A Phase I/II Trial of Rituximab, Bendamustine, and Obatoclax in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Maximum tolerable dose, defined as the dose level beneath which 2 or more of 6 patients experience DLT (phase I)
研究概览
简要总结
This phase I/II trial is studying the side effects and the best dose of obatoclax mesylate when given together with rituximab and bendamustine hydrochloride to see how well it works compared with rituximab and bendamustine hydrochloride alone in treating patients with relapsed or refractory non-Hodgkin lymphoma. Obatoclax mesylate may stop the growth of cancer cells by blocking some of the proteins needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with rituximab and bendamustine hydrochloride may kill more cancer cells
详细描述
PRIMARY OBJECTIVES:
I. To determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of the combination of obatoclax mesylate, rituximab, and bendamustine hydrochloride in patients with relapsed or refractory, indolent, B-cell non-Hodgkin lymphoma (phase I).
II. To define the qualitative and quantitative toxicities of the combination of obatoclax mesylate, rituximab, and bendamustine (phase I).
III. To detect an improvement in median progression-free survival (PFS) from 6 to 12 months with the addition of obatoclax mesylate to rituximab and bendamustine hydrochloride in patients with indolent B-cell non-Hodgkin lymphoma (phase II).
SECONDARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 confirmed indolent B-cell non-Hodgkin lymphoma (NHL), including any of the following subtypes recognized by WHO classification:
- •Marginal zone lymphoma
- •Lymphoplasmacytic lymphoma
- •Follicular lymphoma
- •Mantle cell lymphoma
- •Transformed lymphoma from a low-grade, indolent NHL allowed provided patient has received ≥ 1 prior therapy for indolent disease
- •Must have received ≥ 1 prior therapy
- •Relapsed disease after autologous or allogeneic stem cell transplantation (SCT) allowed (phase I)
- •No relapse after allogeneic SCT (phase II)
- •No known CNS lymphoma
- •ECOG performance status 0-2
- •ANC ≥ 1,000/µL
- •Platelet count ≥ 50,000/µL
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN
- •Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min
- •Not pregnant or nursing
- •Fertile patients must use effective contraception prior to and for the duration of study participation
- •No active hepatitis B infection
- •Patients with a history of hepatitis B (surface antigen or core antibody positive) must take lamivudine or equivalent during study therapy
- •No history of documented human anti-globulin antibodies, or a history of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab, bendamustine hydrochloride, or obatoclax mesylate
- •No uncontrolled intercurrent illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness and/or social situations that would limit compliance with study requirements
- •HIV infection allowed provided patient meets the following criteria:
- •No evidence of co-infection with hepatitis B or C
- •CD4 cell count ≥ 400/mm³
- •No evidence of resistant strains of HIV
- •HIV viral load ≤ 10,000 copies HIV RNA/mL for patients not on anti-HIV combination antiretroviral therapy OR HIV viral load ≤ 50,000 copies HIV RNA/mL for patients on anti-HIV therapy
- •No history of AIDS-defining conditions
- •No active secondary malignancy except for non-melanomatous skin cancer
- •No other concurrent investigational agents
- •Prior bendamustine hydrochloride allowed provided patient has completed a bendamustine-containing regimen within the past 6 months and achieved a partial response or better
- •More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive obatoclax mesylate IV over 3 hours on days 1-3, rituximab IV over 4-8 hours on day 1, and bendamustine hydrochloride IV over 30 minutes on days 1-2.
干预措施: bendamustine hydrochloride (Drug)
Arm I
Patients receive obatoclax mesylate IV over 3 hours on days 1-3, rituximab IV over 4-8 hours on day 1, and bendamustine hydrochloride IV over 30 minutes on days 1-2.
干预措施: obatoclax mesylate (Drug)
Arm I
Patients receive obatoclax mesylate IV over 3 hours on days 1-3, rituximab IV over 4-8 hours on day 1, and bendamustine hydrochloride IV over 30 minutes on days 1-2.
干预措施: rituximab (Biological)
Arm II
Patients receive rituximab and bendamustine hydrochloride as in arm I.
干预措施: bendamustine hydrochloride (Drug)
Arm II
Patients receive rituximab and bendamustine hydrochloride as in arm I.
干预措施: rituximab (Biological)
结局指标
主要结局
Maximum tolerable dose, defined as the dose level beneath which 2 or more of 6 patients experience DLT (phase I)
时间窗: 28 days
Graded using CTCAE version 4 criteria. DLTs are defined as grade 3-4 neutropenia or thrombocytopenia that persists beyond day 42; grade 4 febrile neutropenia or infection; grade 3 febrile neutropenia or infection that fails to resolve within 7days, grade 3-4 somnolence, ataxia, or confusion that requires inpatient admission on day 1 for observation and prevents patient discharge from outpatient clinic, or other grade 3-4 non-hematologic toxicity excluding infection.
Change in median progression-free survival (PFS) (phase II)
时间窗: From 6 to 12 months
Estimated using the method of Kaplan-Meier.
次要结局
- Overall objective response rate (phase II)(Up to 3 years)
- PFS (phase II)(From the date of start of therapy to disease progression or death, whichever occurs first, assessed at 2 years)