Clinical trial NCT00162656: Treatment of Mature B-cell Lymphoma/Leukaemia
Official title: Treatment of Mature B-cell Lymphoma/Leukaemia A SFOP LMB 96/CCG 5961/UKCCSG NHL 9600 Cooperative Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: B-Cell Lymphoma
Keywords: B-Cell Lymphoma
Lead sponsor: Gustave Roussy, Cancer Campus, Grand Paris
Sponsor class: OTHER
First posted: 2005-09-13
Enrollment: 848
Sex: ALL
Minimum age (years): 6
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Event free survival
timeFrame: 3 years
Secondary outcomes:
measure: Survival
timeFrame: 3 years
measure: long term toxicity
timeFrame: 10 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Morgan Stanley Childrens Hospital of New York Presbyterian
state: New York
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Catherine Patte, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Morgan Stanley Childrens Hospital of New York Presbyterian, Columbia University
name: Mitchell S Cairo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sheffield Children's Hospital
name: Mary Gerrard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.