Treatment of Mature B-cell Lymphoma/Leukaemia

Phase 3

Completed

• Conditions: B-Cell Lymphoma
• Interventions: Drug: LMB B; Drug: without COPADM3; Drug: half cyclophosphamide; Drug: LMB C; Drug: mini CYVE, without 3 maintenance courses

• Registration Number: NCT00162656
• Lead Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Brief Summary

This is an international trial conducted by three cooperative groups: SFOP (France, Belgium, Netherlands), CCG (USA, Canada, Australia), and UKCCSG (UK and Ireland). Children with mature B-cell lymphoma/leukaemia are stratified into three different risk groups (A, B, C) and receive treatment of progressive intensity. Randomized trials in the 2 biggest groups (B and C) test whether "reduced" therapy is equivalent to standard intensive therapy (LMB-89 B and C) in terms of event free survival. The reason for the modification is to reduce the long term toxicity which includes cardiotoxicity, impaired fertility and secondary malignancy. In group B, the modifications of treatment consists of a reduction of cyclophosphamide in COPADM2 and/or the elimination of COPADM3. In group C, the modification consists in a reduction of the doses in the CYVE courses and the elimination of the last 3 courses of maintenance treatment

Detailed Description

Group B: Randomized trial with factorial design. The 4 treatment arms are standard LMB89 therapy B, reduction of cyclophosphamide (CPM) in COPADM2, deletion of COPADM3, both reduction and deletion. Randomization occurs following COPADM1 and is stratified for national group, histology (large cell; small non cleaved cell) and stage (Murphy I orII; Murphy III+LDH\<2N; Murphy III+LDH\>2N or Murphy IV).

The primary analysis questions are whether reducing CPM dose in COPADM2 results in a smaller long-term EFS whether omitting COPADM3 results in a smaller long-term EFS

Group C: Randomized trial. The 2 treatment arms are standard LMB89 therapy C versus reduction of CYVE + deletion of the last 3 maintenance courses. Randomization occurs following COPADM2 and is stratified for national group, histology (large cell; small non cleaved cell) and CNS disease.

The primary analysis question is whether reducing CYVE and omitting the last 3 maintenance courses result in a smaller long-term EFS than standard LMB 89 treatment C

Study Timeline

• Study Start: 1996-05
• Primary Completion: 2004-05
• Study First Submitted: 2005-09-07
• Study First Submitted QC: 2005-09-08
• Study First Posted: 2005-09-13
• Study Completion: 2011-05
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-27
• Last Update Posted: 2012-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 848

Inclusion Criteria

• Newly diagnosed B lineage non-Hodgkin's lymphoma with Revised European American Lymphoma (REAL) II 9 (diffuse large cell lymphoma), 10 (Burkitt's lymphoma), or 11 (high grade B cell lymphoma, Burkitt's like) or bone marrow > 5% L3 blasts.
• Pre treatment imaging studies adequate to document Murphy disease stage
• Group B and C patients are eligible for randomization (Therapy stratification by group : Group A=completely resected stage I or completely resected abdominal stage II lesions, Group B= All cases not eligible for Group A or Group C, Group C= Any CNS involvement and/or bone marrow involvement ³ 25% blasts)
• Patients should be available for a minimum follow up of 36 months
• Informed consent prior to study entry

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Exclusion Criteria

• Anaplastic large cell Ki 1 positive lymphomas
• Previous chemotherapy.
• Congenital immunodeficiency
• Prior organ transplantation
• Previous malignancy of any type
• Known HIV positivity

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard LMB B	LMB B	-
LMB B without COPADM3	without COPADM3	-
LMB B with half cyclophosphamide	half cyclophosphamide	-
LMB B without COPADM3 and with half cyclophosphamide	half cyclophosphamide	-
LMB B without COPADM3 and with half cyclophosphamide	without COPADM3	-
LMB C standard	LMB C	-
LMB C with mini CYVE and without 3 maintenance courses	mini CYVE, without 3 maintenance courses	-

Primary Outcome Measures

Name	Time	Method
Event free survival	3 years	Event free survival (event = progressive disease or relapse or second malignancy or death from any cause)

Secondary Outcome Measures

Name	Time	Method
Survival	3 years
long term toxicity	10 years	long term toxicity: cardiotoxicity, impaired fertility, secondary malignancy

Trial Locations

Locations (3)

Sheffield Children's Hospital; 🇬🇧 Sheffield, United Kingdom

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Morgan Stanley Childrens Hospital of New York Presbyterian; 🇺🇸 New York, New York, United States