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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

Primary Purpose

Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
busulfan
etoposide
aldesleukin
peripheral blood stem cell transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Myeloid Leukemia in Remission

Eligibility Criteria

undefined - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemo, stem cell rescue, interleukin therapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin
Estimated by the method of Kaplan and Meier.
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.
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.

Secondary Outcome Measures

Proportion of Patients Who Relapsed Associated With the Regimen

Full Information

First Posted
November 1, 1999
Last Updated
May 3, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003875
Brief Title
Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
October 13, 1998 (Actual)
Primary Completion Date
June 11, 2015 (Actual)
Study Completion Date
June 11, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemo, stem cell rescue, interleukin therapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
busulfan
Other Intervention Name(s)
BSF, BU, Misulfan, Mitosan, Myeloleukon
Intervention Description
Given PO or IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
aldesleukin
Other Intervention Name(s)
IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Intervention Description
Given SC
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo autologous or syngeneic stem cell rescue
Primary Outcome Measure Information:
Title
Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin
Description
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
Title
Toxicity Associated With High-dose Busulfan and Etoposide Followed by Stem Cell Rescue
Description
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
Title
Toxicity Associated With Aldesleukin Treatment After Stem Cell Rescue
Description
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 Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leona Holmberg
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34400362
Citation
Miller HN, Berger MB, Askew S, Kay MC, Hopkins CM, Iragavarapu MS, de Leon M, Freed M, Barnes CN, Yang Q, Tyson CC, Svetkey LP, Bennett GG, Steinberg DM. The Nourish Protocol: A digital health randomized controlled trial to promote the DASH eating pattern among adults with hypertension. Contemp Clin Trials. 2021 Oct;109:106539. doi: 10.1016/j.cct.2021.106539. Epub 2021 Aug 13.
Results Reference
derived

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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

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