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Mature B-Cell Lymphoma And Leukemia Study III

Primary Purpose

Mature B-Cell Lymphoma

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

COPAD

COP, COPD M3, CYM

COP, COPADM8, CYVE

About this trial

This is an interventional treatment trial for Mature B-Cell Lymphoma focused on measuring Lymphoma, Leukemia, Non-Hodgkin's Lymphoma

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
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.
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:

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.

Sites / Locations

Rady Children's Hospital San Diego
St. Jude Children's Research Hospital
Children's Cancer Hospital
National University Health System

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Arm Label

Group A

Group B

Group C

Arm Description

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

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.

Any CNS involvement and/or bone marrow involvement ≥ 25% blasts. For CNS involvement one or more of the following applies: Any L3 blasts in CSF Cranial nerve palsy (if not explained by extracranial tumor) Clinical spinal cord compression Isolated intracerebral mass 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

Outcomes

Primary Outcome Measures

Gene differential profiling of Burkitt Lymphoma (BL) vs. non-BL

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.

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.

Integrated analysis of CNVs and gene expressions

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.

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.

Pattern of EBV protein expression (e.g., EBNA 3) in EBV-positive lymphomas and to compare patterns of EBV protein expression with clinical, laboratory and outcome data

Point estimates and 95% CIs of the frequency of EBV-positive BL will be calculated for each geographical region. EBV protein expression will be described by summary statistics. Relationship of EBV protein expression with clinical, laboratory, and outcome features will be explored using appropriate statistical methods such as general linear models.

Secondary Outcome Measures

Complete response rate

Complete response rate will be estimated with exact 95% CI based on the binomial distribution, and it will be reported as the percentage of patients who reached complete remission among eligible patients treated at SJCRH

Event-free survival

Event-free survival (EFS) will be estimated among eligible patients treated at SJCRH by the Kaplan-Meier estimator. The events will include: (1) death while in continuous CR, (2) relapse, (3) secondary malignancy, and (4) failure to achieve complete response (CR).

Overall Survival

Overall survival (OS) will be estimated among eligible patients treated at SJCRH by the Kaplan-Meier estimator.

Percentage of participants who complete therapy with the use of rituximab

Percentages of possible rituximab-related toxicities will be described in terms of the estimates of the number of episodes and the cumulative incidence throughout the treatment period for each type of toxicity.

Number of possible rituximab-related toxicities

The number of episodes and the cumulative incidence throughout the treatment period for each type of possible rituximab-related toxicity will be estimated and reported.

Full Information

NCT ID

NCT01046825

First Posted

January 8, 2010

Last Updated

September 11, 2023

Sponsor

St. Jude Children's Research Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01046825

Brief Title

Mature B-Cell Lymphoma And Leukemia Study III

Official Title

Mature B-Cell Lymphoma And Leukemia Study III

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 9, 2010 (Actual)

Primary Completion Date

August 31, 2023 (Actual)

Study Completion Date

August 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

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. 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. 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. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mature B-Cell Lymphoma

Keywords

Lymphoma, Leukemia, Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

128 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A

Arm Type

Other

Arm Description

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

Arm Title

Group B

Arm Type

Other

Arm Description

Arm Title

Group C

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

COPAD

Other Intervention Name(s)

VCR, prednisone, Adriamycin, cytoxan, filgrastim, Neupogen, Neulasta®

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

COP, COPD M3, CYM

Other Intervention Name(s)

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

Intervention Description

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

Intervention Name(s)

COP, COPADM8, CYVE

Other Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

Gene differential profiling of Burkitt Lymphoma (BL) vs. non-BL

Description

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 last participant is enrolled

Title

Catalog and estimate frequencies of copy number variations in childhood lymphomas

Description

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.

Time Frame

1 year after the last participant is enrolled

Title

Integrated analysis of CNVs and gene expressions

Description

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.

Time Frame

1 year after the last participant is enrolled

Title

Pattern and frequency of XLP gene mutations presenting with B-cell lymphomas in the United States and selected geographic regions

Description

Time Frame

1 year after the last participant enrollment

Title

Pattern of EBV protein expression (e.g., EBNA 3) in EBV-positive lymphomas and to compare patterns of EBV protein expression with clinical, laboratory and outcome data

Description

Time Frame

1 year after the last participant is enrolled

Secondary Outcome Measure Information:

Title

Complete response rate

Description

Time Frame

5 years after completion of therapy

Title

Event-free survival

Description

Time Frame

5 years after completion of therapy

Title

Overall Survival

Description

Overall survival (OS) will be estimated among eligible patients treated at SJCRH by the Kaplan-Meier estimator.

Time Frame

5 years after completion of therapy

Title

Percentage of participants who complete therapy with the use of rituximab

Description

Time Frame

at the end of therapy (maximum of 9 months after enrollment)

Title

Number of possible rituximab-related toxicities

Description

The number of episodes and the cumulative incidence throughout the treatment period for each type of possible rituximab-related toxicity will be estimated and reported.

Time Frame

at the end of therapy (up to 9 months after enrollment

10. Eligibility

Sex

All

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. 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: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raul Ribeiro, MD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rady Children's Hospital San Diego

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

Facility Name

Children's Cancer Hospital

City

Cairo

ZIP/Postal Code

11787

Country

Egypt

Facility Name

National University Health System

City

Singapore

ZIP/Postal Code

119228

Country

Singapore

12. IPD Sharing Statement

Links:

URL

http://www.stjude.org

Description

St. Jude Children's Research Hospital

URL

http://www.stjude.org/protocols

Description

Clinical Trials Open at St. Jude

Learn more about this trial

Mature B-Cell Lymphoma And Leukemia Study III

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