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

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003875
• Other study ID #: 1315.00
• Secondary ID: NCI-2011-0043913
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: August 4, 2015
• Start date: November 1998

Study information

• Verified date: August 2015
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Childhood Acute Myeloid Leukemia

Intervention

Drug:
• busulfan
Given PO or IV
• etoposide
Given IV

Biological:
• aldesleukin
Given SC

Procedure:
• peripheral blood stem cell transplantation
Undergo autologous or syngeneic stem cell rescue

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival of patients on busulfan and etoposide followed by stem cell rescue and aldesleukin	Estimated by the method of Kaplan and Meier.	At 3 years	No
Primary	Toxicity associated with high-dose busulfan and etoposide followed by stem cell rescue and aldesleukin	Toxicity is defined as any grade 3 or grade 4 toxicity following high-dose chemotherapy; inability to recover sufficiently by day 100 to start IL-2 therapy; or toxicity during IL-2 therapy of any of the following nature: 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.	Day -7 to day 100	Yes
Secondary	Rate of relapse associated with the regimen	Summarized using a cumulative incidence estimate, with death without relapse considered as a competing risk. This rate will be informally compared to that of alternate regimens to gain an idea of the impact of this regimen on relapse.	Every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter	No