This phase I/II trial studies the side effects and best dose of romidepsin and lenalidomide when combined with rituximab and to see how well this combination works in treating patients with B-cell non-Hodgkin lymphoma that has returned (recurrent) or did not respond to treatment (refractory). Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Romidepsin and lenalidomide may stop the growth of cancer cells by blocking enzymes needed for cell growth. Giving rituximab together with romidepsin and lenalidomide may be a better treatment for B-cell non-Hodgkin lymphoma.
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) of the combination of romidepsin, rituximab and lenalidomide in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). (Phase I) II. To assess the overall response rate (ORR) of this combination in patients with transformed follicular lymphoma (FL). (Phase II) SECONDARY OBJECTIVES: I. To assess the toxicity and safety of romidepsin in combination with lenalidomide and rituximab. II. To assess complete response rate (CR), progression free survival (PFS), and overall survival (OS) of this combination in patients with transformed FL. TERTIARY OBJECTIVES: I. To assess the impact of B-cell leukemia/lymphoma 2 (BCL2) mutations on ORR among patients treated with this combination. II. To assess the impact of BCL2 mutations on PFS among patients treated with this combination. OUTLINE: This is a phase I, dose-escalation study of romidepsin and lenalidomide followed by a phase II study. Patients receive rituximab intravenously (IV) over 90 minutes on day 1; romidepsin IV over 4 hours on either day 1, days 1 and 8, or days 1, 8, and 15; and lenalidomide orally (PO) on days 1-21. 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 every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
MTD, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I)
Time frame: 28 days
Overall response rate (Phase II)
A success is defined as a CR or partial response (PR) noted as the objective status. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.
Time frame: Up to 5 years
Adverse events profile, graded according to the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Time frame: Up to 30 days post-treatment
Toxicity profile, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment (Phase I)
Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Time frame: Up to 30 days post-treatment
Response profile, defined to be a CR or PR noted as the objective status (Phase I)
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population.
Time frame: Up to 5 years
CR rate (Phase II)
Will be estimated by the number of patients who achieve a CR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete response rate will be calculated.
Time frame: Up to 5 years
Survival time (Phase II)
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to death due to any cause, assessed up to 5 years
PFS (Phase II)
The distribution of PFS will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years
Incidence of adverse events, graded according to the revised NCI CTCAE version 4.0 (Phase II)
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Time frame: Up to 30 days post-treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.