SJBC3: Mature B-cell Lymphoma and Leukemia Study III

Risk-Adapted Therapy in Treating Young Patients with Mature B-Cell Lymphoma or Leukemia

Category:

Leukemia / Lymphoma

Diseases Treated:

Leukemia and lymphoma

Eligibility Overview:

  • 21 years of age or younger
  • Newly diagnosed mature B-cell non-Hodgkin lymphoma and leukemia
  • Has not been previously treated
  1. 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.

    Primary Objectives

    1. 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. 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. 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. Describe the pattern and frequency of XLP gene mutations presenting with B-cell lymphomas in the United States and selected geographic regions
    5. 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 (eg, EBNA 3) in EBV-positive lymphomas and the study will compare patterns of EBV protein and gene expression with clinical, laboratory and outcome data

    Study Arms

    Group A

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

    Intervention:

    Drugs: COPAD x 2 cycles- Vincristine Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF

    Group B

    All cases not eligible for Group A or Group C. (Murphy Stage III and non-CNS Stage IV)

    Intervention:

    Drugs: COP, COPD M3, CYM

    • 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

    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

    Intervention

    Drugs: COP, COPADM8, CYVE

    • Pre-Phase: Cyclophosphamide, Vincristine, Prednis(ol)one, IT medications, Leucovorin
    • 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

    Eligibility Criteria

    Inclusion Criteria:

    St. Jude Participants:

    • Participant must have a histologic diagnosis of a mature B-cell lymphoma (eg, 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 and/or emergency radiation)
    • Participant must be <22 years of age at the time of diagnosis
    • Participants with mediastinal large B-cell lymphoma (MLBCL) disease only
      • All participants with MLBCL must have hepatitis screening prior to enrollment
        • Participants whose results indicate that they are carrier of hepatitis B can still be treated
        • 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
    • 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)

    Participants from Collaborating Sites Participating in Biological Objectives Only:

    • Participant must have a histologic diagnosis of a mature B cell lymphoma (eg,  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

    Exclusion Criteria:

    Participants from Collaborating Sites Participating in Therapeutic and Biological Objectives:

    • Participants with prior therapy (except steroids or RT)
    • Participants known to be HIV positive (for therapeutic part of protocol, HIV participants are eligible for biology studies)
    • Participants who are pregnant or lactating
    • 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:

    • Histologic diagnosis other than a mature B-cell lymphoma as defined in the WHO classification
    • Participants who received emergent steroids and/or radiation prior to biopsy

    Study Design

    • Allocation: Non-Randomized
    • Endpoint Classification: Safety/Efficacy Study
    • Intervention Model: Parallel Assignment
    • Masking: Open Label
    • Primary Purpose: Treatment
  2. About this clinical trial

    SJBC3 is a Phase III clinical trial aimed at preventing your child’s newly diagnosed mature B-cell non-Hodgkin lymphoma and leukemia from coming back after treatment. Mature B-cell non-Hodgkin lymphomas are fast-growing cancers; however, they are also one of the most treatable and curable childhood cancers.

    Effective treatment, resulting in long-term remission (no sign and symptoms of disease), occurs when patients are treated with several strong chemotherapy drugs. Although most patients are cured from their cancer, some may experience serious side effects from treatment later in life. In this trial, St. Jude researchers will look at developing better treatments while trying to reduce some of the possible long-term side effects that are common with strong chemotherapy drugs.

    Purpose of this clinical trial

    This study has two parts—treatment and biology. In the biology part, researchers will study the normal and cancerous blood and tissue samples from participants in the U.S. and around the world. Researchers will study differences between the samples to learn more about:

    • How changes in normal cells lead to mature B-cell non-Hodgkin lymphoma in children
    • How well a person’s disease will respond to medicine and what medicines may work best

    In the treatment part, St. Jude researchers will study the long-term side effects of treatment in participants from St. Jude and Rady Children’s Hospital, San Diego. Researchers will use what they learn to help develop more comprehensive plans for managing and/or preventing late effects of therapy.  

    Treatment

    Your child’s specific mature B-cell non-Hodgkin lymphoma diagnosis will determine the treatment plan that will be used. First, all participants will receive several tests to find out where cancer cells are in the body (cancer staging). Your child will be placed into one of three groups based on whether your child’s cancer has a high, standard or low risk of coming back after treatment. Participants in all of the treatment groups will be given combination chemotherapy (multiple cancer drugs). The intensity of the three groups varies by drugs used, drug dosage and duration of therapy.

    Participants who have a type of B-cell lymphoma called mediastinal large B-cell lymphoma will receive an antibody called rituximab, in addition to combination chemotherapy. An antibody is a man-made version of immune system proteins that finds and attaches to the surface of cancer cells without harming healthy cells.

    Rituximab has been given safely along with standard chemotherapy drugs to adults and some children with non-Hodgkin lymphoma. However, rituximab given with standard chemotherapy to treat children with lymphoma, as will be one on this study, is not yet considered standard treatment.

    Eligibility overview

    • 21 years of age or younger
    • Newly diagnosed mature B-cell non-Hodgkin lymphoma and leukemia
    • Has not been previously treated
  3. SJBC3  Quick View
    Sponsor St. Jude Children's Research Hospital
    Collaborator Children's Cancer Hospital Egypt
    Clinicaltrials.gov identifier NCT01046825
    Trial start date 2009
    Estimated enrollment 60
    Study type Interventional
    Study phases Phase 2
    Phase 3
    Conditions

    Mature B-cell lymphoma and leukemia

    Principal investigator John S. Sandlund, MD
    Ages Up to 21 years
    Study sites St. Jude Children’s Research Hospital and collaborating sites in the U.S., Egypt and Singapore
    For a consultation or to discuss SJBC3 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

John T. Sandlund, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.