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. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
128
Vincristine Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.
GROUP B Treatment Details Intravenous fluids should be given at a rate of 3000 mL/m2/day. Use of rasburicase may preclude the need for HCO3 Pre-Phase: Cyclophosphamide, Vincristine, Prednis(ol)one, IT medications Induction (2 cycles): Vincristine, Prednis(ol)one, Methotrexate, Leucovorin, Cyclophosphamide, Doxorubicin, IT medications, G-CSF, Rituximab Consolidation (2 cycles): Methotrexate, Leucovorin, Cytarabine, IT medications, G-CSF, Rituximab In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.
Treatment: Intravenous fluids should be given at a rate of 3000 mL/m2/day. Use of rasburicase may preclude the need for HCO3. COP Pre-Phase: Cyclophosphamide, Vincristine, Prednis(ol)one, IT medications, Leucovorin. COPADM8 Induction (2 cycles): Vincristine, Prednis(ol)one, Methotrexate, Leucovorin, Cyclophosphamide, Doxorubicin, Rituximab, IT medications, G-CSF CYVE Consolidation (2 cycles): Cytarabine, High-Dose Ara-C, Etoposide, Rituximab, G-CSF. Maintenance No.1: Vincristine, Prednis(ol)one, Cyclophosphamide, Methotrexate, Leucovorin, Doxorubicin, IT medications, G-CSF. Maintenance No.2: Cytarabine, Etoposide, G-CSF, IT Medications. Maintenance No.3: Vincristine, Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF, IT Medications. Maintenance No. 4: Cytarabine, Etoposide, G-CSF, IT Medications. In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.
Rady Children's Hospital San Diego
San Diego, California, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Children's Cancer Hospital
Cairo, Egypt
National University Health System
Singapore, Singapore
Gene Differential Expression Profiling of Burkitt Lymphoma (BL) vs. Non-BL in the US and Other Selected Geographic Regions of the World
Gene expression levels in BL vs. non-BL will be analyzed through approximately 22,000 probesets on the Affymetrix U133A GeneChip by using two-factor analysis of variance model for each gene.
Time frame: 1 year after the participant is enrolled
Catalog and Estimate Frequencies of Copy Number Variations in Childhood Lymphomas
The prevalence of CNVs between different subtypes of childhood lymphomas and geographic regions will be reported and compared with exact chi-square or Fisher's test. The CNVs are derived from Affymetrix SNP arrays.
Time frame: 1 year after the participant is enrolled
Integrated Analysis of CNVs and Gene Expressions in the US and Other Selected Geographic Regions of the World
The association between the identified CNVs and gene expressions in the study cohort will be examined by using general linear models, and multiple tests will be considered. Gene expressions are measured by Affymetrix U133A arrays and CNVs are derived from Affymetrix SNP arrays.
Time frame: 1 year after the participant is enrolled
Pattern and Frequency of XLP Gene Mutations Presenting With B-cell Lymphomas in the United States and Selected Geographic Regions
Frequency of XLP mutation among boys will be calculated in each geographical region as well as in all regions pooled. The frequency is reported here as the number of boys with XLP gene mutations found in B-cell lymphomas boys.
Time frame: 1 year after the participant enrollment
Frequency of EBV Protein Expression (e.g., EBNA 3) in EBV-positive Lymphomas
Frequency of EBV-positive BL will be calculated for each geographical region.
Time frame: 1 year after the participant is enrolled
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