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Rituximab, Rasburicase, and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Advanced B-Cell Leukemia or Lymphoma

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00057811
First received: April 7, 2003
Last updated: September 10, 2014
Last verified: September 2014
History of Changes
  Purpose
Phase II trial to study the effectiveness of combining rituximab and rasburicase with combination chemotherapy in treating young patients who have newly diagnosed advanced B-cell leukemia or lymphoma. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug with rituximab may kill more cancer cells. Chemoprotective drugs such as rasburicase may protect kidney cells from the side effects of chemotherapy.

Condition Intervention Phase
Childhood Burkitt Lymphoma
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Stage I Childhood Large Cell Lymphoma
Stage I Childhood Small Noncleaved Cell Lymphoma
Stage II Childhood Large Cell Lymphoma
Stage II Childhood Small Noncleaved Cell Lymphoma
Stage III Childhood Large Cell Lymphoma
Stage III Childhood Small Noncleaved Cell Lymphoma
Stage IV Childhood Large Cell Lymphoma
Stage IV Childhood Small Noncleaved Cell Lymphoma
Untreated Childhood Acute Lymphoblastic Leukemia
 Drug: doxorubicin hydrochloride
Drug: cyclophosphamide
Drug: methotrexate
Drug: rasburicase
Drug: leucovorin calcium
Drug: prednisone
Drug: methylprednisolone
Biological: filgrastim
Biological: rituximab
Drug: cytarabine
Drug: etoposide
Drug: vincristine sulfate
Drug: hydrocortisone sodium succinate
Other: laboratory biomarker analysis
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study To Determine The Toxicity Of The Addition Of Rituximab To The Induction And Consolidation Phases And The Addition Of Rasburicase To The Reduction Phase In Children With Newly Diagnosed Advanced B-Cell Leukemia/Lymphoma Treated With LMB/FAB Therapy

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Grade ≥ 3 Stomatitis [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    The incidence of grade ≥ 3 stomatitis. Grade 3 stomatitis: Confluent ulcerations or pseudomembranes; bleeding with minor trauma. Grade 4 stomatitis: Tissue necrosis; Significant spontaneous bleeding; life-threatening consequences

  • Response Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Response includes both complete and partial responses. Per protocol, complete Response is defined as the complete disappearance of all clinical evidence of disease by physical examination, by imaging studies, by bone marrow biopsy (where indicated), by CNS evaluation (where indicated) and by biopsy where there is a residual abnormality on an imaging study. Bone marrow must contain <5% blasts. CSF WBC must be <5/μL with no blasts or lymphomatous cells present. Partial response is defined as: at least a 50% reduction in the size of all measurable tumor areas. Each site is to be defined by the product of the maximum length, width and depth (3 dimensions). No lesion may progress. No new lesion may appear. Bone marrow must contain <5% blasts. CSF WBC must be <5/μL with no blasts or lymphomatous cells present..

  • Minimal Residual Disease [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
    The presence or absence of tumor cells at the end of induction assessed by studying tissue and/or blood/marrow. Details of methods and criteria used can be found in Shiramizu at al. BJH 153:758-763, 2011 (full citation in the citation section).

  • Toxic Death [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Implementation of the toxic death rate stopping rule, a death must be possibly, probably or definitely attributable to Rituximab and/or chemotherapy to be considered a toxic death.
Enrollment: 97
Study Start Date: June 2004
Study Completion Date: July 2014
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
 Drug: doxorubicin hydrochloride
Given IV, IT, or orally
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: methotrexate
Given IV or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: rasburicase
Given IV
Other Names:
  • Elitek
  • NK-631
  • recombinant urate oxidase
Drug: leucovorin calcium
Given IV or orally
Other Names:
  • CF
  • CFR
  • LV
Drug: prednisone
Given IV or orally
Other Names:
  • DeCortin
  • Deltra
Drug: methylprednisolone
Given IV or orally
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Biological: filgrastim
Given subcutaneously
Other Names:
  • G-CSF
  • Neupogen
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: cytarabine
Given IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: hydrocortisone sodium succinate
Given IT
Other Names:
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Other: laboratory biomarker analysis
Correlative studies
Experimental: Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
 Drug: doxorubicin hydrochloride
Given IV, IT, or orally
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: methotrexate
Given IV or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given IV or orally
Other Names:
  • CF
  • CFR
  • LV
Drug: prednisone
Given IV or orally
Other Names:
  • DeCortin
  • Deltra
Drug: methylprednisolone
Given IV or orally
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Biological: filgrastim
Given subcutaneously
Other Names:
  • G-CSF
  • Neupogen
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: cytarabine
Given IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: hydrocortisone sodium succinate
Given IT
Other Names:
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility
Ages Eligible for Study:   1 Year to 29 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed mature B-lineage (CD20-positive) leukemia or lymphoma by the REAL classification of 1 of the following subtypes:

    • Diffuse large cell lymphoma
    • Burkitt's lymphoma
    • High-grade B-cell lymphoma (Burkitt-like)
  • No B-cell anaplastic large cell Ki-1 positive lymphomas and B-lymphoblastic lymphomas

  • One of the following FAB prognostic groups:

    • Group B (intermediate risk)

    • Group C (high risk)

      • Bone marrow involvement with at least 25% blasts and/or CNS involvement meeting 1 or more of the following criteria:

        • Any L3 blasts in cerebrospinal fluid
        • Cranial nerve palsy (if not explained by extracranial tumor)
        • Clinical spinal cord compression
        • Isolated intracerebral mass
        • Parameningeal extension (cranial and/or spinal)
  • Hepatitis B status known
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study participation
  • No known history of congenital immune deficiency and/or laboratory evidence of acquired immune deficiency
  • No known G6PD deficiency (if receiving rasburicase)
  • No prior malignancies treated with systemic chemotherapy with alkylator or anthracycline therapy
  • No prior chemotherapy
  • At least 1 week since prior steroids except emergency steroids initiated within 72 hours of study entry
  • No prior radiotherapy except emergency radiotherapy initiated within 72 hours of study entry
  • No concurrent radiotherapy
  • No prior solid organ transplantation
  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: NCT00057811

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mitchell Cairo, MD CCRP Children's Oncology Group
  More Information

Publications:

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00057811     History of Changes
Other Study ID Numbers: ANHL01P1  NCI-2009-00405  COG-ANHL01P1  CDR0000271941  U10CA098543 
Study First Received: April 7, 2003
Results First Received: January 21, 2014
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Cyclophosphamide
Methotrexate
Cytarabine
Rasburicase
Rituximab
Etoposide phosphate
Liposomal doxorubicin

ClinicalTrials.gov processed this record on September 30, 2016