Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, or Relapsed B-Cell Non-Hodgkin Lymphoma
RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cladribine, 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 vorinostat together with cladribine and rituximab may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of vorinostat when given together with cladribine and rituximab and to see how well it works in treating patients with mantle cell lymphoma, chronic lymphocytic leukemia, or relapsed B-cell non-Hodgkin lymphoma.
Other: laboratory biomarker analysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Vorinostat (SAHA), Cladribine, and Rituximab (SCR) in Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, and Relapsed B Cell Non-Hodgkin's Lymphoma|
- Maximum tolerated dose of vorinostat [ Time Frame: Daily on days 1-14 ] [ Designated as safety issue: Yes ]
- Response rates [ Time Frame: Median time to response was 26 days (range 28 to 171 days) ] [ Designated as safety issue: No ]
- Safety and efficacy [ Time Frame: Safety:Labs weekly for the first cycle then 2x/month, clinic visits every other week for cycle 1, then monthly (on day 1). Efficacy: Screening evaluations (no later than 42 days prior to study enrollment) ] [ Designated as safety issue: Yes ]
- Progression-free survival [ Time Frame: One year after study enrollment with plan for additional analysis at two years. ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: One year after study enrollment with plan for additional analysis at two years. ] [ Designated as safety issue: No ]
|Study Start Date:||September 2008|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Rituximab, Cladribine, Vorinostat
Rituximab: 375 mg/m2 IV weekly for cycle 1, then once per cycle on day 3
Cladribine: 5 mg/m2 on days 1-5 via 2 hour infusion
Vorinostat: 400 mg daily on days 1-14, will be dose reduced as needed for dose limiting toxicities per protocol with the minimum dose allowed being 100 mg on days 1-7
375 mg/m2 IV weekly for cycle 1, then once per cycle on day 3Drug: cladribine
5 mg/m2 on days 1-5 via 2 hour infusion
Other Name: 2-chloro-2-deoxyadenosineDrug: vorinostat
400 mg daily on days 1-14, will be dose reduced as needed for dose limiting toxicities per protocol with the minimum dose allowed being 100 mg on days 1-7Other: laboratory biomarker analysis
Samples will be collected prior to the start of the trial and then at pre-determined regular intervals during the trial. These samples will be de-identified and sent to Dr. Elliot Epner's lab (PI at Penn State) for DNA and RNA extraction. Samples will then be sent to Dr. Samir Parekh's lab at the Albert Einstein College of Medicine to be run using the HELP (HpaII tiny fragment Enrichment by Ligation mediated PCR) assay. Ultimately, changes in the DNA methylation will be correlated with response to therapy and/or disease progression and patient outcomes.
- To determine the maximum tolerated dose of vorinostat when administered in combination with cladribine and rituximab in patients with mantle cell lymphoma, chronic lymphocytic leukemia (CLL), or relapsed B-cell non-Hodgkin lymphoma (NHL).
- To determine the response rate in patients treated with this regimen.
- To determine the safety and efficacy of this regimen in these patients.
- To determine the progression-free survival of patients treated with this regimen.
- To determine the overall survival of patients treated with this regimen.
- To collect blood samples for genetic testing to help understand how NHL and CLL are affected by vorinostat alone and by vorinostat in combination with cladribine and rituximab.
OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.
- Phase I: Patients receive oral vorinostat on days 1-14 and cladribine on days 1-5. Patients also receive rituximab on days 3, 10, 17, and 24 of course 1 and on day 3 of all subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive vorinostat (at the maximum tolerated dose determined in phase I), cladribine, and rituximab as in phase I.
Blood samples are collected periodically for laboratory studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00764517
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239-3098|
|United States, Pennsylvania|
|Penn State Hershey Cancer Institute|
|Hershey, Pennsylvania, United States, 17033|
|Principal Investigator:||Stephen Spurgeon, MD||OHSU Knight Cancer Institute|