RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of peripheral stem cell transplantation following chemotherapy in treating patients with acute myeloid leukemia in second remission.

Condition	Treatment or Intervention	Phase
adult acute differentiated monocytic leukemia (M5b) adult acute myeloblastic leukemia without maturation (M1) adult acute minimally differentiated myeloid leukemia (M0) adult acute poorly differentiated monocytic leukemia (M5a) adult acute erythroleukemia (M6) adult acute myeloid leukemia in remission adult acute myelomonocytic leukemia (M4) adult acute myeloblastic leukemia with maturation (M2) adult acute megakaryocytic leukemia (M7) adult acute promyelocytic leukemia (M3)	Drug: busulfan  Drug: cytarabine  Drug: etoposide  Drug: filgrastim  Drug: methotrexate	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the ability of mobilization using cytarabine, etoposide, and filgrastim (G-CSF), conditioning using busulfan and etoposide, and autologous peripheral blood stem cell transplantation to generate a 2-year disease-free survival rate in at least 30% of patients with acute myeloid leukemia (AML) in second complete remission. II. Determine whether the treatment-related mortality can be limited to less than 20% in patients treated with this regimen. III. Determine whether adequate numbers of PBSC can be collected in these patients. IV. Determine the engraftment kinetics of primed PBSC obtained from these patients.

PROTOCOL OUTLINE: Mobilization/harvest: Patients receive cytarabine IV over 2 hours every 12 hours and etoposide IV continuously on days 1-4. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 14 and continuing until peripheral blood stem cells (PBSC) are harvested. When blood counts recover, PBSC are harvested and selected for CD34+ cells. Conditioning: Beginning at least 4 weeks after hospital discharge for mobilization and harvest and when blood counts recover, patients receive oral busulfan every 6 hours on days -7 to -4 and etoposide IV over 4 hours on day -3. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Patients with documented CNS disease at first relapse receive methotrexate intrathecally at intervals of 1 week or greater before and/or after PBSC transplantation for a total of 6 doses. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 26-48 patients will be accrued within 2 years.

Ages Eligible for Study:  15 Years   -   69 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of acute myeloid leukemia (AML) in second complete remission (CR) for 30 days to less than 1 year before study entry; Second CR defined by the following: Neutrophil count at least 1,000/mm3; Platelet count at least 100,000/mm3; Normal bone marrow morphology with no excess blasts (greater than 5%); No myelodysplasia; No extramedullary or CNS leukemia
• Initial diagnosis of de novo AML (M0-M7); No prior myelodysplasia; No myeloproliferative disease; No secondary AML
• Cytogenetics not required; No cytogenetic evidence of persistent leukemia if cytogenetics performed

--Prior/Concurrent Therapy--

• Biologic therapy: No prior bone marrow/stem cell transplantation
• Chemotherapy: Prior non-ablative chemotherapy at initial diagnosis, during initial remission, or as reinduction therapy (to produce current second remission) allowed; At least 4 weeks since hospital discharge after reinduction therapy
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: No prior post-remission therapy for second remission

--Patient Characteristics--

• Age: 15 to 69
• Hematopoietic: See Disease Characteristics; Granulocyte count at least 1,000/mm3
• Hepatic: Bilirubin less than 1.5 mg/dL; AST less than 3 times normal; Alkaline phosphatase less than 3 times normal; No cirrhosis or chronic hepatitis; Biopsy required if chronic liver disease suspected (history of alcohol abuse or possible hepatitis)
• Renal: Creatinine less than 2.0 mg/dL
• Other: Not pregnant or nursing; Fertile patients must use effective contraception

California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
New Jersey
      St. Joseph's Hospital and Medical Center, Paterson,  New Jersey,  07503,  United States

Study chairs or principal investigators

Charles A. Linker,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000064734; CLB-9620
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002768
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08