High Dose Chemotherapy, Peripheral Stem Cell Transplantation, and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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. Interleukin-2 may stimulate a person's white blood cells to kill leukemia cells. PURPOSE: Phase III trial to study the effectiveness of high-dose combination chemotherapy, peripheral stem cell transplantation, and interleukin-2 in treating patients who have acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Determine relapse free survival of patients with previously untreated de novo or secondary acute myeloid leukemia treated with high dose cytarabine and idarubicin induction, high dose etoposide and cyclophosphamide intensification, filgrastim (G-CSF), melphalan, radiotherapy, autologous peripheral blood stem cell (PBSC) transplantation, and interleukin-2. Correlate remission rate and relapse free survival with multidrug resistance phenotype in patients treated with this regimen. Determine stem cell content and presence of cells with leukemia specific markers in PBSC harvested following high dose etoposide and cyclophosphamide intensification. Correlate NK cell expansion (an increase in both proportion and absolute number) during interleukin-2 therapy following autologous PBSC transplantation with disease free survival. OUTLINE: Induction Patients receive cytarabine IV over 1 hour every 12 hours for 6 days and idarubicin IV over 30 minutes following third, fifth, and seventh doses of cytarabine. Beginning 12 hours after the last dose of cytarabine, patients receive filgrastim (G-CSF) subcutaneously (SQ) each day until blood counts recover. Intensification Patients receive etoposide IV over 34.3 hours followed 1 hour later by cyclophosphamide IV over 2 hours for 3 days. Beginning 24 hours after the last dose of cyclophosphamide, patients receive G-CSF SQ each day until blood counts recover. Peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells. Patients receive melphalan IV over 1 hour on day -4 followed by total body irradiation on days -3, -2, and -1. PBSC are reinfused on day 0. When blood counts recover, patients receive high dose interleukin-2 SQ on days 1-10 followed by low dose interleukin-2 SQ on days 11-13. Interleukin-2 treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with immunologic response to 6 courses of interleukin-2 treatment may continue for 6 additional courses. PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study over 5 years.

Official Title
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High-Dose Cytarabine and Idarubicin Induction, High Dose Etoposide and Cyclophosphamide Intensification, Autologous Stem Cell Transplantation and Interleukin-2 Immune Modulation in Previously Untreated De Novo and Secondary Adult Myeloid Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Biological: aldesleukin
* Biological: filgrastim
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: etoposide
* Drug: idarubicin
* Drug: melphalan
* Procedure: peripheral blood stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven de novo or secondary acute myeloid leukemia with a classification of M0-M2 or M4-M7 No classification of M3 No promyelocytic leukemia Prior medical conditions allowed: Myelodysplastic syndromes Aplastic anemia Paroxysmal nocturnal hemoglobinuria Myeloproliferative disorders except Philadelphia chromosome positive chronic myelogenous leukemia PATIENT CHARACTERISTICS: Age: Over 25 Performance status: Not specified Life expectancy: At least 4 weeks Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times normal SGOT no greater than 2 times normal Alkaline phosphatase no greater than 2 times normal Renal: Creatinine no greater than 1.5 times normal Cardiovascular: Ejection fraction at least 45% No severe cardiovascular disease including myocardial infarction within past 6 months, uncontrolled symptomatic congestive heart failure, angina pectoris, or multifocal cardiac arrhythmias Other: No uncontrolled diabetes mellitus No other active malignancy No hypersensitivity to E. coli derived drug preparations PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for acute leukemia except hydroxyurea Prior chemotherapy allowed for other malignancy or other medical condition Endocrine therapy: Not specified Radiotherapy: Prior radiotherapy allowed for other malignancy or other medical condition Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 25 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|IV|
|Biological: filgrastim|IV|
|Drug: cyclophosphamide|IV|
|Drug: cytarabine|IV|
|Drug: etoposide|IV|
|Drug: idarubicin|IV|
|Drug: melphalan|IV|
|Procedure: peripheral blood stem cell transplantation|IV|
|Radiation: radiation therapy|delivered to the cancer cells|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the efficacy of 4-6 h and 18-24 h, 20% ALA applications on superficial and nodular epidermally-derived lesions using ca633 nm laser irradiation. | To determine the efficacy of 4-6 h and 18-24 h, 20% ALA applications on superficial and nodular epidermally-derived lesions using ca633 nm laser irradiation. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult acute monoblastic leukemia and acute monocytic leukemia (M5), adult acute erythroid leukemia (M6), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute megakaryoblastic leukemia (M7), secondary acute myeloid leukemia, adult acute minimally differentiated myeloid leukemia (M0), untreated adult acute myeloid leukemia