Mature B-Cell Lymphoma And Leukemia Study III

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 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: February 26, 2015
Last verified: February 2015
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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: 60
Study Start Date: January 2009
Estimated Study Completion Date: October 2022
Estimated Primary Completion Date: October 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 transcriptional profiling and genome-wide analysis of DNA copy number abnormalities and loss-of-heterozygosity using DNA microarrays in children with newly diagnosed diffuse large B-cell lymphomas (DLBCL) and small non-cleaved lymphomas from different parts of the world.
  2. This study will describe the types and frequency of mutations in the ARF-HDM2-TP53 pathway, in "non-endemic" B-cell lymphomas (United States) and those 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 (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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

St. Jude Participants:

  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 and/or emergency radiation)
  3. Participant must be < 22 years of age at the time of diagnosis
  4. For Group B participants with mediastinal large B cell lymphoma (MLBCL) disease only (receiving rituximab) - All participants with MLBCL assigned to Group B 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. 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 but will NOT receive rituximab.
  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. 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 with prior therapy (except steroids or RT)
  2. Participants known to be HIV positive (for therapeutic part of protocol, HIV participants are eligible for biology studies).
  3. Participants who are pregnant or lactating
  4. Inability or unwillingness of research participant or legal guardian to consent
  5. Participants who received emergent steroids and/or radiation prior to biopsy may be included in therapeutic part of study, but will be excluded from biology studies.

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
  3. Participants who received emergent steroids and/or radiation prior to biopsy
  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 Info@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    info@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:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01046825     History of Changes
Other Study ID Numbers: SJBC3
Study First Received: January 8, 2010
Last Updated: February 26, 2015
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Lymphoma, B-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Doxorubicin
Folic Acid
Lenograstim
Levoleucovorin
Liposomal doxorubicin
Prednisone
Adjuvants, Immunologic
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antidotes
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Glucocorticoids
Growth Substances
Hematinics
Hematologic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Micronutrients

ClinicalTrials.gov processed this record on March 26, 2015