Mature B-Cell Lymphoma And Leukemia Study III

NCT ID: NCT01046825

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-09
• Study Completion Date: 2027-08-31

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.

Conditions

Mature B-Cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A

Completely resected stage I or completely resected abdominal stage II lesions.

Group A will include: COPAD x 2 cycles.

Group Type: OTHER

COPAD

Intervention Type: DRUG

Vincristine Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF

In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.

Group B

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.

Group Type: OTHER

COP, COPD M3, CYM

Intervention Type: 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.

Group C

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

Group Type: OTHER

COP, COPADM8, CYVE

Intervention Type: 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.

Interventions

COPAD

Vincristine Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF

In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.

Intervention Type: DRUG

COP, COPD M3, CYM

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.

Intervention Type: DRUG

COP, COPADM8, CYVE

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.

Intervention Type: DRUG

Other Intervention Names

VCR; prednisone; Adriamycin; cytoxan; filgrastim; Neupogen; Neulasta®; Elitek; Cytoxan; VCR; prednisone; MTX; folinic acid; Adriamycin; filgrastim; Rituxan; Ara-C; Neulasta®; Elitek; cytoxan; VCR; prednisone; folinic acid; Adriamycin; filgrastim; Ara-C; VP16; MTX; Rituxan; Neulasta®

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.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raul Ribeiro, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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

Countries

United States; Egypt; Singapore

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2011-01251

Identifier Type: REGISTRY

Identifier Source: secondary_id

SJBC3

Identifier Type: -

Identifier Source: org_study_id