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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:
Fred Hutchinson Cancer Research Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Leona Holmberg, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00003875
First received: November 1, 1999
Last updated: May 3, 2017
Last verified: May 2017
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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: | 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 |
Resource links provided by NLM:
Genetics Home Reference related topics:
core binding factor acute myeloid leukemia
cytogenetically normal acute myeloid leukemia
familial acute myeloid leukemia with mutated CEBPA
Genetic and Rare Diseases Information Center resources:
Myeloid Leukemia
Acute Myeloid Leukemia
Acute Non Lymphoblastic Leukemia
U.S. FDA Resources
Further study details as provided by Leona Holmberg, 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: From date of transplant to date of death from any cause, assessed up to 178 months ]Estimated by the method of Kaplan and Meier.
- 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.
- 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:
- 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 ]
| Enrollment: | 30 |
| Actual Study Start Date: | October 13, 1998 |
| Study Completion Date: | June 11, 2015 |
| Primary Completion Date: | June 11, 2015 (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:
Drug: etoposide
Given IV
Other Names:
Biological: aldesleukin
Given SC
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo autologous or syngeneic stem cell rescue
Other Names:
|
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) |
| 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
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
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: | 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 ) |
| Study First Received: | November 1, 1999 |
| Results First Received: | March 18, 2017 |
| Last Updated: | May 3, 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 |
ClinicalTrials.gov processed this record on September 21, 2017