RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Biological therapies use different ways to stimulate the immune system and stop cancer cell from growing. Combining more than one chemotherapy drug with biological therapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, isotretinoin, and interferon alfa in treating patients who have acute myelogenous leukemia.

Condition	Treatment or Intervention	Phase
untreated adult acute myeloid leukemia childhood acute megakaryocytic leukemia (M7) adult acute differentiated monocytic leukemia (M5b) adult acute myeloblastic leukemia without maturation (M1) untreated childhood acute myeloid leukemia adult acute poorly differentiated monocytic leukemia (M5a) adult acute erythroleukemia (M6) adult acute myelomonocytic leukemia (M4) childhood acute poorly differentiated monocytic leukemia (M5a) childhood acute erythroleukemia (M6) adult acute myeloblastic leukemia with maturation (M2) childhood acute myelomonocytic leukemia (M4) childhood acute differentiated monocytic leukemia (M5b) childhood acute myeloblastic leukemia without maturation (M1) childhood acute myeloblastic leukemia with maturation (M2) adult acute megakaryocytic leukemia (M7)	Drug: amifostine  Drug: broxuridine  Drug: cytarabine  Drug: idarubicin  Drug: idoxuridine  Drug: interferon alfa  Drug: isotretinoin  Drug: mitoxantrone	Phase II

Further Study Details: 

OBJECTIVES: I. Assess the efficacy of high dose cytarabine with mitoxantrone and amifostine as induction therapy for patients with previously untreated standard risk acute myelogenous leukemia (AML). II. Assess the effects of amifostine on the biology of AML cells in vivo in these patients. III. Determine whether there is a relationship between cytokine production before and during remission induction therapy and treatment outcome.

PROTOCOL OUTLINE: Prior to treatment, patients undergo bone marrow aspirate and biopsy. On day -3, patients receive idoxuridine IV over 60 minutes followed immediately by a bone marrow aspirate and biopsy. Patients then receive amifostine IV over 5-7 minutes on the same day. Prior to chemotherapy on day 1, patient receive broxuridine IV over 60 minutes immediately followed by bone marrow aspirate and biopsy. Chemotherapy on day 1 consists of amifostine followed by cytarabine IV over 3 hours repeated every 12 hours and mitoxantrone IV over 1 hour immediately after the second infusion of cytarabine. This course is repeated on day 5 after another bone marrow biopsy and aspirate. Starting on day 6, patients receive amifostine 3 times a week until day 28 or beyond. Patients who respond to treatment continue on to receive three courses of consolidation therapy. Consolidation courses 1 and 3 consist of cytarabine continuous IV on days 1-7 and idarubicin IV over 30 minutes on days 1, 2, and 3. Consolidation course 2 consists of cytarabine IV over 75 minutes repeated every 12 hours for 4 days. Twenty-four hours after each course of consolidation therapy, patients receive isotretinoin orally every day and interferon alfa subcutaneously every other day. Isotretinoin and interferon alfa therapy are stopped 4 days prior to day 1 of the next course of consolidation therapy. Following recovery from course 3 of consolidation therapy, patients continue to receive isotretinoin/interferon alfa until relapse. Patients in complete remission after the 3 courses of consolidation therapy receive isotretinoin/interferon alfa for 3 years. Patients are followed every 3 months for the first year, then every 6 months for the next 2 years.

PROJECTED ACCRUAL: There will be 40-45 patients accrued into this study.

Ages Eligible for Study:  up to  70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed previously untreated acute myelogenous leukemia (AML); FAB M1, M2, M4, M5, M6, or M7
• No AML secondary to chemotherapy, radiation therapy, or toxic agents
• No history of myelodysplastic syndromes
• If possible, patient should be enrolled on protocol RUSH-CYL-9003

--Prior/Concurrent Therapy--

• Biologic therapy: At least 2 weeks since prior interferon; At least 2 weeks since prior hematopoietic growth factors (including erythropoietin)
• Chemotherapy: At least 2 weeks since prior chemotherapy
• Endocrine therapy: At least 2 weeks since prior steroids
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: At least 2 weeks since prior retinoids

--Patient Characteristics--

• Age: 70 and under
• Performance status: 0-3
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin greater than 2.0 mg/dL and no greater than 3.0 mg/dL allowed with 50% reduction in drug doses
• Renal: Creatinine less than 3.0 mg/dL
• Cardiovascular: No overt congestive heart failure; No uncontrollable ventricular arrhythmias; No uncontrollable hypertension; If cardiac ejection fraction is less than 45% of predicted, an echocardiogram and a cardiac consult must be obtained to ascertain cardiac tolerance of anthracycline therapy
• Neurological: No cerebellar dysfunction
• Other: Fever, infection, or other complications of disease allowed; Not pregnant or nursing; Effective contraception required of all fertile patients

Illinois
      Angelo P. Creticos, M.D. Cancer Center, Chicago,  Illinois,  60657,  United States
      Cook County Hospital, Chicago,  Illinois,  60612-9985,  United States
      Rush Cancer Institute, Chicago,  Illinois,  60612,  United States
      Rush-Riverside Cancer Center, Kankakee,  Illinois,  60901,  United States

Study chairs or principal investigators

Harvey D. Preisler,  Study Chair,  Rush Cancer Institute at Rush University Medical Center   

Study ID Numbers:  CDR0000066413; RUSH-AML-9754; NCI-V98-1445; ALZA-RUSH-AML-9754
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003405
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08