Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, or Relapsed B-Cell Non-Hodgkin Lymphoma
This study is currently recruiting participants.
Verified March 2013 by OHSU Knight Cancer Institute
Sponsor:
OHSU Knight Cancer Institute
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00764517
First received: October 1, 2008
Last updated: March 28, 2013
Last verified: March 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia Lymphoma |
Biological: rituximab Drug: cladribine Drug: vorinostat Other: laboratory biomarker analysis |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Further study details as provided by OHSU Knight Cancer Institute:
Primary Outcome Measures:
- Maximum tolerated dose of vorinostat [ Time Frame: Daily on days 1-14 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- 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 ]
| Estimated Enrollment: | 58 |
| Study Start Date: | September 2008 |
| Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 |
Biological: rituximab
375 mg/m2 IV weekly for cycle 1, then once per cycle on day 3
Drug: cladribine
5 mg/m2 on days 1-5 via 2 hour infusion
Other Name: 2-chloro-2-deoxyadenosine
Drug: 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
Other: 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.
|
Detailed Description:
OBJECTIVES:
Primary
- 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).
Secondary
- 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Diagnosis of the following B-cell malignancies:
- Chronic lymphocytic leukemia (CLL)
- Non-Hodgkin lymphoma (NHL), including mantle cell lymphoma
Newly diagnosed or relapsed/refractory disease
- Patients enrolled in phase I must have relapsed or refractory disease
- Patients enrolled in phase II who have NHL (excluding mantle cell lymphoma) must have relapsed or refractory disease
PATIENT CHARACTERISTICS:
- Not specified
PRIOR CONCURRENT THERAPY:
- Not specified
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00764517
Locations
| United States, Oregon | |
| OHSU Knight Cancer Institute | Recruiting |
| Portland, Oregon, United States, 97239-3098 | |
| Contact: Clinical Trials Hotline 503-494-1080 trials@ohsu.edu | |
| Principal Investigator: Stephen Spurgeon, MD | |
| United States, Pennsylvania | |
| Penn State Hershey Cancer Institute | Recruiting |
| Hershey, Pennsylvania, United States, 17033 | |
| Contact: Clinical Trials Hotline 503-494-1080 trials@ohsu.edu | |
| Sub-Investigator: Elliot Epner, MD, PhD | |
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
| Principal Investigator: | Stephen Spurgeon, MD | OHSU Knight Cancer Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | OHSU Knight Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00764517 History of Changes |
| Other Study ID Numbers: | CDR0000615128, P30CA069533, OHSU-4180, HEM-08002-L, MERCK-OHSU-4180 |
| Study First Received: | October 1, 2008 |
| Last Updated: | March 28, 2013 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by OHSU Knight Cancer Institute:
|
B-cell chronic lymphocytic 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 recurrent mantle cell lymphoma stage I mantle cell lymphoma contiguous stage II mantle cell lymphoma noncontiguous stage II mantle cell lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma recurrent adult Burkitt lymphoma recurrent adult diffuse large cell lymphoma |
recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma recurrent adult lymphoblastic lymphoma recurrent adult grade III lymphomatoid granulomatosis Waldenstrom macroglobulinemia extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Rituximab Vorinostat Cladribine Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 19, 2013