Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma
|ClinicalTrials.gov Identifier: NCT02281279|
Recruitment Status : Withdrawn
First Posted : November 3, 2014
Last Update Posted : August 11, 2016
|Condition or disease||Intervention/treatment||Phase|
|B-cell Adult Acute Lymphoblastic Leukemia Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory Hairy Cell Leukemia Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Testicular Lymphoma Waldenström Macroglobulinemia||Biological: rituximab Drug: lenalidomide Drug: romidepsin Other: laboratory biomarker analysis||Phase 1 Phase 2|
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)
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.
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 (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Romidepsin, Rituximab and Lenalidomide (R3) in Relapsed/Refractory B Cell Lymphomas Including Transformed Follicular Lymphoma|
|Study Start Date :||October 2016|
|Estimated Primary Completion Date :||October 2020|
Experimental: Treatment (rituximab, romidepsin, lenalidomide)
Patients receive rituximab 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 PO on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: lenalidomide
Other Names:Drug: romidepsin
Other Names:Other: laboratory biomarker analysis
- 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) [ Time Frame: Up to 5 years ]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.
- Adverse events profile, graded according to the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) [ Time Frame: Up to 30 days post-treatment ]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.
- Toxicity profile, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment (Phase I) [ Time Frame: Up to 30 days post-treatment ]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.
- Response profile, defined to be a CR or PR noted as the objective status (Phase I) [ Time Frame: Up to 5 years ]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.
- CR rate (Phase II) [ Time Frame: Up to 5 years ]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.
- Survival time (Phase II) [ Time Frame: Time from registration to death due to any cause, assessed up to 5 years ]The distribution of survival time will be estimated using the method of Kaplan-Meier.
- PFS (Phase II) [ 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 ]The distribution of PFS will be estimated using the method of Kaplan-Meier.
- Incidence of adverse events, graded according to the revised NCI CTCAE version 4.0 (Phase II) [ Time Frame: Up to 30 days post-treatment ]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.
- BCL-2 sequence [ Time Frame: Baseline ]Will be assessed as mutation present vs. absent. The correlation between overall response (responder vs. non-responder) and mutation status will be evaluated using Fisher's exact test. The PFS in each group will be estimated using the Kaplan-Meier method. The differences in PFS between the two mutation groups will be assessed using the log-rank test.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02281279
|Principal Investigator:||Grzegorz Nowakowski||Mayo Clinic|