Phase I Study of GX15-070 (NSC # 729280) and Bortezomib in Aggressive Relapsed/Recurrent Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of obatoclax mesylate when administered with bortezomib
研究概览
简要总结
Obatoclax may stop the growth of non-Hodgkin lymphoma by blocking blood flow to the cancer. Bortezomib and obatoclax 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. 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 aggressive relapsed or recurrent non-Hodgkin lymphoma.
详细描述
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose of obatoclax mesylate when administered with bortezomib in patients with aggressive relapsed or recurrent non-Hodgkin lymphoma.
II. To describe the toxicities of this regimen at each dose studied in these patients.
III. To characterize the pharmacokinetic behavior of this regimen in these patients.
IV. To obtain preliminary information regarding the effect of obatoclax mesylate on several apoptotic regulatory pathways.
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
- •Histologically or cytologically confirmed relapsed or refractory non-Hodgkin lymphoma for which standard curative or palliative measures do not exist or are no longer effective, including any of the following subtypes:
- •Follicular grade I, II, or III lymphoma
- •Marginal zone lymphoma
- •Mantle cell lymphoma
- •Diffuse large B cell lymphoma
- •Small lymphocytic lymphoma
- •Must have had at least one prior chemotherapeutic regimen:
- •Steroids or rituximab alone or local radiotherapy do not count as regimens
- •Tositumomab or ibritumomab tiuxetan allowed as regimens
- •Clear evidence of disease progression or lack of response after the most recent therapy, including rituximab or local radiotherapy, is required
- •At least 3 months since prior autologous stem cell transplantation and relapsed (>= 1 year since prior allogeneic transplantation and relapsed) and no active related infections (i.e., fungal or viral)
- •In the case of allogeneic transplantation relapse, there should be no active acute graft-versus-host disease (GVHD) of any grade and no chronic GVHD other than mild skin, oral, or ocular GVHD not requiring systemic immunosuppression
- •No known active brain metastases, other neurological disorders/dysfunction or history of seizure disorder, or other neurological dysfunction
- •Karnofsky performance status 60-100%
- •Life expectancy > 3 months
- •Total bilirubin normal
- •AST and ALT =< 2.5 times upper limit of normal
- •Creatinine normal or creatinine clearance >= 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective double-barrier contraception during and for 3 months after the last dose of obatoclax mesylate
- •At least 4 weeks since prior radiotherapy
- •More than 2 days since prior steroids
- •More than 2 weeks since prior low-dose chlorambucil
- •WBC >= 3,000/mm^3
- •ANC >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •At least 2 weeks since prior valproic acid
排除标准
- •Uncontrolled concurrent medical condition or illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia including QTc > 450 msec
- •Patients who are intolerant or refractory to prior treatment with bortezomib (refractory is defined as no response to prior treatment with bortezomib)
- •Chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
- •Rituximab within the past 3 months (unless there is evidence of progression)
- •Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Other concurrent investigational agents
- •Combination antiretroviral therapy for HIV-positive patients
- •No history of allergic reactions attributed to bortezomib, polyethylene glycol (PEG 300), or polysorbate 20
- •No psychiatric illness or social situation that would limit compliance with study requirements
研究组 & 干预措施
Treatment (obatoclax mesylate, bortezomib)
Patients will receive a 3-hour infusion of obatoclax and an infusion of bortezomib once a week for 4 weeks
干预措施: obatoclax mesylate (Drug)
Treatment (obatoclax mesylate, bortezomib)
Patients will receive a 3-hour infusion of obatoclax and an infusion of bortezomib once a week for 4 weeks
干预措施: bortezomib (Drug)
Treatment (obatoclax mesylate, bortezomib)
Patients will receive a 3-hour infusion of obatoclax and an infusion of bortezomib once a week for 4 weeks
干预措施: laboratory biomarker analysis (Other)
Treatment (obatoclax mesylate, bortezomib)
Patients will receive a 3-hour infusion of obatoclax and an infusion of bortezomib once a week for 4 weeks
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum tolerated dose of obatoclax mesylate when administered with bortezomib
时间窗: 35 days
Defined as the highest dose tested in which fewer than 33% of patients experienced DLT attributable to the study drug(s), when at least six patients were treated at that dose and are evaluable for toxicity. Graded according to the NCI CTCAE, Version 3.0.
次要结局
- Toxicity as assessed by NCI CTCAE version 3.0(Up to 26 weeks after completion of study treatment)
- Pharmacokinetics of obatoclax mesylate when administered with bortezomib(Dose 1 of course 1, pre-infusion, 1 and 2 hours into the infusion, immediately prior to the end of the infusion, then at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, and 168 hours)