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

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	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

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	30 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Actual Study Start Date :	October 13, 1998
Actual Primary Completion Date :	June 11, 2015
Actual Study Completion Date :	June 11, 2015

Arms and Interventions

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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: 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

Outcome Measures

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Primary Outcome Measures :

1. 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.
2. 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.
3. 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.

Secondary Outcome Measures :

1. 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 ]

Eligibility Criteria

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Ages Eligible for Study:	up to 65 Years (Child, Adult)
Sexes Eligible for Study:	All
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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Leona Holmberg, Principal Investigator, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00003875 History of Changes
Other Study ID Numbers:	1315.00; NCI-2011-00439 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 1315.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium ); P30CA015704 ( U.S. NIH Grant/Contract )
First Posted:	January 27, 2003
Results First Posted:	June 5, 2017
Last Update Posted:	June 5, 2017
Last Verified:	May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

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