A Study of MabThera (Rituximab) Addition to Regularly Prescribed Chemotherapy in Patients With Untreated Mantle Cell Lymphoma.

Study Overview
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Brief Summary
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This multicenter, open-label study will assess the efficacy and safety of MabThera (rituximab) added to standard chemotherapy in participants with untreated Mantle Cell Lymphoma not eligible for autologous stem cell transplantation. Participants will receive MabThera (372 mg/m^2 intravenously) on Day 1 of each 28-day treatment cycle in addition to standard chemotherapy for 6 cycles. In participants experiencing complete or partial response, MabThera will be continued as consolidation therapy for 2 more cycles.

Official Title
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A Phase II Multicenter Open-label Study of MabThera(Rituximab) Addition to Regularly Prescribed Chemotherapy in Patients With Untreated Mantle Cell Lymphoma

Conditions
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Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Mitoxantrone
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult participants, >/=18 years of age untreated Mantle Cell Lymphoma, not eligible for Autologous Stem Cell Transplantation known mantle cell lymphoma international prognostic index (MIPI) at diagnosis Eastern Cooperative Oncology Group (ECOG) performance status 0-2 adequate hematological, renal and hepatic function Exclusion Criteria: known hypersensitivity to murine proteins or chemotherapy regimen previous first-line therapy history of other malignancy within the last 5 years, except for squamous cell carcinoma, basal cell carcinoma of the skin or in situ cervical carcinoma active infection clinically significant cardiac disease regular corticosteroid treatment in the 4 weeks prior to first dose of study drug

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>Rituximab, 375 milligram per meter square (mg/m^2) was given intravenously on Day 1 and then every 28 days (+/-7 days) for 6 cycles, followed by 2 consolidated infusions in responders as rituximab induction therapy. Rituximab infusions were administered concomitantly with prescribed chemotherapy i.e., fludarabine, cyclophosphamide and mitoxantrone (maximum 6 cycles). | Drug: Cyclophosphamide<br>* as prescribed, 6 cycles<br>Drug: Fludarabine<br>* as prescribed, 6 cycles<br>Drug: Mitoxantrone<br>* as prescribed, 6 cycles<br>Drug: Rituximab<br>* 375 mg/m^2 intravenously, Day 1 of each 28-day cycle, up to 8 cycles<br>* Other names: Mabthera/Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall Response Rate (ORR) was determined by tumor response according to International Workshop Group to Standardize Response Criteria for mantle cell lymphoma (MCL) criteria from confirmed evaluations of both target, radiographically evaluated, and non-target lesions. A responder is defined as a subject experiencing either a complete (CR)/ unconfirmed complete (Cru), or partial response (PR) by these criteria. As per criteria; CR = disappearance of all evidence of disease; CRu = the sum of the product of the diameters (SPD) of multiple nodes decreased by at least 75%; PR = regression of measurable disease and no new sites. | Up to 50 months (approximately) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival is defined as time from date of enrollment to the date of death, regardless of the cause of death. | From the time of enrollment until death due to any cause (up to 50 months [approximately]) | 
| Progression-free Survival (PFS) | PFS is defined as the interval between the day of enrollment and the first documentation of progressive disease or death. Progression of disease is defined as at least a 20 percent (%) increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. | From the time of enrollment until death due to any cause (up to 50 months [approximately]) | 
| Number of Participant With Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with study treatment. | Up to 50 months (approximately) |