This phase II trial studies the side effects and best dose of venetoclax and romidepsin to see how well it works in treating patients with mature T-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Venetoclax and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To assess the safety and tolerability of the combination of venetoclax with romidepsin, including the dose ramp-up, in adults with relapsed or refractory mature T-cell lymphoma. (Safety Lead-in) II. To estimate the efficacy as measured by the overall response rate (ORR) of venetoclax in patients with relapsed or refractory mature T-cell lymphoma. (Phase 2) SECONDARY OBJECTIVES: I. To evaluate the complete response rate, duration of response, time to response, overall survival and progression free survival associated with venetoclax and romidepsin in relapsed/refractory mature T-cell lymphoma. (Phase 2) II. To further characterize the safety and toxicities of venetoclax and romidepsin combination in relapsed/refractory mature T-cell lymphoma. (Phase 2) EXPLORATORY OBJECTIVES: I. To determine BCL2 protein expression in base line treatment tumor samples and correlatieon with response. II. To determine changes in Bcl-2 gene expression in pre- and post-treatment tumor samples of mature T- cell lymphoma. OUTLINE: This is a safety lead-in dose-escalation study, followed by a phase II study. Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 and romidepsin intravenously (IV) on days 1, 8, and 15. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
City of Hope Medical Center
Duarte, California, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Number of Patients With Grade 3 or Above Toxicities
Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0. During the first 2 cycles, all grades of toxicity will be collected. After cycle 2, only the highest grade of any toxicity will be collected for each cycle during protocol treatment and for the period of safety follow-up after end of treatment.
Time frame: Up to 30 days post-treatment, an average of 4 months.
Overall Survival at 100 Days
Overall survival (OS) was measured from start of the study treatment to death from any cause. OS to be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error.
Time frame: From the start of study treatment up to 100 days
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