A Study to Evaluate the Efficacy of Lenalidomide as Maintenance Therapy After Completion of First-line Combination Chemotherapy in Patients With Mantle Cell Lymphoma (MCL).

Study Overview
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Brief Summary
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A study to evaluate the efficacy of lenalidomide as maintenance therapy after completion of first-line combination chemotherapy in patients with mantle cell lymphoma (MCL) who are not candidates for transplantation and have achieved partial response (PR) or complete response (CR). This study was prematurely terminated by the sponsor in light of new unpublished data that rendered the current design of the study no longer clinically relevant. A study design with the control arm of no active treatment was no longer appropriate. The termination of the trial was not based on any safety concerns in the study.

Official Title
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A Phase 3 Multicenter, Randomized, Double-blind, Placebo-Controlled, First Line Maintenance Study Of Lenalidomide (Revlimid®) In Patients With Mantle-Cell Lymphoma

Conditions
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Mantle Cell Lymphoma, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Lenalidomide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-proven mantle cell non-Hodgkin's lymphoma, One of the following first-line induction chemotherapy regimens with rituximab: (1) combination regimen containing all of the following components: cyclophosphamide, vincristine, adriamycin and a glucocorticoid; (2) Fludarabine containing regimen such as FC (fludarabine, cyclophosphamide) Achieved a PR or better response after the first-line induction chemotherapy regimen (assessed by 2007 Revised Response Criteria for Malignant Lymphoma) ECOG performance status score of ≤ 2 Willing to follow pregnancy precaution Exclusion Criteria: Patients who have received more than 1 line of induction chemotherapy; Patients who have received less than 4 cycles of R-CHOP, R-CHOP-like, or R-FC are ineligible; Patients who achieved stable disease or progressive disease as best response with first line-induction chemotherapy; Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5*10^9/L) Platelet count < 60,000/mm^3 (60*10^9/L) Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT)) > 3.0 times upper limit of normal (ULN), except in patients with documented liver involvement by lymphoma Serum bilirubin > 1.5 times ULN, except in case of Gilbert's Syndrome and documented liver involvement by lymphoma Calculated creatinine clearance (i.e. Cockcroft-Gault formula) of < 30 mL /min Active or any history of central nervous system (CNS) lymphoma or leptomeningeal involvement by lymphoma Subjects at high risk for deep vein thrombosis (DVT) not willing to take DVT prophylaxis Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide<br>Lenalidomide - 15 mg orally once daily on Days 1-21 of every 28-day cycle for a maximum of 2 years or until disease progression, unacceptable toxicity develops or voluntary withdrawal. | Drug: Lenalidomide<br>* 15 mg orally once daily on Days 1-21 of every 28-day cycle for a maximum of 2 years or until disease progression, unacceptable toxicity develops or voluntary withdrawal.<br>* Other names: Revlimid;|
| Experimental: Placebo<br>Placebo (identical matched capsule) orally once daily on Days 1-21 of every 28-day cycle for a maximum of 2 years or until disease progression, unacceptable toxicity develops or voluntary withdrawal. | Other: Placebo<br>* Placebo (identical matched capsule) orally once daily on Days 1-21 of every 28-day cycle for a maximum of 2 years or until disease progression, unacceptable toxicity develops or voluntary withdrawal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as the time from randomization into the study to the first observation of disease progression or death due to any cause. Progression, as defined by the 2007 Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), is any new lesion or increase by 50% of previously involved sites from nadir. Study terminated prematurely. Analysis not conducted. | up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was defined as the time from randomization to death from any cause. Study terminated prematurely. Analysis not conducted. | up to 7 years | 
| Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with treatment-emergent adverse events (TEAEs) during the treatment period plus 30 days. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator. The National Cancer Institute (NCI)'s Common Toxicity Criteria for AEs (NCI CTC) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. | up to 9 months | 
| Time to Progression | Time to progression was defined as the time from the date of randomization until the first date of documented disease progression. Study terminated prematurely. Analysis not conducted. | up to 7 years | 
| Time to Treatment Failure | Time to treatment failure was defined as the time from randomization until the date at which a participant was removed from treatment due to progression, toxicity, refusal or death or received another Non-Hodgkin Lymphoma (NHL) therapy, whichever occurs first. | up to 2 years | 
| Participants With a Tumor Response | Number of participants with a measurable tumor at time of randomization who achieve a response. Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms if present before therapy. Partial response (PR) is defined as the regression of measurable disease and no appearance of new sites of disease. For full definitions, please refer to the 2007 Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Study terminated prematurely. Analysis not conducted. | up to 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mantle Cell Lymphoma, Non-Hodgkin's Lymphoma, CC-5013, Revlimid, Lenalidomide