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 combinations may kill more cancer cells. Bone marrow transplantation allows the doctor to give higher doses of chemotherapy and kill more cancer cells.

PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without donor bone marrow transplantation in treating infants who have previously untreated acute lymphoblastic leukemia.

Condition	Treatment or Intervention	Phase
untreated childhood acute lymphoblastic leukemia L1 childhood acute lymphoblastic leukemia L2 childhood acute lymphoblastic leukemia acute undifferentiated leukemia	Drug: asparaginase  Drug: cyclophosphamide  Drug: cyclosporine  Drug: cytarabine  Drug: daunorubicin  Drug: dexamethasone  Drug: doxorubicin  Drug: mercaptopurine  Drug: methotrexate  Drug: methylprednisolone  Drug: pegaspargase  Drug: thioguanine  Drug: vincristine  Procedure: allogeneic bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: radiation therapy  Procedure: steroid therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the feasibility of dexamethasone-based induction chemotherapy followed by augmented Berlin-Frankfurt-Munster (BFM) consolidation chemotherapy with or without allogeneic bone marrow transplantation in infants with previously untreated acute lymphoblastic leukemia.
• Determine the event-free survival of patients treated with this regimen.
• Determine the clinical prognostic features associated with outcome in these patients.
• Compare the biologic characteristics of the leukemia cells with outcome in these patients.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising oral dexamethasone 3 times daily on days 1-14; daunorubicin IV on days 1, 8, and 15; vincristine IV on days 1, 8, 15, and 22; and asparaginase intramuscularly (IM) on days 4, 6, 8, 11, 13, 15, 18, 20, and 22. Patients also receive methotrexate intrathecally (IT) on days 1, 8, and 15 (and days 4 and 22 for overt CNS disease).

Patients with M1 or M2 marrow after induction therapy receive augmented consolidation therapy when blood counts recover. Patients receive cyclophosphamide IV on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 2-5, 9-12, 30-33, and 37-40; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43; and methotrexate IT on days 1, 8, and 15.

Patients who do not receive bone marrow transplantation (BMT) proceed to interim maintenance #1 when blood counts recover. Patients receive methotrexate IT on days 1, 11, 22, and 32; methotrexate IV and vincristine IV on days 1, 11, 22, 32, and 43; and pegaspargase IM on days 2 and 23.

When blood counts recover, patients receive delayed intensification #1 comprising vincristine IV on days 1, 8, 15, 43, and 50; doxorubicin IV on days 1, 8, and 15; oral dexamethasone 3 times daily on days 1-7 and 15-21; pegaspargase IM on days 4 and 43; cyclophosphamide IV on day 29; methotrexate IT on days 29 and 36; oral thioguanine on days 29-42; and cytarabine IV or SC on days 30-33 and 37-40.

When blood counts recover, patients receive interim maintenance #2 comprising vincristine as in interim maintenance #1; methotrexate IT on day 1 and IV on days 1, 11, 22, 32, and 41; and pegaspargase IM on days 2 and 23.

When blood counts recover, patients receive delayed intensification #2 comprising vincristine, doxorubicin, dexamethasone, pegaspargase, cyclophosphamide, cytarabine, and thioguanine as in intensification #1. Patients also receive methotrexate IT on days 1 and 29.

When blood counts recover, patients receive maintenance therapy comprising methotrexate IT on day 1 and orally on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; vincristine IV on days 1, 29, and 57; oral dexamethasone 3 times daily on days 1-5, 29-33, and 57-61; and oral mercaptopurine daily. Treatment repeats every 84 days for 6 courses.

Patients with an allergy to pegaspargase replace it with asparaginase IM on the days after receiving methotrexate IV during interim maintenance #1 and #2 and daily over 6 days in place of each dose of pegaspargase during delayed intensification #1 and #2.

