Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Relapsed Chronic Lymphocytic Leukemia, or Relapsed B Cell Non-Hodgkin's Lymphoma
|Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Indolent Adult Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma||Drug: Cladribine Other: Laboratory Biomarker Analysis Biological: Rituximab Drug: Vorinostat||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Vorinostat (SAHA), Cladribine, and Rituximab (SCR) in Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, and Relapsed B Cell Non-Hodgkin Lymphoma|
- Objective response rate [ Time Frame: 2 years ]Assessed per the revised Cheson criteria. Response definitions per revised International Working Group Response Criteria. 95% confidence interval will be provided.
- Toxicities as assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 6 months ]
- Activation of genes or miRNAs [ Time Frame: Up to 2 years ]
- DNA methylation/histone deacetylation [ Time Frame: Baseline ]A logrank test will be used to compare progression-free survival (PFS) and overall survival (OS) between patients with and without DNA methylation and/or histone deacetylation. A chi-square test will be used to compare the objective response between patients with and without DNA methylation and/or histone deacetylation status.
- Event-free survival [ Time Frame: 2 years ]Estimated using the Kaplan-Meier method.
- Global and gene specific changes in transcription of mRNAs and MiRNAs [ Time Frame: Up to 2 years ]
- Progression-free survival [ Time Frame: 2 years ]Estimated using the Kaplan-Meier method.
|Study Start Date:||August 2008|
|Study Completion Date:||March 2017|
|Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (SCR regimen)
Patients receive vorinostat PO on days 1-14, cladribine IV over 2 hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesBiological: Rituximab
Other Names:Drug: Vorinostat
I. Determine objective response rates of the SCR regimen (vorinostat, cladribine, and rituximab) in B-cell malignancies.
II. Determine the tolerability and toxicities of the SCR regimen.
I. Evaluate progression free survival in patients treated with SCR. II. Estimate event free survival for patients treated with SCR. III. Determine the contribution (if any) of deoxyribonucleic acid (DNA) methylation/histone deacetylation to disease progression and/or response to SCR combination chemotherapy.
IV. Perform scientific correlates to determine if SCR treatment a) is associated with global and gene specific changes in transcription of messenger ribonucleic acid (mRNA)s and micro ribonucleic acid (MiRNA)s b) is acting as an inhibitor of DNA methylation c) is activating or silencing specific genes or miRNAs.
Patients receive vorinostat orally (PO) on days 1-14, cladribine intravenously (IV) over 2 hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years and then every 6 months thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00764517
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|Principal Investigator:||Stephen Spurgeon||OHSU Knight Cancer Institute|