RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating children who have lymphoma.

Condition	Treatment or Intervention	Phase
stage IV childhood large cell lymphoma stage IV childhood lymphoblastic lymphoma	Drug: cyclophosphamide  Drug: cytarabine  Drug: daunorubicin  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: leucovorin calcium  Drug: methotrexate  Drug: pegaspargase  Drug: prednisone  Drug: thioguanine  Drug: vincristine	Phase II

Further Study Details: 

OBJECTIVES: I. Estimate the toxicity and feasibility of intensifying the New York I (NYI) regimen by adding etoposide and cytarabine, increasing the dose of methotrexate, using pegaspargase, and compressing the treatment duration (11 months) in previously untreated children with disseminated anaplastic (Ki-1 positive) large cell and large cell T-cell lymphoma. II. Provide preliminary data for a future phase III study that will compare this intensified regimen with the high-risk ALL regimen NYI in children with disseminated lymphoblastic lymphoma. III. Continue to investigate the immunophenotype, cytogenetics, and molecular biology of lymphoblastic lymphoma and their relationship to leukemia. IV. Obtain preliminary data on treatment of anaplastic large cell (Ki-1) and T-cell large cell lymphoma treated with intensive NYI.

PROTOCOL OUTLINE: Patients with CNS disease at diagnosis receive craniospinal irradiation on Regimen A at the conclusion of Maintenance chemotherapy. The following acronyms are used: ARA-C Cytarabine, NSC-63878 CF Leucovorin calcium, NSC-3590 CTX Cyclophosphamide, NSC-26271 DNR Daunorubicin, NSC-82151 DOX Doxorubicin, NSC-123127 G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 MTX Methotrexate, NSC-740 PEG-ASP Pegaspargase, NSC-624239 PRED Prednisone, NSC-10023 TG Thioguanine, NSC-752 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540 Induction: 5-Drug Combination Systemic Chemotherapy with Hematopoietic Stimulation plus 2-Drug Combination Intrathecal Chemotherapy. VCR/PRED/CTX/DNR/PEG-ASP; with G-CSF; plus IT ARA-C/IT MTX. Consolidation: 7-Drug Combination Systemic Chemotherapy with Hematopoietic Stimulation plus Single-Agent Intrathecal Chemotherapy. VCR/PRED/PEG-ASP/VP-16/TG/ARA-C/MTX/CF; with G-CSF; plus IT MTX. Maintenance: Sequential Pulses of 2-, 3-, 3-, and 2-Drug Systemic Chemotherapy Combinations plus Single-Agent Intrathecal Chemotherapy. CTX/TG/IT MTX; VCR/PRED/DOX; VCR/MTX/CF/PEG-ASP; ARA-C/VP-16. Regimen A: Radiotherapy. Craniospinal irradiation using megavoltage equipment.

PROJECTED ACCRUAL: 40 patients will be entered over approximately 10 months. If 4 or more toxic deaths occur in the first 15 patients or 5 or more toxic deaths occur in the first 30 patients, accrual will stop. As of 05/96, asparaginase has been replaced with pegaspargase; 15-25 additional patients will be accrued. As of 01/97, a maximum of 35 patients will be accrued for PEG asparaginase-containing treatment regimen. As of 5/97, this study is open only to patients with anaplastic large cell and T cell large cell lymphoma. Approximately 60-90 patients will be accrued.

Ages Eligible for Study:  up to  20 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed and previously untreated anaplastic large cell Ki-1 lymphoma and T-cell large cell lymphoma; Malignant lymphoblasts (identified by immunophenotype) in pleural fluid, ascitic fluid, or bone marrow sufficient for diagnosis
• Large cell lymphoma with T-cell phenotype eligible
• Localized mediastinal disease and bone lymphoma eligible
• CNS disease eligible and defined as: Any clearly identifiable tumor cells in cerebral spinal fluid; Cranial nerve palsy (if not explained by extra cranial tumor); Clinical Spinal Cord Compression; Isolated intra cerebral mass
• No cranial nerve palsies requiring immediate CNS irradiation

--Prior/Concurrent Therapy--

• No prior therapy except emergency treatment of airway obstruction or superior vena cava syndrome; No more than 72 hours between emergency radiotherapy or steroids and initiation of protocol therapy

--Patient Characteristics--

• Age: Under 21
• Performance status: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Cardiovascular: Shortening fraction greater than 27% on echocardiogram (ECHO) OR Left ventricular ejection fraction greater than 47% on radionuclide scan (RCNA) OR Cardiac function assessed as within normal limits by cardiologist; ECHO or RCNA obtained as close as clinically possible to start of therapy

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Orange County, Orange,  California,  92668,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Long Beach Memorial Medical Center, Long Beach,  California,  90806,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
Colorado
      Children's Hospital of Denver, Denver,  Colorado,  80218,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5265,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Missouri
      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States
New Jersey
      St. Joseph's Hospital and Medical Center, Paterson,  New Jersey,  07503,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
North Carolina
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States
      Children's Hospital of Columbus, Columbus,  Ohio,  43205-2696,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Oregon
      Doernbecher Children's Hospital, Portland,  Oregon,  97201-3098,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Tennessee
      Vanderbilt Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84132,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6001,  Australia
Canada, British Columbia
      British Columbia Children's Hospital, Vancouver,  British Columbia,  V6H 3V4,  Canada
Canada, Nova Scotia
      IWK Grace Health Centre, Halifax,  Nova Scotia,  B3J 3G9,  Canada

Study chairs or principal investigators

Minnie Abromowitch,  Study Chair,  Children's Cancer Group   

Study ID Numbers:  CDR0000063751; CCG-5941
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002590
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08