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	Treatment or Intervention	Phase
stage III childhood large cell lymphoma stage IV childhood large cell lymphoma childhood diffuse large cell lymphoma AIDS-related diffuse mixed cell lymphoma childhood immunoblastic large cell lymphoma AIDS-related immunoblastic large cell lymphoma AIDS-related peripheral/systemic lymphoma AIDS-related diffuse large cell lymphoma	Drug: cytarabine  Drug: doxorubicin  Drug: filgrastim  Drug: leucovorin calcium  Drug: mercaptopurine  Drug: methotrexate  Drug: prednisone  Drug: vincristine	Phase III

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  up to  21 Years

Criteria

PROTOCOL ENTRY 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)

--Prior/Concurrent Therapy--

• No prior therapy

--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

Kansas
      Via Christi Regional Medical Center-Saint Francis Campus, Wichita,  Kansas,  67214,  United States
Louisiana
      MBCCOP - LSU Medical Center, New Orleans,  Louisiana,  70112,  United States
North Carolina
      Memorial Mission Hospital, Asheville,  North Carolina,  28801,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
Texas
      Medical City Dallas Hospital, Dallas,  Texas,  75230,  United States
      San Antonio Military Pediatric Cancer and Blood Disorders Center, Lackland Air Force Base,  Texas,  78236-5300,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284,  United States
Virginia
      Cancer Center, University of Virginia HSC, Charlottesville,  Virginia,  22908,  United States
Puerto Rico
      University of Puerto Rico School of Medicine Medical Sciences Campus, San Juan,  00936-5067,  Puerto Rico
Switzerland
      Clinique de Pediatrie, Geneva,  1211,  Switzerland

Study chairs or principal investigators

Joseph Laver,  Study Chair,  Pediatric Oncology Group   

Study ID Numbers:  CDR0000063955; POG-9315
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002618
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08