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Mature B-Cell Lymphoma And Leukemia Study III

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by St. Jude Children's Research Hospital
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01046825
First received: January 8, 2010
Last updated: May 19, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Mature B-Cell Lymphoma Drug: COPAD Drug: COP, COPD M3, CYM Drug: COP, COPADM8, CYVE Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Mature B-Cell Lymphoma And Leukemia Study III

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Gene differential profiling of Burkitts Lymphoma (BL) vs. non-BL [ Time Frame: 1 year after the last participant is enrolled ]
    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 [ Time Frame: 1 year after the last participant is enrolled ]
    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 [ Time Frame: 1 year after the last participant is enrolled ]
    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 [ Time Frame: 1 year after the last participant enrollment ]
    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 [ Time Frame: 1 year after the last participant is enrolled ]

    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 [ Time Frame: 5 years after completion of therapy ]
    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 [ Time Frame: 5 years after completion of therapy ]
    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 [ Time Frame: 5 years after completion of therapy ]
    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 [ Time Frame: at the end of therapy (maximum of 9 months after enrollment) ]
    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 [ Time Frame: at the end of therapy (up to 9 months after enrollment ]
    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.


Estimated Enrollment: 122
Actual Study Start Date: September 9, 2010
Estimated Study Completion Date: October 31, 2022
Estimated Primary Completion Date: October 31, 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Group A

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

Group A will include: COPAD x 2 cycles.

Drug: COPAD
Vincristine Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF
Other Names:
  • VCR
  • prednisone
  • Adriamycin
  • cytoxan
  • filgrastim
  • Neupogen
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.

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
Other Names:
  • Elitek
  • Cytoxan
  • VCR
  • prednisone
  • MTX
  • folinic acid
  • Adriamycin
  • filgrastim
  • Rituxan
  • Ara-C
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

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, IT medications, G-CSF CYVE Consolidation (2 cycles): Cytarabine, High-Dose Ara-C, Etoposide, 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.

Other Names:
  • Elitek
  • cytoxan
  • VCR
  • prednisone
  • folinic acid
  • Adriamycin
  • filgrastim
  • Ara-C
  • VP16
  • MTX

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.

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 Group B 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 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 but will NOT receive rituximab. This screening must be done for eligibility 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. 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.
  6. 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 no emergency radiation)
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01046825

Contacts
Contact: John T Sandlund, MD 1-866-278-5833 referralInfo@stjude.org

Locations
United States, California
Rady Children's Hospital San Diego Recruiting
San Diego, California, United States, 92123
Contact: Deborah Schiff, MD    858-966-5811    dschiff@rchsd.org   
Principal Investigator: Deborah Schiff, MD         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: John T Sandlund, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: John T Sandlund, MD         
Egypt
Children's Cancer Hospital Recruiting
Cairo, Egypt, 11787
Contact: Hany Abdel Rahman, MD         
Principal Investigator: Hany Abdel Rahman, MD         
Singapore
National University Health System Recruiting
Singapore, Singapore, 119228
Contact: Allen Yeoh, MD       allen_yeoh@nuhs.edu.sg   
Principal Investigator: Allen Yeoh, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: John T Sandlund, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01046825     History of Changes
Other Study ID Numbers: SJBC3
NCI-2011-01251 ( Registry Identifier: NCI Clinical Trial Registration Program )
Study First Received: January 8, 2010
Last Updated: May 19, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Jude Children's Research Hospital:
Lymphoma
Leukemia
Non-Hodgkin's Lymphoma

Additional relevant MeSH terms:
Lymphoma
Leukemia
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Prednisone
Liposomal doxorubicin
Doxorubicin
Cyclophosphamide
Cytarabine
Leucovorin
Levoleucovorin
Folic Acid
Rasburicase
Lenograstim
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antidotes
Protective Agents
Vitamin B Complex

ClinicalTrials.gov processed this record on June 23, 2017