Combination Chemotherapy in Treating Pediatric Patients With Advanced-Stage Large Cell Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002618
First received: November 1, 1999
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different doses may kill more cancer cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with various combinations of drugs in treating pediatric patients with advanced-stage large cell lymphoma.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Drug: cytarabine
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: prednisone
Drug: vincristine sulfate
Radiation: low-LET cobalt-60 gamma ray therapy
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase III Study of Large Cell Lymphomas in Children and Adolescents: Comparison of APO vs APO + IDMTX/HDARA-C and Continuous vs Bolus Infusion of Doxorubicin

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event free survival [ Time Frame: Length of study ] [ Designated as safety issue: No ]
    To study whether intermediate-dose methotrexate/high-dose Ara-C (ID MTX/HDAra-C), administered during the maintenance phase can improve the event free survival (EFS) of patients with advanced-stage large cell lymphoma (LCL).


Estimated Enrollment: 242
Study Start Date: December 1994
Study Completion Date: September 2006
Primary Completion Date: September 2000 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
Biological: filgrastim
Other Names:
  • rmetHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cytarabine
Other Names:
  • CYTOSINE ARABINOSIDE
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: mercaptopurine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #755
Drug: methotrexate
Other Names:
  • amethopterin
  • NSC #740
Drug: prednisone
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #10023
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET electron therapy Radiation: low-LET photon therapy
Active Comparator: Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
Biological: filgrastim
Other Names:
  • rmetHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cytarabine
Other Names:
  • CYTOSINE ARABINOSIDE
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: mercaptopurine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #755
Drug: methotrexate
Other Names:
  • amethopterin
  • NSC #740
Drug: prednisone
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #10023
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET electron therapy Radiation: low-LET photon therapy

Detailed Description:

OBJECTIVES: I. Compare the event free survival of children with advanced stage large cell lymphoma treated with modified APO (doxorubicin/prednisone/vincristine/mercaptopurine) with or without intermediate-dose methotrexate/high dose cytarabine as maintenance therapy following induction therapy with APO. II. Characterize further the immunophenotypic and morphologic correlates of pediatric large cell lymphoma.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms, except for those with CNS disease. These patients are assigned to arm II and receive whole brain irradiation on Regimen B. Arm I: Induction (Modified APO): Patients receive vincristine IV on days 1, 8, 15, 22, and 29, doxorubicin IV over 15 minutes on days 1 and 22, prednisone three times a day on days 1-28, and methotrexate intrathecally (IT) on days 1, 8, and 22. Patients in complete remission on day 43 proceed to maintenance, those in partial remission undergo biopsy then proceed to maintenance, and those with residual disease receive radiotherapy on regimen A concurrently with maintenance. Maintenance (day 1 is day 43 of Induction): Courses of intermediate dose methotrexate/leucovorin calcium and high dose cytarabine (ID MTX/CF/HD ARA-C) and modified APO alternate every 3 weeks. Patients receive a total of 15 courses (8 of ID MTX/CF/HD ARA-C and 7 of Modified APO). ID MTX/CF/HD ARA-C: Patients receive methotrexate IV over 24 hours on day 1, leucovorin calcium IV or orally every 6 hours on days 2 and 3, cytarabine IV over 48 hours on days 2 to 4, and methotrexate IT on day 1 of courses 1, 3, and 5. Filgrastim (G-CSF) is administered beginning on day 5 and continuing until blood counts recover. Modified APO: Patients receive vincristine IV on day 1, oral mercaptopurine on days 1-5, doxorubicin IV over 15 minutes on day 1, and oral prednisone three times a day on days 1-5. Arm II: Induction: Patients receive treatment as in arm I except that patients with CNS disease also receive methotrexate IT on days 15, 29, and 36. Maintenance (day 1 is day 43 of Induction): Modified APO: as in Arm I, with methotrexate administered on day 1 of courses 1, 3, and 5 (days 1-5 for patients with CNS disease). Courses repeat every 21 days for a total of 15 courses. Patients with CNS disease begin radiotherapy on Regimen B on week 2 of maintenance. Regimen A: Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance. Regimen B: Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.

PROJECTED ACCRUAL: A total of 242 patients will be accrued for this study over approximately 5.4 years.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Previously untreated large cell lymphoma, including the following histologic designations: Rappaport classification Diffuse histiocytic Mixed lymphocytic-histiocytic Working Formulation classification Diffuse large cell, cleaved and/or noncleaved Immunoblastic Diffuse, mixed small and large cell Lukes-Collins classification Diffuse large cleaved Diffuse large noncleaved Immunoblastic T or B cell True histiocytic Updated Kiel classification Cytocentric large cell Centroblastic-centrocytic T-zone Lymphoepithelioid cell (Lennert's) Immunoblastic T or B cell Large cell anaplastic Pleomorphic Centroblastic-centrocytic, diffuse Malignant histiocytosis Murphy stage III/IV HIV-associated lymphoma eligible Any degree of bone marrow involvement eligible CNS disease eligible (such patients not randomized)

PATIENT CHARACTERISTICS: Age: Under 22 Performance status: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing Adequate contraception required of fertile patients

PRIOR CONCURRENT THERAPY: No prior therapy

  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: NCT00002618

Locations
United States, Kansas
Via Christi Regional Medical Center-Saint Francis Campus
Wichita, Kansas, United States, 67214
United States, Louisiana
MBCCOP - LSU Medical Center
New Orleans, Louisiana, United States, 70112
United States, North Carolina
Memorial Mission Hospital
Asheville, North Carolina, United States, 28801
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425-0721
United States, Texas
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
San Antonio Military Pediatric Cancer and Blood Disorders Center
Lackland Air Force Base, Texas, United States, 78236-5300
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284
United States, Virginia
Cancer Center, University of Virginia HSC
Charlottesville, Virginia, United States, 22908
Puerto Rico
University of Puerto Rico School of Medicine Medical Sciences Campus
San Juan, Puerto Rico, 00936-5067
Switzerland
Clinique de Pediatrie
Geneva, Switzerland, 1211
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Joseph H. Laver, MD Medical University of South Carolina
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002618     History of Changes
Other Study ID Numbers: 9315, POG-9315, CDR0000063955
Study First Received: November 1, 1999
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related diffuse large cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related diffuse mixed cell lymphoma
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Doxorubicin
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antibiotics, Antineoplastic
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 23, 2014