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

May 3, 2017 updated by: Leona Holmberg, Fred Hutchinson Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (chemo, stem cell rescue, interleukin therapy)

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: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Biological: aldesleukin
Given SC
Other Names:
  • Proleukin
  • IL-2
  • recombinant human interleukin-2
  • recombinant interleukin-2
Drug: busulfan
Given PO or IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Procedure: peripheral blood stem cell transplantation
Undergo autologous or syngeneic stem cell rescue
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin
Time Frame: From date of transplant to date of death from any cause, assessed up to 178 months
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
Time Frame: Day -7 of transplant to 100 days post transplant
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
Time Frame: IL-2 administration to one month after completion of IL-2 treatment
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
Time Frame
Proportion of Patients Who Relapsed Associated With the Regimen
Time Frame: From date of transplant to date of death from any cause, assessed up to 178 months
From date of transplant to date of death from any cause, assessed up to 178 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 13, 1998

Primary Completion (Actual)

June 11, 2015

Study Completion (Actual)

June 11, 2015

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

June 5, 2017

Last Update Submitted That Met QC Criteria

May 3, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1315.00 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
  • P30CA015704 (U.S. NIH Grant/Contract)
  • NCI-2011-00439 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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