Treatment of Mature B-cell Lymphoma/Leukaemia

Overview

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 Title of Study: “Treatment of Mature B-cell Lymphoma/Leukaemia A SFOP LMB 96/CCG 5961/UKCCSG NHL 9600 Cooperative Study”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: May 2004

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

Interventions

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

Arms, Groups and Cohorts

• Active Comparator: Standard LMB B
• Experimental: LMB B without COPADM3
• Experimental: LMB B with half cyclophosphamide
• Experimental: LMB B without COPADM3 and with half cyclophosphamide
• Active Comparator: LMB C standard
• Experimental: LMB C with mini CYVE and without 3 maintenance courses

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

• Survival
  • Time Frame: 3 years
• long term toxicity
  • Time Frame: 10 years
  • long term toxicity: cardiotoxicity, impaired fertility, secondary malignancy

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 6 Months

Maximum Age: 20 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Gustave Roussy, Cancer Campus, Grand Paris
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Catherine Patte, MD, Principal Investigator, Gustave Roussy, Cancer Campus, Grand Paris
  • Mitchell S Cairo, MD, Principal Investigator, Morgan Stanley Childrens Hospital of New York Presbyterian, Columbia University
  • Mary Gerrard, MD, Principal Investigator, Sheffield Children’s Hospital