S0301 Cyclosporine, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cyclosporine, daunorubicin, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving cyclosporine together with daunorubicin and cytarabine works in treating older patients with untreated acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Determine the safety and efficacy of cyclosporine, daunorubicin, and cytarabine in older patients with previously untreated acute myeloid leukemia. Determine the frequency and severity of toxic effects of this regimen in these patients. Determine, preliminarily, the frequency and prognostic significance of functional and phenotypic P-glycoprotein expression and cytogenetics in patients treated with this regimen. Determine, preliminarily, the pharmacokinetic characteristics of this regimen in these patients. OUTLINE: This is a multicenter study. Induction therapy: Patients receive cyclosporine IV and daunorubicin IV continuously on days 1-3 and cytarabine IV continuously on days 1-7. Patients who achieve complete response (CR) after chemotherapy receive filgrastim (G-CSF) or sargramostim (GM-CSF) IV or subcutaneously beginning on day 15 or 20 and continuing until blood counts recover. Patients who maintain CR after 2 courses of induction therapy proceed to consolidation therapy. Consolidation therapy: Patients receive treatment as in induction therapy with cyclosporine and daunorubicin on days 1-2 and cytarabine on days 1-5. Patients achieving CR receive an additional course of chemotherapy beginning at least 14 days after completion of the first course of cytarabine. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years. PROJECTED ACCRUAL: A total of 25-64 patients will be accrued for this study within 13 months.

Official Title
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A Phase II Study Of Induction With Daunorubicin, Cytarabine, And Cyclosporine All By Continuous IV Infusion For Previously Untreated Non-M3 Acute Myeloid Leukemia (AML) In Patients Of Age 56 Or Older

Conditions
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Leukemia

Intervention / Treatment
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* Biological: filgrastim
* Biological: sargramostim
* Drug: cyclosporine
* Drug: cytarabine
* Drug: daunorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Morphologically confirmed acute myeloid leukemia (AML) Differential diagnosis of AML based on FAB classification system M0-M7 (No M3) No blastic transformation of chronic myelogenous leukemia Must be currently registered on protocols SWOG-9007 and SWOG-S9910 PATIENT CHARACTERISTICS: Age 56 and over Performance status Zubrod 0-3 (for patients 56 to 60 years of age) OR Zubrod 0-2 (for patients 61 to 70 years of age) OR Zubrod 0-1 (for patients 71 years of age and over) Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin no greater than 2 times upper limit of normal (ULN) unless elevated unconjugated hyperbilirubinemia is secondary to Gilbert's syndrome or hemolysis and not to liver dysfunction AST and/or ALT no greater than 4 times ULN Renal Creatinine no greater than 1.5 times ULN AND/OR Creatinine clearance greater than 40 mL/min Cardiovascular Left ventricular function normal Ejection fraction at least 50% by MUGA or echocardiogram No unstable cardiac arrhythmias No unstable angina Other Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent pegfilgrastim Chemotherapy At least 30 days since prior low-dose cytarabine (less than 100 mg/m^2/day) for myelodysplastic syndromes and recovered Prior hydroxyurea to control high cell counts allowed No prior systemic chemotherapy for acute leukemia Concurrent single-dose intrathecal chemotherapy allowed Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Minimum Age: 56 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|5 mcg/kg/d IV or SC starting apx day 15|
|Biological: sargramostim|250 mcg/kg/d IV or SC starting apx day 15|
|Drug: cyclosporine|ind: 6 mg/kg load IV over 2 hrs days 0-2 followed by 16 mg/dg/d continuous IV days 2-74 consol: 6 mg/kg load IV over 2 hrs days 0-2 followed by 16 mg/dg/d continuous IV days 2-50|
|Drug: cytarabine|ind: 200 mg/m2/d cont IV days 2-74|
|Drug: daunorubicin hydrochloride|ind: 45 mg/m2/d cont IV days 2-74|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission (CR) |  | After induction therapy is completed | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult acute monocytic leukemia (M5b), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), untreated adult acute myeloid leukemia, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult pure erythroid leukemia (M6b), adult erythroleukemia (M6a)