Treatment of Mature B-cell Lymphoma/Leukaemia

Gustave Roussy

Status and phase: Completed; Phase 3

Conditions: B-Cell Lymphoma

Treatments: Drug: mini CYVE, without 3 maintenance courses; Drug: without COPADM3; Drug: LMB C; Drug: half cyclophosphamide; Drug: LMB B

Study type: Interventional

Funder types: Other

Identifiers

NCT00162656

FAB LMB96

Details and patient eligibility

About

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

Full 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

Enrollment: 848 patients

Sex: All

Ages: 6 months to 20 years old

Volunteers: No Healthy Volunteers

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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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848 participants in 6 patient groups

Standard LMB B

Active Comparator group

Treatment:

Drug: LMB B

LMB B without COPADM3

Experimental group

Treatment:

Drug: without COPADM3

LMB B with half cyclophosphamide

Experimental group

Treatment:

Drug: half cyclophosphamide

LMB B without COPADM3 and with half cyclophosphamide

Experimental group

Treatment:

Drug: half cyclophosphamide

Drug: without COPADM3

LMB C standard

Active Comparator group

Treatment:

Drug: LMB C

LMB C with mini CYVE and without 3 maintenance courses

Experimental group

Treatment:

Drug: mini CYVE, without 3 maintenance courses