RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and combining drugs in different ways may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy in treating children who have very high risk acute lymphocytic leukemia.

Condition	Treatment or Intervention	Phase
L2 childhood acute lymphoblastic leukemia untreated childhood acute lymphoblastic leukemia L1 childhood acute lymphoblastic leukemia B-cell childhood acute lymphoblastic leukemia	Drug: asparaginase  Drug: cyclophosphamide  Drug: cytarabine  Drug: daunorubicin  Drug: dexamethasone  Drug: etoposide  Drug: filgrastim  Drug: idarubicin  Drug: leucovorin calcium  Drug: mercaptopurine  Drug: methotrexate  Drug: prednisone  Drug: vincristine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the feasibility of administering a new combination of agents during postinduction consolidation therapy in children with very high risk acute lymphocytic leukemia (VHR-ALL). II. Assess the tolerance of patients in remission of VHR-ALL for postconsolidation therapy with continuous intensification.

PROTOCOL OUTLINE: Patients receive induction therapy on weeks 1-4. This consists of oral prednisone three times a day on days 1-28; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, and 22; and asparaginase IM on days 2, 5, 8, 12, 15, and 19. Patients also receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS 2 and 3 disease also receive methotrexate IT on days 15 and 22. Patients who achieve M2 bone marrow on day 29 receive oral prednisone three times a day on days 29-42; vincristine IV and daunorubicin IV over 15 minutes on days 29 and 36; and asparaginase IM on days 29, 32, 36, and 39. If bone marrow is M3 on day 29 or M2 or M3 on day 43, then patient is off study. Patients proceed to consolidation therapy on weeks 5-25. This consists of high dose methotrexate IV over 24 hours on weeks 6, 8, 16, and 18, followed by leucovorin calcium IV or orally every 6 hours for 5 doses; oral mercaptopurine on weeks 6-9 and 16-19; cytarabine IV over 6 hours followed by idarubicin IV over 15 minutes for 4 days; and filgrastim (G-CSF) subcutaneously (SQ) beginning on day 5 and continuing for about 10-14 days on weeks 10 and 20. Patients receive etoposide IV over 1 hour followed by cyclophosphamide IV over 10 minutes for 5 days and G-CSF SQ beginning on day 6 for 10-14 days on weeks 13 and 23. Methotrexate IT is administered on weeks 6, 8, 13, 16, 18, and 23. Patients then proceed to continuous intensification therapy during weeks 26-61. Patients receive vincristine IV, daunorubicin IV, and methotrexate IT on day 1, and oral dexamethasone twice a day on days 1-7 on weeks 26, 32, 38, 44, 50, and 56. Patients also receive high dose cytarabine IV over 1 hour, every 12 hours, for 4 doses, followed by asparaginase IM 3 hours after the last dose of cytarabine, on weeks 27, 33, 39, 45, 51, and 57. Oral mercaptopurine and methotrexate IM are administered on day 1 during weeks 29, 31, 35, 37, 41, 43, 47, 49, 53, 55, 59, and 61. Patients receive etoposide IV over 1-2 hours followed by cyclophosphamide IV during weeks 30, 36, 42, 48, 54, and 60. Patients then proceed to continuation therapy during weeks 62-126. Vincristine IV and cyclophosphamide IV are administered on weeks 62-65, 70-73, 78-81, 86-89, 94-97, 102-105, 110-113, and 118-121. Patients also receive oral dexamethasone twice a day for 7 days on weeks 62, 70, 78, 86, 94, 102, 110, and 118, and cytarabine IV on weeks 63, 65, 71, 73, 79, 81, 87, 89, 95, 97, 103, 105, 111, 113, 119, and 121. Oral mercaptopurine is administered daily during weeks 66-69, 74-77, 82-85, 90-93, 98-101, 106-109, 114-117, and 122-125 and methotrexate IM on weeks 66-69, 74-77, 82-85, 90-93, 98-101, 106-109, 114-117, and 122-125. Methotrexate IT is administered during weeks 62, 70, 78, 86, 94, 102, 110, and 118. Patients who are CNS 3 at diagnosis receive whole brain irradiation beginning at week 62 along with the first course of continuation therapy. These patients do not receive any methotrexate IT after week 62. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, then annually thereafter.

PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study within 12 months.

Ages Eligible for Study:  up to  17 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Newly diagnosed B-cell precursor acute lymphocytic leukemia; No L3 morphology
• Very poor prognosis CNS 3 (blasts and WBC greater than 5 microliters) OR Must meet all of the following criteria: No simultaneous trisomy 4 and 10 DNA index no greater than 1.16 (if FISH 4 and 10 unsatisfactory); No TEL-AML1 [t(12;21)] Meets at least 1 of the following: Has MLL (11q23) and/or BCR-ABL [t(9;22)] WBC greater than 100,000/mm3; Age over 12 (boys) or 16 (girls) OR Boys 8 or Girls 12 with WBC greater than 80,000/mm3; Boys 9 or Girls 13 with WBC greater than 60,000/mm3; Boys 10 or Girls 14 with WBC greater than 40,000/mm3; Boys 11 or Girls 15 with WBC greater than 20,000/mm3
• Concurrent registration on stratum 6 of POG-9400 before 11/15/1999 OR Concurrent registration on stratum 4 of POG-9900 after 11/15/1999; Concurrent registration on POG-9201, POG-9705, or POG-9806 unless ineligible

