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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00003875
First received: November 1, 1999
Last updated: August 4, 2015
Last verified: August 2015
History of Changes
  Purpose
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.

Condition Intervention Phase
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
 Drug: busulfan
Drug: etoposide
Biological: aldesleukin
Procedure: peripheral blood stem cell transplantation
 Phase 2

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Overall survival of patients on busulfan and etoposide followed by stem cell rescue and aldesleukin [ Time Frame: At 3 years ] [ Designated as safety issue: No ]
    Estimated by the method of Kaplan and Meier.

  • Toxicity associated with high-dose busulfan and etoposide followed by stem cell rescue and aldesleukin [ Time Frame: Day -7 to day 100 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Rate of relapse associated with the regimen [ Time Frame: Every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter ] [ Designated as safety issue: No ]
    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.
Enrollment: 62
Study Start Date: November 1998
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: busulfan
Given PO or IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Biological: aldesleukin
Given SC
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
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

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.

  Eligibility
Ages Eligible for Study:   up to 65 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003875

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Leona Holmberg Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00003875     History of Changes
Other Study ID Numbers: 1315.00  NCI-2011-00439  1315.00  P30CA015704 
Study First Received: November 1, 1999
Last Updated: August 4, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Aldesleukin
Etoposide phosphate
Interleukin-2
Etoposide
Busulfan
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
 Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents, Alkylating
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 26, 2016