Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This phase II trial studies the side effects and how well giving busulfan and etoposide followed by peripheral blood stem cell transplant (PBSCT) and low-dose aldesleukin works in treating patients with acute myeloid leukemia (AML). Drugs used in chemotherapy, such as busulfan and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A PBSCT may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more cancer cells are killed. Aldesleukin may stimulate the white blood cells to kill cancer cells. Giving busulfan and etoposide together followed by PBSCT and aldesleukin may be an effective treatment for AML.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the toxicity and overall survival of high dose Bu (busulfan)/VP-16 (etoposide) followed by post-transplant low-dose interleukin (IL)-2 (aldesleukin) in patients with AML. SECONDARY OBJECTIVES: I. To estimate the rate of relapse associated with this regimen. OUTLINE: PREPARATIVE REGIMEN: Patients receive busulfan intravenously (IV) over 2 hours or orally (PO) every 6 hours on days -7 to -4 and etoposide IV on day -3. STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0. POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin subcutaneously (SC) daily for 12 weeks. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Official Title
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Treatment of Acute Myelogenous Leukemia With Busulfan and Etoposide Followed by Autologous or Syngeneic Stem Cell Rescue and Low-Dose Interleukin 2 (IL-2) Immunotherapy

Conditions
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Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Childhood Acute Myeloid Leukemia in Remission, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: busulfan
* Drug: etoposide
* Biological: aldesleukin
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must have AML that falls into one of the following categories: AML in 1st complete remission (CR) with intermediate or high risk of relapse following conventional therapy; at least, one of the following features is needed: Patient required more than one cycle of induction to achieve first CR White blood cell count (WBC) > 100,000/mm^3 at diagnosis Any of the following cytogenetic abnormalities: inv (3), t(3:3), del (5q) or -5, 11q23, del(7q) or -7, del (20q) or -20, abnormal 12p, +11 or t8 Any other abnormalities or combination of abnormalities which would predict intermediate or high risk of relapse AML beyond first CR Any patient with an identical twin donor who also meets the criteria above Patients with AML in 1st CR should receive at least two cycles of consolidation chemotherapy prior to mobilization and transplant Patients must have an adequate number of stem cells previously collected (i.e., > 2 x 10^8 total nucleated cell [TNC] of bone marrow [BM]/kg or 4 x 10^6 [CD]34+ PBSC/kg, unless approved otherwise by Dr. Holmberg); prior to stem cell collection patients must be documented to be in remission and to have received two cycles of consolidation therapy after induction therapy Pre-Study tests have been performed Patient must sign an institutional review board (IRB) approved informed consent, conforming with federal and institutional guidelines Exclusion Criteria: Patients with good risk AML defined by cytogenetic evaluation with these abnormalities: inversion 16 or t8;21 Patient's life expectancy is severely limited by diseases other than AML Patient is human immunodeficiency virus (HIV) seropositive Patient is pregnant Patient's creatinine > 2.0 mg/dl Patient's total bilirubin > 2.0 mg/dl (unless Gilbert's disease) Or serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) >= 2.5 x upper limit of normal (ULN) not due to leukemia Patient has a history of congestive heart failure, uncontrolled arrhythmias or left ventricular ejection fraction (LVEF) < 50% Patient has an unrelated human leukocyte antigen (HLA) matched donor and is eligible for a higher priority Fred Hutchinson Cancer Research Center (FHCRC) protocol (for FHCRC patients only) Patient has an HLA matched or one antigen mismatch family donor available Patients with a significant active infection that precludes transplant Patients with a Karnofsky Performance Score less than 70

Ages Eligible for Study
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Maximum Age: 65 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: Treatment (chemo, stem cell rescue, interleukin therapy)<br>PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3. STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0. POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks. | Drug: busulfan<br>* Given PO or IV<br>* Other names: Myeloleukon;Drug: etoposide<br>* Given IV<br>* Other names: VP-16-213;Biological: aldesleukin<br>* Given SC<br>* Other names: recombinant interleukin-2;Procedure: peripheral blood stem cell transplantation<br>* Undergo autologous or syngeneic stem cell rescue<br>* Other names: transplantation, peripheral blood stem cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin | Estimated by the method of Kaplan and Meier. | From date of transplant to date of death from any cause, assessed up to 178 months | 
| Toxicity Associated With High-dose Busulfan and Etoposide Followed by Stem Cell Rescue | Toxicity is defined as any grade 3 or grade 4 toxicity per the Bearman toxicity grading criteria following Busulfan and Etoposide high-dose chemotherapy, stem cell transplant, and the inability to recover sufficiently by day 100 to start IL-2 therapy. | Day -7 of transplant to 100 days post transplant | 
| Toxicity Associated With Aldesleukin Treatment After Stem Cell Rescue | Toxicity during IL-2 therapy of any of the following per NCI Common Toxicity version 3: grade 2, 3, 4, or 5 CNS (except grade 0-3 malaise, fatigue, anxiety and depression) toxicity; grade 3, 4, or 5 non-CNS or non-hematologic toxicity; any grade 4 or 5 hematologic toxicity. | IL-2 administration to one month after completion of IL-2 treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Relapsed Associated With the Regimen |  | From date of transplant to date of death from any cause, assessed up to 178 months |