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

NCT00003875 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 1315.00NCI-2011-00439P30CA015704
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin

  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

  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

  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 Outcomes (1)

• Proportion of Patients Who Relapsed Associated With the Regimen

  From date of transplant to date of death from any cause, assessed up to 178 months

Study Arms (1)

Treatment (chemo, stem cell rescue, interleukin therapy)

EXPERIMENTAL

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; Drug: etoposide; Biological: aldesleukin; Procedure: peripheral blood stem cell transplantation

Interventions

busulfan DRUG

Given PO or IV

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

Treatment (chemo, stem cell rescue, interleukin therapy)

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

Treatment (chemo, stem cell rescue, interleukin therapy)

aldesleukin BIOLOGICAL

Given SC

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Treatment (chemo, stem cell rescue, interleukin therapy)

peripheral blood stem cell transplantation PROCEDURE

Undergo autologous or syngeneic stem cell rescue

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (chemo, stem cell rescue, interleukin therapy)

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 34400362 DERIVED

MeSH Terms

Conditions

Congenital Abnormalities; Leukemia, Myeloid, Acute

Interventions

Busulfan; Etoposide; aldesleukin; Interleukin-2; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Leona A. Holmberg
• Organization: Fred Hutchinson Cancer Research Center

lholmber@fredhutch.org

206-667-6447

Study Officials

• Leona Holmberg

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: October 13, 1998
• Primary Completion: June 11, 2015
• Study Completion: June 11, 2015
• Last Updated: June 5, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)