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

Fred Hutchinson Cancer Center30 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin

Estimated by the method of Kaplan and Meier.

Time frame: 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.

Time frame: 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.

Time frame: IL-2 administration to one month after completion of IL-2 treatment

Secondary Outcomes

Proportion of Patients Who Relapsed Associated With the Regimen