RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy followed by melphalan and peripheral stem cell transplantation in treating children who have newly diagnosed acute myeloid leukemia that has not been treated previously.

Condition	Treatment or Intervention	Phase
childhood acute megakaryocytic leukemia (M7) untreated childhood acute myeloid leukemia childhood acute minimally differentiated myeloid leukemia (M0) childhood acute erythroleukemia (M6) childhood acute myelomonocytic leukemia (M4) childhood acute monocytic leukemia (M5) childhood acute myeloblastic leukemia without maturation (M1) childhood acute myeloblastic leukemia with maturation (M2)	Drug: asparaginase  Drug: cytarabine  Drug: daunorubicin  Drug: filgrastim  Drug: melphalan  Drug: thioguanine	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the feasibility and toxicity of timed sequential remission induction and consolidation in children with newly diagnosed acute myeloid leukemia. II. Determine the feasibility and toxicity of a single high dose of melphalan with peripheral blood stem cell rescue following an intense timed sequential induction and consolidation in these children.

PROTOCOL OUTLINE: This is a multicenter study. Remission induction: Patients receive daunorubicin IV over 15 minutes on days 1-3, cytarabine IV continuously on days 1-7, oral thioguanine daily on days 1-7, and cytarabine intrathecally (IT) on day 1. Cytarabine IV over 3 hours is administered every 12 hours on days 10-12. Filgrastim (G-CSF) is administered IV or subcutaneously (SQ) beginning on day 13 and continuing until blood counts recover. On approximately day 28, patients undergo a bone marrow aspirate and biopsy to assess response. Patients who have attained an M1 or M2a status proceed to consolidation or, if a 5/5 or 6/6 HLA matched sibling donor is available, proceed to allogeneic bone marrow transplantation. Patients with greater than 25% blasts go off study. Consolidation 1: Patients receive daunorubicin IV over 15 minutes on days 1 and 2, cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, and asparaginase on days 2 and 9. G-CSF IV or SQ begins on day 10 and continues until blood counts recover. Consolidation 2: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. G-CSF IV or SQ begins on day 6 and continues until blood counts recover. Peripheral blood stem cells (PBSC) are collected after the second course of consolidation. Consolidation 3: Treatment is repeated as in consolidation 1. Patients who remain in morphologic remission after consolidation 3 proceed with therapy. Patients receive melphalan IV over 30 minutes on day -2, then PBSC are reinfused on day 0. G-CSF IV or SQ begins on day 1 and continues until blood counts recover. Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for this study within 8 months.

Ages Eligible for Study:  up to  21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven, previously untreated primary acute myeloid leukemia (AML); Isolated granulocytic sarcoma (myeloblastoma) allowed; Patients with cytopenias and bone marrow blasts greater than 5% but less than 30% eligible only if there is karyotypic abnormality characteristic of de novo AML (t(8;21), inv16, t(9;11), etc.) OR unequivocal presence of megakaryoblasts
• No acute promyelocytic leukemia (M3)
• No Down syndrome

--Prior/Concurrent Therapy--

• No prior therapy

--Patient Characteristics--

• Age: 21 and under
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 3 times upper limit of normal
• Renal: Creatinine no greater than 1.5 mg/dL; Uric acid no greater than 8.0 mg/dL
• Cardiovascular: Cardiac function normal by echocardiogram
• Pulmonary: No uncontrolled, life threatening pneumonia
• Other: No uncontrolled, life threatening sepsis or meningitis; Not pregnant; Fertile patients must use effective contraception

Alabama
      University of Alabama Comprehensive Cancer Center, Birmingham,  Alabama,  35294,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Children's Hospital and Health Center, San Diego,  California,  92123-4282,  United States
      Lucile Packard Children's Hospital at Stanford, Palo Alto,  California,  94304,  United States
Florida
      Nemours Children's Clinic, Jacksonville,  Florida,  32207,  United States
Georgia
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States
Illinois
      Children's Memorial Hospital, Chicago, Chicago,  Illinois,  60614,  United States
Maine
      Maine Children's Cancer Program, Scarborough,  Maine,  04074,  United States
Maryland
      Johns Hopkins Oncology Center, Baltimore,  Maryland,  21231,  United States
Massachusetts
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States
Michigan
      Children's Hospital of Michigan, Detroit,  Michigan,  48201,  United States
Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
      Tomorrows Children's Institute, Hackensack,  New Jersey,  07601,  United States
New York
      Mount Sinai School of Medicine, New York,  New York,  10029,  United States
Texas
      Cook Children's Medical Center - Fort Worth, Fort Worth,  Texas,  76104,  United States
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
Wisconsin
      Midwest Children's Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
Canada, Quebec
      Montreal Children's Hospital, Montreal,  Quebec,  H3H 1P3,  Canada

Study chairs or principal investigators

Craig A. Hurwitz,  Study Chair,  National Cancer Institute (NCI)   

Study ID Numbers:  CDR0000067253; POG-9822
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004056
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08