This phase II trial studies how well giving vorinostat, cladribine, and rituximab together works in treating patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), or B cell non-Hodgkin's lymphoma (NHL) that has returned after a period of improvement. 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, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving vorinostat together with cladribine and rituximab may kill more cancer cells.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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. OUTLINE: 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
57
OHSU Knight Cancer Institute
Portland, Oregon, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
Objective Response Rate
ORR defined as the percentage of patients who achieved a complete response (CR) or a partial response (PR). Assessed per the revised Cheson criteria. Response definitions per revised International Working Group Response Criteria. 95% confidence interval will be provided. Definitions: Complete response (CR) = disappearance of all evidence of disease; Partial response (PR) = regression of measurable disease and no new sites.
Time frame: 2 years
Toxicities as Assessed Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Toxicity is determined percentage of patients that experienced an adverse event (AE) grade 3 or higher during the time frame, assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade refers to the severity of the AE increasing from Grade 1 to 5. Generally, Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; Grade 5 = Death related to AE.
Time frame: 6 months
Tolerability of Treatment
Tolerability is determined to be the percentage of patients who completed the full duration of treatment (all 6 cycles) regardless of adverse event status. % tolerability shows the rate of patients that tolerated the treatment for the full duration.
Time frame: 6 months
Progression-free Survival
Time from treatment start until disease progression or death. Estimated using the Kaplan-Meier method. A logrank test will be used to compare progression-free survival between Group I and Group II. A p-value less that 0.05 will be considered statistically significant.
Time frame: Up to 5 years
Event-free Survival
Time from treatment start until disease progression, death, or discontinuation of treatment for adverse event (toxicity) Estimated using the Kaplan-Meier method. A logrank test will be used to compare progression-free survival between Group I and Group II. A p-value less that 0.05 will be considered statistically significant.
Time frame: Up to 5 years
Contribution (if Any) of DNA Methylation/Histone Deacetylation
Determine the contribution (if any) of DNA methylation/histone deacetylation to disease progression and/or response to SCR combination chemotherapy. Outcome not evaluated due to technical challenges collecting the data, and lack of budget and personnel to complete the analysis.
Time frame: Up to 2 years
Scientific Correlates
Perform scientific correlates to determine if SCR treatment a) is associated with global and gene specific changes in transcription of mRNAs and MiRNAs b) is acting as an inhibitor of DNA methylation c) is activating or silencing specific genes or miRNAs. Outcome not evaluated due to technical challenges collecting the data, and lack of budget and personnel to complete the analysis.
Time frame: Baseline
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