Mature B-Cell Lymphoma And Leukemia Study III

NCT01046825 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: SJBC3NCI-2011-01251
• Study Type: interventional
• Target: 128
• Locations: 3 countries
• Sites: 4

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.

Conditions

Mature B-Cell Lymphoma

Keywords

Lymphoma; Leukemia; Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  1 year after the participant is enrolled

Other Outcomes (3)

• Overall Survival

  Up to 5 years after completion of therapy

• Event-free Survival

  Up to 5 years after completion of therapy

• Complete Response Rate

  Up to 5 years after completion of therapy

Study Arms (3)

Group A

OTHER

Completely resected stage I or completely resected abdominal stage II lesions. Group A will include: COPAD x 2 cycles.

Drug: COPAD

Group B

OTHER

All cases not eligible for Group A or Group C. (Murphy Stage III and non-CNS Stage IV) Group B will include the intervention COP, COPD M3, CYM as follows: Pre-Phase: COP Induction: COPAD M3 x 2 cycles Consolidation: CYM x 2 cycles.

Drug: COP, COPD M3, CYM

Group C

OTHER

Any CNS involvement and/or bone marrow involvement ≥ 25% blasts. For CNS involvement one or more of the following applies: 1. Any L3 blasts in CSF 2. Cranial nerve palsy (if not explained by extracranial tumor) 3. Clinical spinal cord compression 4. Isolated intracerebral mass 5. Parameningeal extension: cranial and/or spinal Group C will include the intervention COP, COPADM8, CYVE as follows: Pre-Phase: COP Induction: COPADM8 cycle 1 Induction: COPADM8 Cycle 2 Consolidation: CYVE x 2 cycles and Maintenance

Drug: COP, COPADM8, CYVE

Interventions

COPAD DRUG

Vincristine Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.

Also known as: VCR, prednisone, Adriamycin, cytoxan, filgrastim, Neupogen, Neulasta®

Group A

COP, COPADM8, CYVE DRUG

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.

Also known as: Elitek, cytoxan, VCR, prednisone, folinic acid, Adriamycin, filgrastim, Ara-C, VP16, MTX, Rituxan, Neulasta®

Group C

COP, COPD M3, CYM DRUG

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.

Also known as: Elitek, Cytoxan, VCR, prednisone, MTX, folinic acid, Adriamycin, filgrastim, Rituxan, Ara-C, Neulasta®

Group B

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• St. Jude participants and collaborating sites participating in therapeutic and biological objectives:
• 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.
• Participant must be previously untreated, (no more than 72 hours of steroids, one intrathecal chemotherapy treatment, and/or emergency radiation).
• Participant must be \< 22 years of age at the time of diagnosis
• 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.
• 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
• 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.
• Informed consent must be obtained according to St. Jude guidelines before enrollment into study.
• Participants from Collaborating Sites Participating in Biological Objectives Only:
• 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.
• Participant must be \< 22 years of age at the time of diagnosis.

You may not qualify if:

• Participants from Collaborating Sites Participating in Therapeutic and Biological Objectives:
• Participants known to be HIV positive (for therapeutic part of protocol, HIV participants are eligible for biology studies).
• Participants who are pregnant or lactating.
• Inability or unwillingness of research participant or legal guardian to consent.
• Participants from Collaborating Sites Participating in Biological Objectives Only:
• Inability or unwillingness of research participant or legal guardian to consent.
• Histologic diagnosis other than a mature B-cell lymphoma as defined in the WHO classification.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (4)

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Children's Cancer Hospital

Cairo, 11787, Egypt

Location

National University Health System

Singapore, 119228, Singapore

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Lymphoma; Leukemia; Lymphoma, Non-Hodgkin

Interventions

Prednisone; Doxorubicin; Cyclophosphamide; Filgrastim; pegfilgrastim; rasburicase; Leucovorin; Rituximab; Cytarabine; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Results Point of Contact

• Title: Raul Ribeiro, MD
• Organization: St. Jude Children's Research Hospital

raul.ribeiro@stjude.org

901-595-3694

Study Officials

• Raul Ribeiro, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2010
• First Posted: January 12, 2010
• Study Start: September 9, 2010
• Primary Completion: August 31, 2023
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 10, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-12

Locations

EG (1); SG (1); US (2)