--Prior/Concurrent Therapy--

• See Disease Characteristics

--Patient Characteristics--

• Age: Children
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics
• Hepatic: Not specified
• Renal: Not specified

Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
California
      Kaiser Permanente Medical Center - Santa Clara, Santa Clara,  California,  95051-5386,  United States
      Kaiser Permanente-Southern California Permanente Medical Group, San Diego,  California,  92120,  United States
      Lucile Packard Children's Hospital at Stanford, Palo Alto,  California,  94304,  United States
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States
      Sutter Cancer Center, Sacramento,  California,  95816,  United States
Florida
      Baptist Hospital of Miami, Miami,  Florida,  33176-2197,  United States
      Mount Sinai Comprehensive Cancer Center, Miami Beach,  Florida,  33140,  United States
      Nemours Children's Clinic, Jacksonville,  Florida,  32207,  United States
      St. Mary's Hospital, West Palm Beach,  Florida,  33407,  United States
      Sylvester Cancer Center, University of Miami, Miami,  Florida,  33136,  United States
      Walt Disney Memorial Cancer Institute, Orlando,  Florida,  32803,  United States
Georgia
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States
Hawaii
      Tripler Army Medical Center, Honolulu,  Hawaii,  96859-5000,  United States
Illinois
      Children's Memorial Hospital, Chicago, Chicago,  Illinois,  60614,  United States
      Hope Children's Hospital, Oak Lawn,  Illinois,  60453,  United States
      Rush-Presbyterian-St. Luke's Medical Center, Chicago,  Illinois,  60612,  United States
      Saint Jude Midwest Affiliate, Peoria,  Illinois,  61602,  United States
Kansas
      Via Christi Regional Medical Center, Wichita,  Kansas,  67214,  United States
Louisiana
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maine
      Eastern Maine Medical Center, Bangor,  Maine,  04401,  United States
      Maine Children's Cancer Program, Portland,  Maine,  04101,  United States
Massachusetts
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States
Michigan
      Hurley Medical Center, Flint,  Michigan,  48503,  United States
      St. John's Hospital and Medical Center, Detroit,  Michigan,  48236,  United States
Mississippi
      Keesler Medical Center - Keesler AFB, Keesler AFB,  Mississippi,  39534-2576,  United States
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      University of Missouri-Columbia Hospital and Clinics, Columbia,  Missouri,  65212,  United States
      Washington University School of Medicine, Saint Louis,  Missouri,  63110,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756,  United States
New Mexico
      University of New Mexico School of Medicine, Albuquerque,  New Mexico,  87131,  United States
New York
      State University of New York Health Sciences Center - Stony Brook, Stony Brook,  New York,  11790-7775,  United States
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
Oklahoma
      Natalie Warren Bryant Cancer Center, Tulsa,  Oklahoma,  74136,  United States
      Oklahoma Memorial Hospital, Oklahoma City,  Oklahoma,  73126-0307,  United States
Tennessee
      James H. Quillen College of Medicine, Johnson City,  Tennessee,  37614-0622,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
      Cook Children's Medical Center - Fort Worth, Fort Worth,  Texas,  76104,  United States
      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
      Scott and White Clinic, Temple,  Texas,  76508,  United States
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0209,  United States
Vermont
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
Virginia
      Carilion Roanoke Community Hospital, Roanoke,  Virginia,  24029,  United States
      Inova Fairfax Hospital, Falls Church,  Virginia,  22046,  United States
Washington
      Madigan Army Medical Center, Tacoma,  Washington,  98431-5000,  United States
West Virginia
      West Virginia University Hospitals, Morgantown,  West Virginia,  26506-9162,  United States
      West Virginia University Medical School, Charleston Division, Charleston,  West Virginia,  25304,  United States
Wisconsin
      Midwest Children's Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
      St. Vincent Hospital, Green Bay,  Wisconsin,  54307-3508,  United States
Canada, Alberta
      Alberta Children's Hospital, Calgary,  Alberta,  T2T 5C7,  Canada
Canada, Ontario
      Children's Hospital of Eastern Ontario, Ottawa,  Ontario,  K1H 8L1,  Canada
Canada, Quebec
      Centre Hospitalier de L'Universite Laval, Sainte-Foy,  Quebec,  GIV 4G2,  Canada
      Montreal Children's Hospital, Montreal,  Quebec,  H3H 1P3,  Canada
Netherlands
      Academisch Ziekenhuis Groningen, Groningen,  9713 EZ,  Netherlands
Puerto Rico
      San Jorge Childrens Hospital, Santurce,  00912,  Puerto Rico
Switzerland
      Clinique de Pediatrie, Geneva,  1211,  Switzerland

Study chairs or principal investigators

William Paul Bowman,  Study Chair,  Pediatric Oncology Group   

Study ID Numbers:  CDR0000066915; POG-9806
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003783
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08