Combination Chemotherapy in Treating Pediatric Patients With Advanced-Stage Large Cell Lymphoma
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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:
Drug: cytarabine
Other Names:
Drug: doxorubicin hydrochloride
Other Names:
Drug: leucovorin calcium
Other Names:
Drug: mercaptopurine
Other Names:
Drug: methotrexate
Other Names:
Drug: prednisone
Other Names:
Drug: vincristine sulfate
Other Names:
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:
Drug: cytarabine
Other Names:
Drug: doxorubicin hydrochloride
Other Names:
Drug: leucovorin calcium
Other Names:
Drug: mercaptopurine
Other Names:
Drug: methotrexate
Other Names:
Drug: prednisone
Other Names:
Drug: vincristine sulfate
Other Names:
Radiation: low-LET cobalt-60 gamma ray therapy
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy
|
Outcome Measures
Primary Outcome Measures
- Event free survival [Length of study]
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).
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Via Christi Regional Medical Center-Saint Francis Campus | Wichita | Kansas | United States | 67214 |
| 2 | MBCCOP - LSU Medical Center | New Orleans | Louisiana | United States | 70112 |
| 3 | Memorial Mission Hospital | Asheville | North Carolina | United States | 28801 |
| 4 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425-0721 |
| 5 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
| 6 | San Antonio Military Pediatric Cancer and Blood Disorders Center | Lackland Air Force Base | Texas | United States | 78236-5300 |
| 7 | University of Texas Health Science Center at San Antonio | San Antonio | Texas | United States | 78284 |
| 8 | Cancer Center, University of Virginia HSC | Charlottesville | Virginia | United States | 22908 |
| 9 | University of Puerto Rico School of Medicine Medical Sciences Campus | San Juan | Puerto Rico | 00936-5067 | |
| 10 | Clinique de Pediatrie | Geneva | Switzerland | 1211 |
Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Study Chair: Joseph H. Laver, MD, Medical University of South Carolina
Study Documents (Full-Text)
None provided.More Information
Publications
- Hutchison RE, Finch C, Kepner J, Fuller C, Bowman P, Link M, Schwenn M, Laver J, Desai S, Barrett D, Murphy SB. Burkitt lymphoma is immunophenotypically different from Burkitt-like lymphoma in young persons. Ann Oncol. 2000;11 Suppl 1:35-8.
- Hutchison RE, Laver JH, Chang M, Muzzafar T, Desai S, Murphy S, Schwenn M, Shuster J, Link MP; Children's Oncology Group. Non-anaplastic peripheral t-cell lymphoma in childhood and adolescence: a Children's Oncology Group study. Pediatr Blood Cancer. 2008 Jul;51(1):29-33. doi: 10.1002/pbc.21543.
- 9315
- POG-9315
- CDR0000063955