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

July 23, 2014 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

242

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

Arms and Interventions

Participant Group / 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.
Drug: leucovorin calcium
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: prednisone
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #10023
Drug: cytarabine
Other Names:
  • Ara-C
  • Cytosar
  • NSC #63878
  • CYTOSINE ARABINOSIDE
Drug: methotrexate
Other Names:
  • amethopterin
  • NSC #740
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
Drug: mercaptopurine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #755
Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC #123127
Biological: filgrastim
Other Names:
  • G-CSF
  • Neupogen
  • NSC #614629
  • rmetHuG-CSF
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy
Radiation: low-LET cobalt-60 gamma ray 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.
Drug: leucovorin calcium
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: prednisone
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #10023
Drug: cytarabine
Other Names:
  • Ara-C
  • Cytosar
  • NSC #63878
  • CYTOSINE ARABINOSIDE
Drug: methotrexate
Other Names:
  • amethopterin
  • NSC #740
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
Drug: mercaptopurine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #755
Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC #123127
Biological: filgrastim
Other Names:
  • G-CSF
  • Neupogen
  • NSC #614629
  • rmetHuG-CSF
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy
Radiation: low-LET cobalt-60 gamma ray therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event free survival
Time Frame: 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).
Length of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Joseph H. Laver, MD, Medical University of South Carolina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1994

Primary Completion (Actual)

September 1, 2000

Study Completion (Actual)

September 1, 2006

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

July 28, 2004

First Posted (Estimate)

July 29, 2004

Study Record Updates

Last Update Posted (Estimate)

July 24, 2014

Last Update Submitted That Met QC Criteria

July 23, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9315
  • POG-9315 (Other Identifier: Pediatric Oncology Group)
  • CDR0000063955 (Other Identifier: NCI)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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