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

Phase 2

Terminated

• Conditions: Diffuse Large B-Cell Lymphoma
• Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mitoxantrone; Drug: Rituximab

• Registration Number: NCT01144403
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-06-14
• Study First Submitted QC: 2010-06-14
• Study First Posted: 2010-06-15
• Primary Completion: 2014-08
• Study Completion: 2014-08
• Results First Submitted: 2016-06-20
• Status Verified: 2016-07
• Results First Submitted QC: 2016-07-18
• Results First Posted: 2016-08-29
• Last Update Submitted: 2016-08-31
• Last Update Posted: 2016-10-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rituximab	Mitoxantrone	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).
Rituximab	Cyclophosphamide	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).
Rituximab	Fludarabine	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).
Rituximab	Rituximab	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).

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to 50 months (approximately)	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From the time of enrollment until death due to any cause (up to 50 months [approximately])	Overall survival is defined as time from date of enrollment to the date of death, regardless of the cause of death.
Progression-free Survival (PFS)	From the time of enrollment until death due to any cause (up to 50 months [approximately])	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.
Number of Participant With Adverse Event (AE)	Up to 50 months (approximately)	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.