Clinical trial NCT01046825: Mature B-Cell Lymphoma And Leukemia Study III
Official title: Mature B-Cell Lymphoma And Leukemia Study III
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Mature B-Cell Lymphoma
Keywords: Lymphoma
Leukemia
Non-Hodgkin's Lymphoma
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2010-01-12
Enrollment: 128
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Exploratory Aims:

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Gene Differential Expression Profiling of Burkitt Lymphoma (BL) vs. Non-BL in the US and Other Selected Geographic Regions of the World
timeFrame: 1 year after the participant is enrolled
measure: Catalog and Estimate Frequencies of Copy Number Variations in Childhood Lymphomas
timeFrame: 1 year after the participant is enrolled
measure: Integrated Analysis of CNVs and Gene Expressions in the US and Other Selected Geographic Regions of the World
timeFrame: 1 year after the participant is enrolled
measure: Pattern and Frequency of XLP Gene Mutations Presenting With B-cell Lymphomas in the United States and Selected Geographic Regions
timeFrame: 1 year after the participant enrollment
measure: Frequency of EBV Protein Expression (e.g., EBNA 3) in EBV-positive Lymphomas
timeFrame: 1 year after the participant is enrolled
Secondary outcomes:
Other outcomes:
measure: Overall Survival
timeFrame: Up to 5 years after completion of therapy
measure: Event-free Survival
timeFrame: Up to 5 years after completion of therapy
measure: Complete Response Rate
timeFrame: Up to 5 years after completion of therapy
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Cairo
country: Egypt
facility: Children's Cancer Hospital
city: Singapore
country: Singapore
facility: National University Health System
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Raul Ribeiro, MD
role: PRINCIPAL_INVESTIGATOR
References: