Clinical trial NCT00003875: 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
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 30
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin
timeFrame: From date of transplant to date of death from any cause, assessed up to 178 months
measure: Toxicity Associated With High-dose Busulfan and Etoposide Followed by Stem Cell Rescue
timeFrame: Day -7 of transplant to 100 days post transplant
measure: Toxicity Associated With Aldesleukin Treatment After Stem Cell Rescue
timeFrame: IL-2 administration to one month after completion of IL-2 treatment
Secondary outcomes:
measure: Proportion of Patients Who Relapsed Associated With the Regimen
timeFrame: From date of transplant to date of death from any cause, assessed up to 178 months
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Leona Holmberg
role: PRINCIPAL_INVESTIGATOR
References:
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.