Treatment of Mature B-cell Lymphoma/Leukaemia

NCT ID: NCT00162656

Last Updated: 2012-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 848 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-05-31
• Study Completion Date: 2011-05-31

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

Conditions

B-Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard LMB B

Group Type: ACTIVE_COMPARATOR

LMB B

Intervention Type: DRUG

LMB B without COPADM3

Group Type: EXPERIMENTAL

without COPADM3

Intervention Type: DRUG

LMB B with half cyclophosphamide

Group Type: EXPERIMENTAL

half cyclophosphamide

Intervention Type: DRUG

LMB B without COPADM3 and with half cyclophosphamide

Group Type: EXPERIMENTAL

half cyclophosphamide

Intervention Type: DRUG

without COPADM3

Intervention Type: DRUG

LMB C standard

Group Type: ACTIVE_COMPARATOR

LMB C

Intervention Type: DRUG

LMB C with mini CYVE and without 3 maintenance courses

Group Type: EXPERIMENTAL

mini CYVE, without 3 maintenance courses

Intervention Type: DRUG

Interventions

half cyclophosphamide

Intervention Type: DRUG

without COPADM3

Intervention Type: DRUG

mini CYVE, without 3 maintenance courses

Intervention Type: DRUG

LMB B

Intervention Type: DRUG

LMB C

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Catherine Patte, MD

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Mitchell S Cairo, MD

Role: PRINCIPAL_INVESTIGATOR

Morgan Stanley Childrens Hospital of New York Presbyterian, Columbia University

Mary Gerrard, MD

Role: PRINCIPAL_INVESTIGATOR

Sheffield Children's Hospital

Locations

Morgan Stanley Childrens Hospital of New York Presbyterian

New York, New York, United States

Institut Gustave Roussy

Villejuif, , France

Sheffield Children's Hospital

Sheffield, , United Kingdom

Countries

United States; France; United Kingdom

References

Frazer JK, Li KJ, Galardy PJ, Perkins SL, Auperin A, Anderson JR, Pinkerton R, Buxton A, Gross TG, Michon J, Leverger G, Weinstein HJ, Harrison L, Shiramizu B, Barth MJ, Goldman SC, Patte C, Cairo MS. Excellent outcomes in children and adolescents with CNS+ Burkitt lymphoma or other mature B-NHL using only intrathecal and systemic chemoimmunotherapy: results from FAB/LMB96 and COG ANHL01P1. Br J Haematol. 2019 Apr;185(2):374-377. doi: 10.1111/bjh.15520. Epub 2018 Aug 16. No abstract available.

Reference Type: DERIVED

PMID: 30117142 (View on PubMed)

Other Identifiers

FAB LMB96

Identifier Type: -

Identifier Source: org_study_id