NCT00612612

Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

A Phase 1 Study of Obatoclax Mesylate (GX15-070MS) in Combination With Fludarabine-Based Chemoimmunotherapy in Previously Treated Patients With B-Cell Chronic Lymphocytic Leukemia (B-CLL)

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Obatoclax may stop the growth of chronic lymphocytic leukemia by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving obatoclax together with fludarabine and rituximab may kill more cancer cells. This phase I trial is studying the side effects and best dose of obatoclax when given together with fludarabine and rituximab in treating patients with B-cell chronic lymphocytic leukemia.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose of obatoclax mesylate in combination with fludarabine phosphate-rituximab (FR) in patients with relapsed chronic lymphocytic leukemia. SECONDARY OBJECTIVES: I. To evaluate toxicity of obatoclax mesylate in combination with FR in this patient population. II. To determine objective response rate and progression-free survival of obatoclax mesylate in combination with FR. III. To correlate levels of anti-apoptotic Bcl-2 family members with drug response. IV. To determine whether apoptosis is induced via the mitochondrial pathway in response to obatoclax mesylate and further enhanced by FR. OUTLINE: This is a dose-escalation study of obatoclax mesylate. Patients receive obatoclax mesylate IV over 3 hours on days 1 and 3, fludarabine IV over 20-30 minutes on days 1-5, and rituximab IV over 4 hours on day 1 (days 1 and 3 of course 1 only). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo peripheral blood collection for correlative studies. Samples are analyzed for expression of pro- and anti-apoptotic Bcl-2 family members by western blot; apoptosis induction by measurement of lymphocyte count, Annexin V staining, and Caspase and PARP cleavage; activated Bax by immunoprecipitation; and Bax promoter polymorphism by PCR amplification and direct sequencing. After completion of study therapy, patients are followed every 6 months.

Conditions

• B-cell Chronic Lymphocytic Leukemia
• Leukemia
• Prolymphocytic Leukemia
• Refractory Chronic Lymphocytic Leukemia
• Stage I Chronic Lymphocytic Leukemia
• Stage II Chronic Lymphocytic Leukemia
• Stage III Chronic Lymphocytic Leukemia
• Stage IV Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	obatoclax mesylate	Given IV
DRUG	fludarabine phosphate	Given IV
BIOLOGICAL	rituximab	Given IV
OTHER	laboratory biomarker analysis	Correlative study

Timeline

• Start date: 2008-01-01
• Primary completion: 2013-07-01
• First posted: 2008-02-11
• Last updated: 2013-09-30

Locations

1 site across 1 country: United States