After augmented consolidation therapy, patients meeting the following criteria may receive BMT in place of chemotherapy:

• In remission
• Exhibiting chromosome translocation involving 11q23 or Ph+{(9;22)}
• Available HLA-A, B, DR genotypic identical relative donor
• No uncontrolled infection
• Adequate organ function Within 3-4 weeks of consolidation therapy, patients undergoing allogeneic BMT receive cytarabine IV over 1 hour on days -8 to -5; cyclophosphamide IV over 30 minutes on days -7 and -6; and methylprednisolone IV twice daily on days -2 to 0. Patients also undergo total body irradiation twice daily on days -3 to 0. Patients receive allogeneic BMT on day 0. Patients also receive cyclosporine IV every 12 hours beginning on day -1, switching to oral when possible, and continuing until day 60. Patients then taper cyclosporine over the next 60-120 days.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1-2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 20-40 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  up to  1 Year,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of previously untreated acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia
• CNS or testicular disease allowed
• No L3 sIg+ ALL or acute myelogenous leukemia
• At least 36 weeks gestation for congenital ALL

PATIENT CHARACTERISTICS: Age:

• Under 366 days at diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Steroid therapy within 48 hours of study allowed if complete blood counts and lumbar puncture results known
• No chronic steroid treatment for other disease

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No other concurrent cytotoxic therapy

Arizona
      Phoenix Children's Hospital, Phoenix,  Arizona,  85016,  United States
California
      Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center, Orange,  California,  92868,  United States
      Children's Hospital Central California, Madera,  California,  93638-8762,  United States
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Oakland, Oakland,  California,  94609-1809,  United States
      Children's Hospital of Orange County, Orange,  California,  92868,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Loma Linda University Medical Center, Loma Linda,  California,  92354,  United States
Colorado
      Children's Hospital of Denver, Denver,  Colorado,  80218-1088,  United States
Connecticut
      University of Connecticut Health Center, Farmington,  Connecticut,  06360-7106,  United States
Delaware
      Alfred I. duPont Hospital for Children, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Georgia
      Children's Healthcare of Atlanta - Scottish Rite, Atlanta,  Georgia,  30342,  United States
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60601,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
      John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States
Louisiana
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0914,  United States
Minnesota
      Children's Hospitals and Clinics - Minneapolis, Minneapolis,  Minnesota,  55404,  United States
      Children's Hospitals and Clinics - Minnesota, Saint Paul,  Minnesota,  55102,  United States
Missouri
      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States
New Jersey
      Cancer Institute of New Jersey, New Brunswick,  New Jersey,  08903,  United States
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
      Mount Sinai School of Medicine, New York,  New York,  10029,  United States
North Carolina
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
Ohio
      Children's Hospital Medical Center of Akron, Akron,  Ohio,  44308,  United States
      Children's Hospital of Columbus, Columbus,  Ohio,  43205-2696,  United States
      Children's Medical Center - Dayton, Dayton,  Ohio,  45404,  United States
      Cincinnati Children's Hospital Medical Center, Cincinnati,  Ohio,  45229-3039,  United States
Oregon
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States
      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
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Methodist Cancer Center, San Antonio,  Texas,  78229-3902,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
      Deaconess Medical Center, Spokane,  Washington,  99210-0248,  United States
      Madigan Army Medical Center, Tacoma,  Washington,  98431-5000,  United States
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
Australia, South Australia
      Women's and Children's Hospital, North Adelaide,  South Australia,  5006,  Australia
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6006,  Australia
Canada, British Columbia
      British Columbia Children's Hospital, Vancouver,  British Columbia,  V6H 3V4,  Canada
Canada, Nova Scotia
      IWK Health Centre, Halifax,  Nova Scotia,  B3J 3G9,  Canada

Study chairs or principal investigators

Paul S. Gaynon, MD,  Study Chair,  Children's Hospital Los Angeles   

Study ID Numbers:  CDR0000068787; COG-AALL01P1
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  August 10, 2001
ClinicalTrials.gov Identifier:  NCT00022126
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08