Lenalidomide With or Without Rituximab After Standard Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma
RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether lenalidomide is more effective with or without rituximab in treating diffuse large B-cell non-Hodgkin lymphoma.
PURPOSE: This randomized phase II trial is studying lenalidomide to see how well it works when given with or without rituximab after standard chemotherapy in treating patients with diffuse large B-cell non-Hodgkin lymphoma.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab as Maintenance Therapy Following Standard Chemotherapy for Patients With High/High-intermediate Risk Diffuse Large B-Cell Lymphoma|
- Disease-free survival at 1 year [ Time Frame: From on-treatment date to disease recurrence up to 1 year ] [ Designated as safety issue: No ]Estimated probable duration of life from on‐study date to date of death from any cause, using the Kaplan‐Meier method where death is an event, with censoring for non‐expired patients at greater of off‐study date or last known alive.
- Disease-free survival at 2 years [ Time Frame: From on-treatment date to disease recurrence up to 2 years ] [ Designated as safety issue: No ]
Estimated probable duration of life from on‐study date to date of death from any cause, using the Kaplan‐Meier method where death is an event, with censoring for non‐expired patients at greater of off‐study date or last known alive.
- Number of patients with each worst‐grade toxicity [ Time Frame: 30 days after completing treatment ] [ Designated as safety issue: Yes ]Count of patients according to the worst‐grade toxicity experienced by each, where worst‐grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life‐threatening; grade 5, death.
- Investigate potential predictive biomarkers of clinical response or resistance to lenalidomide [ Designated as safety issue: No ]
- Concordance between IHC for GCB and non-GCB subtypes to the gene expression profiles associated with the subtypes [ Designated as safety issue: No ]
|Study Start Date:||October 2008|
|Estimated Study Completion Date:||July 2015|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
|Experimental: Arm I: Lenalidomide||
Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Other Name: Revlimid
Experimental: Arm II: Lenalidomide and Rituximab IV
Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity.
Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles
Other Name: RevlimidDrug: Rituximab
Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
Other Name: Rituxan
- To assess the 1-year disease-free and relapse-free survival of patients with high- or high/intermediate-risk diffuse large B-cell non-Hodgkin lymphoma treated with maintenance therapy comprising lenalidomide with or without rituximab following standard chemotherapy.
- To assess the 2-year disease-free survival of patients treated with these regimens.
- To define the safety and toxicity profile of these regimens.
- To perform antibody-dependent cellular cytotoxicity assays using peripheral blood mononuclear cell samples from these patients.
- To assess the change in the number of natural killer cells by flow cytometric analysis.
- To evaluate cytokines including, but not limited to, sIL-2R, IL-6, IL-15, IL-12, TNF-α, and IFN-γ in these patients.
- To study the KIR genotype receptor and FCγR polymorphisms.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity.
Peripheral blood mononuclear cells are collected periodically for correlative studies. Samples are analyzed for change in the number of natural killer cells by flow cytometry; antibody-dependent cellular cytotoxicity by assay; cytokines; KIR genotype receptor; and FCγR polymorphisms.
After completion of study therapy, patients are followed at 30 days and then every 3 months for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00765245
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599-7295|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Vanderbilt-Ingram Cancer Center - Cool Springs|
|Nashville, Tennessee, United States, 37064|
|Vanderbilt-Ingram Cancer Center at Franklin|
|Nashville, Tennessee, United States, 37064|
|Principal Investigator:||Nishitha Reddy, MD||Vanderbilt-Ingram Cancer Center|