This randomized phase I trial studies the side effects and the best dose of carfilzomib when given together with or without romidepsin in treating patients with stage IA-IVB cutaneous T-cell lymphoma. Carfilzomib and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving carfilzomib alone is more effective than when given together with romidepsin.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of carfilzomib, both as a single agent as well as in combination with romidepsin, in patients with cutaneous T-cell lymphoma (CTCL). SECONDARY OBJECTIVES: I. Overall response rate (ORR). II. Duration of response. III. Time to progression (TTP). TERTIARY OBJECTIVES: I. Measure proteasome activity concurrently in peripheral blood mononuclear cells (PBMCs) and tumor tissue biopsy specimens in order to gather pilot data on proteasome inhibition in CTCL patients treated with carfilzomib alone as well as carfilzomib with romidepsin. OUTLINE: This is a dose-escalation study of carfilzomib. Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16. ARM B: Patients receive carfilzomib as in Arm A and romidepsin IV over 4 hours on days 1, 8, and 15. In both arms, treatment repeats every 28 days for at least 2-4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Northwestern University
Chicago, Illinois, United States
Number of Patients With Dose Limiting Toxicities (DLTs)
To determine the maximum tolerated dose (MTD) by assessing the adverse events experienced by patients of both carfilzomib alone and when taken with romidepsin for dose limiting toxicities (DLT) on days 1 and 15 of the first 28 days of treatment. Toxicities will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. DLT is defined as any of the following: Grade ≥ 2 neuropathy with pain Grade ≥ 3 non-hematologic toxicity Grade ≥ 3 nausea, vomiting, or diarrhea not controlled Grade ≥ 4 fatigue persisting for \> 7 days Grade 4 neutropenia (ANC \< 500/mm3) occurring for \>7 days Febrile neutropenia \[ANC \< 1000/mm3 with fever Grade ≥ 3 thrombocytopenia persisting for \> 7 days Grade ≥ 3 thrombocytopenia associated with bleeding Any toxicity requiring a dose reduction within Cycle 1 Inability to receive Cycle 2, Day 1 dose due to drug related toxicity persisting from Cycle 1 or drug-related toxicity newly encountered on Cycle 2, Day 1
Time frame: During the first 28 days (1 cycle=28 days) of treatment.
Overall Response Rate (ORR) of the Disease When Treated With Carfilzomib Alone and When Taken With Romidepsin
Overall Response Rate (ORR) is defined as number of patients who's best response is complete response or partial response. Response will be categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The overall response rate of the study treatment will be evaluated based on skin biopsy, CT scans, and blood tests at the beginning of the study as well as every 56 days (2 cycles).
Time frame: Baseline and every 56 days (2 cycles) while on treatment and up to 4 cycles
Duration of Response of the Disease When Treated With Carfilzomib Alone and When Taken With Romidepsin
Duration of response will be defined as the time from the point at which response is achieved until the point of disease progression. The duration of response of the study treatment will be evaluated based on skin biopsy, CT scans, and blood tests at the beginning of the study as well as every 56 days (2 cycles).
Time frame: Baseline and every 56 days (2 cylces) until disease progression
Time to Progression (TTP) of the Disease When Treated With Carfilzomib Alone and When Taken With Romidepsin
The time to progression (TTP) will be measured as the time from the first dose of study therapy until the point at which disease is determined to have progressed or patients discontinue therapy for toxicity. To measure time to progression, the study treatment will be evaluated based on skin biopsy, CT scans, and blood tests at the beginning of the study as well as every 56 days (2 cycles).
Time frame: Baseline and every 56 days (2 cycles) until disease progression or toxicity call for discontinuation of treatment
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