Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, or Relapsed B-Cell Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00764517
First received: October 1, 2008
Last updated: January 15, 2014
Last verified: January 2014
  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 2014 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00764517

Locations
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
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: January 15, 2014
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 September 14, 2014