Mature B-Cell Lymphoma And Leukemia Study III
Mature B-Cell Lymphoma And Leukemia Study III
This is a phase III clinical trial using risk-adapted therapy. Treatment outcomes for
 children with B-cell NHL are excellent. Further improvements in outcome will likely be
 achieved through more focused study of the biology of the tumors and prospective studies of
 the late effects of treatment. Toward this end, this study features a spectrum of prospective
 biologic and late effect studies performed in patients treated with a modified regimen
 derived from the very successful LMB-96 regimen.
1. This study will perform analysis of newly diagnosed mature B-cell lymphomas (e.g.
 Burkitt lymphoma/leukemia, DLBCL, and MLBCL) obtained from participants in different
 parts of the world.

 2. This study will describe the types and frequency of mutations in the ARF-HDM2-TP53
 pathway, in B-cell lymphomas in the United States and that found in selected geographic
 regions of the world.

 3. This study will describe the expression of ARF-HDM2-TP53 and PUMA-associated pathways in
 B-cell lymphomas in the United States and that found in B-cell lymphomas of other
 selected geographic regions of the world.

 4. This study will describe the pattern and frequency of XLP gene mutations presenting with
 B-cell lymphomas in the United States and selected geographic regions.

 5. This study will describe the frequency of EBV-positive B-cell lymphomas in the United
 States and selected geographic regions of the world: and will describe the pattern of
 EBV protein and gene expression (e.g., EBNA 3) in EBV-positive lymphomas and the study
 will compare patterns of EBV protein and gene expression with clinical, laboratory and
 outcome data.

 Secondary Objective:

 To estimate the complete response rate, event-free survival, and overall survival rates in
 patients with Burkitt lymphoma (BL), Burkitt leukemia/B-cell acute leukemia (B-ALL) and
 diffuse large B-cell lymphoma (DLBCL) treated with a stage-adapted regimen based on the St.
 Jude B-cell II protocol.
Inclusion Criteria:

 St. Jude participants and collaborating sites participating in therapeutic and biological
 objectives:

 1. Participant must have a histologic diagnosis of a mature B cell lymphoma (e.g.,
 Burkitt lymphoma/leukemia, atypical Burkitt lymphoma, diffuse large B-cell lymphoma,
 mediastinal large B-cell lymphoma, mature B-cell lymphoma NOS) as defined in the WHO
 classification.

 2. Participant must be previously untreated, (no more than 72 hours of steroids, one
 intrathecal chemotherapy treatment, and/or emergency radiation).

 3. Participant must be < 22 years of age at the time of diagnosis

 4. For selected higher-risk CD20+ Group B and all CD20+ Group C participants receiving
 rituximab only (e.g., those with MLBLC, Stage III with LDH ≥ 2 times upper limit of
 normal (ULN), and/or bone marrow/CNS involvement: All participants who will receive
 rituximab must have hepatitis screening prior to enrollment. Participants whose
 results indicate that they are carrier of hepatitis B can still be treated per Group B
 or C but will NOT receive rituximab. This screening must be done for eligibility for
 participants who will receive rituximab, BUT the results are not needed prior to
 enrollment:

 -  Hepatitis B immunization status (vaccination Yes or No)

 -  HBsAg

 -  Anti-HBs antibody

 -  Anti-HBc antibody.

 5. All participants must have screening prior to enrollment; participants whose results
 indicate that they are carrier of hepatitis B can still be treated per group B and C
 but will NOT receive rituximab

 6. HIV test has been obtained within 42 days. Participants who test positive for HIV
 cannot be enrolled on therapeutic part of study, but are still eligible for biology
 studies.

 7. Informed consent must be obtained according to St. Jude guidelines before enrollment
 into study.

 Participants from Collaborating Sites Participating in Biological Objectives Only:

 1. Participant must have a histologic diagnosis of a mature B cell lymphoma (e.g.,
 Burkitt lymphoma/leukemia, atypical Burkitt lymphoma, diffuse large B-cell lymphoma,
 mediastinal large B-cell lymphoma, mature B-cell lymphoma NOS) as defined in the WHO
 classification.

 2. Participant must be < 22 years of age at the time of diagnosis.

 3. Participant must be previously untreated (no more than 72 hours of steroids, one
 intrathecal chemotherapy treatment, and/or emergency radiation) at the time of the
 diagnostic biopsy.

 4. Informed consent must be obtained by local PI or his/her designee according to
 ICH/Good Clinical Practice and local guidelines before enrollment into study.

 Exclusion Criteria:

 Participants from Collaborating Sites Participating in Therapeutic and Biological
 Objectives:

 1. Participants known to be HIV positive (for therapeutic part of protocol, HIV
 participants are eligible for biology studies).

 2. Participants who are pregnant or lactating.

 3. Inability or unwillingness of research participant or legal guardian to consent.

 Participants from Collaborating Sites Participating in Biological Objectives Only:

 1. Inability or unwillingness of research participant or legal guardian to consent.

 2. Histologic diagnosis other than a mature B-cell lymphoma as defined in the WHO
 classification.