Auto BMT for Non-M3 AML in 1st Remission in Pts </=60y of Age Using Busulfan/FTBI & VP16 as a Prep R

Study Overview
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Brief Summary
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RATIONALE: Giving chemotherapy before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and/or bone marrow and stored. More chemotherapy and radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy. Giving aldesleukin after transplant may help keep cancer cells from coming back after transplant. PURPOSE: This phase II trial is studying the side effects and how well giving busulfan and etoposide together with total-body irradiation followed by autologous stem cell transplant and aldesleukin works in treating patients with acute myeloid leukemia in first remission.

Detailed Description
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OBJECTIVES: To evaluate the efficacy and toxicity of a preparative regimen comprising busulfan, etoposide, and fractionated total-body irradiation followed by autologous stem cell transplantation and aldesleukin after treatment with consolidation therapy comprising high-dose cytarabine with or without idarubicin in patients with acute myeloid leukemia in first remission. To estimate the long-term disease-free survival of patients treated with this regimen. To further evaluate the effect of prognostic factors (e.g., cytogenetics, WBC at presentation, and number of courses of induction therapy required to achieve remission) on the outcome of autologous stem cell transplantation and targeted busulfan dose. OUTLINE: Consolidation therapy: Patients who received prior consolidation therapy are evaluated to determine the need for additional consolidation therapy. Patients who have not received prior consolidation therapy receive high-dose cytarabine IV over 3 hours every 12 hours on days 1-4 and idarubicin* IV over 5-10 minutes on days 1-3. NOTE: *Patients with good risk cytogenetics t(8;21), inv(16), or t(16;16) or patients who received > 200 mg/m² of anthracycline do not receive idarubicin. Stem cell collection: All patients receive filgrastim (G-CSF) IV or subcutaneously (SC) twice daily beginning 7 days after completion of high-dose cytarabine and continuing until peripheral blood stem cell (PBSC) collection is completed. Patients who do not have an adequate number of PBSCs collected also undergo bone marrow collection. Preparative regimen: Patients receive busulfan IV over 2 hours on days -13 and -11 to -7 and etoposide IV on day -2. Patients also undergo fractionated total-body irradiation on days -6 to -3 for a total of 8-10 fractions. Autologous stem cell transplantation: Patients undergo autologous stem cell transplantation using PBSCs (with or without bone marrow) on day 0. Patients receive G-CSF IV or SC daily beginning on day 5 and continuing until blood counts recover. Interleukin therapy: Within 100 days post-transplantation, patients receive aldesleukin IV continuously on days 1-4 and 9-18. After completion of study treatment, patients are followed periodically.

Official Title
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Autologous Bone Marrow Transplantation for Non-M3 Acute Myeloid Leukemia (AML) in First Remission in Patients </=60 Years of Age Using Busulfan/Fractionated Total Body Irradiation (FTBI) and VP16 as the Preparative Regimen

Conditions
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Leukemia

Intervention / Treatment
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* Biological: aldesleukin
* Biological: filgrastim
* Drug: busulfan
* Drug: cytarabine
* Drug: etoposide
* Drug: idarubicin
* Procedure: autologous hematopoietic stem cell transplantation
* Procedure: bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation
* Radiation: total-body irradiation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of acute myeloid leukemia (AML) FAB types M0-2 and M4-M7 No M3 disease In first complete hematological remission as confirmed by marrow aspiration and biopsy No cytogenetic abnormality in the remission marrow In complete remission for less than 6 months Patients who have been in complete remission for more than 6 months may be eligible upon approval of the principal investigator No prior myeloproliferative disorder (e.g., chronic myeloid leukemia, myelofibrosis, essential thrombocytosis, or polycythemia vera) No prior myelodysplasia or secondary leukemia PATIENT CHARACTERISTICS: FEV_1 > 60% DLCO > 50% Cardiac ejection fraction ≥ 50% Creatinine clearance > 60 mL/min No severe chronic medical or psychological illness that, in the judgement of the principal investigator, would jeopardize the ability of the patient to tolerate aggressive chemotherapy No HIV positivity Not pregnant Negative pregnancy test PRIOR CONCURRENT THERAPY: Prior consolidation therapy allowed No concurrent use the following medications during aldesleukin therapy : Corticosteroids (including blood product pre-meds) Pentoxifylline IV or intrathecal methotrexate IV immunoglobulin Other cytokines or growth factors

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HD ARA-C with or without Idarubicin<br>This study was designed as a single-arm study. Strata were: HD ARA-C w/ Idarubicin, CR<6 months N = 24 patients. HD ARA-C w/ Idarubicin, CR>6 months N=1. HD ARA-C consolidation, CR<6 months N=5. HD ARA-C consolidation, CR>6 months N= 0. | Biological: aldesleukin<br> <br> * Other names: Proleukin;Biological: filgrastim<br> <br> * Other names: Neupogen;Drug: busulfan<br> <br> * Other names: Busulfex IV;Drug: cytarabine<br> <br> * Other names: Cytosar-U;Drug: etoposide<br> <br> * Other names: Etophosphos;Drug: idarubicin<br> <br> * Other names: 4-demethoxydaunorubicin;Procedure: autologous hematopoietic stem cell transplantation<br> <br> Procedure: bone marrow transplantation<br> <br> Procedure: peripheral blood stem cell transplantation<br> <br> Radiation: total-body irradiation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival at 2-Year Post-Transplant | Kaplan-Meier estimates at 2-years post-transplant, with 95% confidence intervals based on logit limit transformation of Greenwood's variance. Outcome is death or relapse, censor is alive in continual complete remission at the date of last clinical disease assessment. | Estimate at 2 years post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival at 2-Year Post-Transplant by Cytogenetic Risk | Kaplan-Meier estimates at 2-years post-transplant, with 95% confidence intervals based on logit limit transformation of Greenwood's variance. Outcome is death or relapse, censor is alive in continual complete remission at the date of last clinical disease assessment. | Kaplan-Meier estimate 2 years post treatment | 

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