy for myeloma
- •Previously treated with ≤ 10 courses (30 weeks) of bortezomib and had no disease progression during therapy OR completed bortezomib therapy within the past 6 weeks
- •No prior discontinuation of bortezomib therapy due to drug intolerance
- •No known brain metastases
- •No intracranial edema, intracranial metastasis, or active epidural disease
- •Patients with lytic lesions of the cranium secondary to myeloma are eligible
- •ECOG performance status 0-2
- •Life expectancy > 6 months
- •ANC ≥ 1,000/mm³
- •Platelet count ≥ 50,000/mm³
- •Bilirubin normal
- •AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- •Creatinine ≤ 2 times ULN
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No peripheral neuropathy > NCI toxicity grade 2
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to obatoclax mesylate or bortezomib
- •No concurrent uncontrolled illness including, but not limited to the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia, including QTc > 450 msec
- •Psychiatric illness/social situations that would limit compliance with study requirements
- •No history of seizure disorder
- •No other neurological disorder or dysfunction that, in the opinion of the investigator, would confound the evaluation of neurologic and other adverse events associated with obatoclax mesylate
- •At least 14 days since prior chemotherapy and recovered
- •More than 28 days since prior experimental drugs and/or investigational agents
- •No concurrent CYP interactive medications
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent anticancer therapy
- •Growth factors and bisphosphonates are allowed as medically indicated
- •Prednisone (≤ 10 mg per day) allowed provided there has been no dose increase within the past 2 weeks
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
Patients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: obatoclax mesylate (Drug)
Treatment (enzyme inhibitor therapy)
Patients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Treatment (enzyme inhibitor therapy)
Patients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Number of Dose-limiting Toxicity (DLT) Incidents (Phase I)
时间窗: Up to 21 days of every first course
DLT was defined as any events that is determined to be possibly, probably, or definitely related to the combination of bortezomib and GX15-070 (as determined by the investigator) and occurring during the first cycle of treatment, irrespective of whether the toxicity resolved. Hematologic DLT measures were assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via Common Terminology Criteria for Adverse Events (CTCAE) version 3 standard toxicity grading.
Proportion of Patients Who Achieve a Partial Response or Better. (Phase II)
时间窗: From baseline to up to 3 years
In order to be classified as a hematologic response, confirmation of serum monoclonal protein, serum immunoglobulin free light chain (when primary determinant of response) and urine monoclonal protein (when primary determinant of response) results must be made by verification on two consecutive determinations.
次要结局
- Number of Patients Who Have at Least a Partial Response (Phase I)(From baseline to up to 3 years)
- Overall Survival (Phase II)(Time from registration to death due to any cause)
- Time to Treatment Failure (Phase II)(Time from study entry to the date patients end treatment)
- Time to Progression (Phase II)(Time from registration to the time of progression)
- Toxicity as Assessed by the National Cancer Institute (NCI) CTCAE v 3.0 (Phase II)(From baseline to up to 3 years)