A Study of MabThera (Rituximab) in Elderly Patients With Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of brief induction therapy with a chemotherapeutic regimen containing MabThera, followed by either maintenance therapy with MabThera or no further therapy. The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.

Official Title
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A Randomized, Open-label Study of MabThera Maintenance Therapy Compared With no Further Therapy After a Brief Induction With Chemotherapy Plus MabThera on Failure-free Survival in Treatment-naïve Elderly Patients With Advanced Follicular Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: rituximab [Mabthera/Rituxan]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients 60-75 years of age; B-cell follicular NHL; no previous treatment; active disease, with rapid progression. Exclusion Criteria: other cancer within 3 years of study, except carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ of the breast treated with lumpectomy; long-term use (>1 month) of systemic corticosteroids; central nervous system involvement; history of significant cardiovascular disease; positive test result for HIV, or hepatitis B or C.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: rituximab [Mabthera/Rituxan]<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression or Death | PFS from randomization was measured from the date of randomization to the date of documented disease progression, relapse, or death from any cause. PFS function was estimated using Kaplan-Meier product-limit method. Responding participants and participants who were lost to follow up were censored at their last assessment date. | 12, 24, and 34 months | 
| PFS Randomization- Percentage of Participants Estimated to be Free of Progression at 12, 24, and 34 Months | PFS from randomization was measured from the date of randomization to the date of documented disease progression, relapse, or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last assessment date. PFS was estimated using Kaplan-Meier methods. | 12, 24, and 34 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Estimated to be Free of Progression at 12, 24, and 36 Months | PFS from enrollment was measured from the date of enrollment to the date of disease progression, relapse, or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last assessment date. Estimates of PFS function were made with the Kaplan-Meier product-limit method. | 12, 24, and 36 months | 
| Disease-Free Survival (DFS) From Randomization - Percentage of Participants Disease Free at 12, 24, and 36 Months | DFS was defined for all participants who achieved a complete response (CR) or unconfirmed CR (CRu) at Month 3 or later, after the completion of induction phase and was measured from the time of randomization to the date of relapse or death as a result of lymphoma or acute toxicity of treatment. Participants without relapse were censored at their last assessment date. Estimates of DFS were made using Kaplan-Meier product-limit method. | 12, 24, and 36 months | 
| Overall Survival (OS) From Randomization - Percentage of Participants Estimated to be Alive at 12, 24, and 34 Months | OS from randomization was defined as the date of randomization to the date of death from any cause. Participants still alive at the time of the final analysis were censored at the date of the last contact. Estimates of the OS function were made by the Kaplan-Meier product-limit method. | 12, 24, and 34 months | 
| Overall Survival (OS) From Randomization - Percentage of Participants With Death | OS from randomization was defined as the date of randomization to the date of death from any cause. Participants still alive at the time of the final analysis were censored at the date of the last contact. Estimates of the OS function were made by the Kaplan-Meier product-limit method. | 12, 24, and 34 months | 
| OS From Enrollment - Percentage of Participants Estimated to be Alive at 12, 24, and 36 Months | OS from enrollment was defined as the date of enrollment to the date of death from any cause. Participants still alive at the time of the final analysis were censored at the date of the last contact. Estimates of the OS function were made by the Kaplan-Meier product-limit method. | 12, 24, and 36 months | 
| Percentage of Participants With a Response During the Induction Phase | Participants without a response assessment (due to any reasons) were considered as non-responders. | Months 1 to 8 | 
| Percentage of Participants With a Molecular Response in the Induction Phase | Molecular responders were defined as the proportion of CR/CRu participants with a positive bcl-2/IgH (non-Hodgkin's Lymphoma [NHL] marker) at baseline, whose laboratory values were undetectable after treatment. | Months 5 and 8 | 
| Duration of Response Using a Traditional Approach - Percentage of Participants Estimated to Have a Sustained Response at 12, 24, and 34 Months | Duration of response (DOR) was defined for all participants who achieved a response (CR, CRu, and PR) at Month 3 or later, after the completion of induction phase and was measured from the date of randomization until the date of progression, relapse, or death as a result of follicular lymphoma (FL). Participants without relapse, progression, or death for causes other than FL were censored at their last assessment date. Analyses on this endpoint were performed with two different approaches. For the traditional approach, duration of response was estimated as the proportion of participants alive without progression or relapse of disease with the Kaplan-Meier method. | Months 12, 24, and 34 | 
| Duration of Response Using the Competing Risk Approach - Cumulative Percentage of Participants With Progression, Relapse or Death as a Result of FL at 12, 24, and 34 Months | DOR was defined for all participants who achieved a response (CR, CRu, and PR) at Month 3 or later, after the completion of induction phase and was measured from the date of randomization until the date of progression, relapse, or death as a result of FL. Participants without relapse, progression, or death for causes other than FL were censored at their last assessment date. Analyses on this endpoint were performed with two different approaches. For the competing risk approach, deaths for causes other than FL were considered as competing events. DOR was estimated with the cumulative incidence of progression, relapse, or death as a result of FL. | Months 12, 24, and 34 |