Busulfan, Etoposide, and Total-Body Irradiation Followed by Autologous Stem Cell Transplant and Aldesleukin in Treating Patients With Acute Myeloid Leukemia in First Remission

Sponsor
City of Hope Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00534469
Collaborator
National Cancer Institute (NCI) (NIH)
50
2
274.7

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and/or bone marrow and stored. More chemotherapy and radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy. Giving aldesleukin after transplant may help keep cancer cells from coming back after transplant.

PURPOSE: This phase II trial is studying the side effects and how well giving busulfan and etoposide together with total-body irradiation followed by autologous stem cell transplant and aldesleukin works in treating patients with acute myeloid leukemia in first remission.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OBJECTIVES:
  • To evaluate the efficacy and toxicity of a preparative regimen comprising busulfan, etoposide, and fractionated total-body irradiation followed by autologous stem cell transplantation and aldesleukin after treatment with consolidation therapy comprising high-dose cytarabine with or without idarubicin in patients with acute myeloid leukemia in first remission.

  • To estimate the long-term disease-free survival of patients treated with this regimen.

  • To further evaluate the effect of prognostic factors (e.g., cytogenetics, WBC at presentation, and number of courses of induction therapy required to achieve remission) on the outcome of autologous stem cell transplantation and targeted busulfan dose.

OUTLINE:
  • Consolidation therapy: Patients who received prior consolidation therapy are evaluated to determine the need for additional consolidation therapy. Patients who have not received prior consolidation therapy receive high-dose cytarabine IV over 3 hours every 12 hours on days 1-4 and idarubicin* IV over 5-10 minutes on days 1-3.

NOTE: *Patients with good risk cytogenetics t(8;21), inv(16), or t(16;16) or patients who received > 200 mg/m² of anthracycline do not receive idarubicin.

  • Stem cell collection: All patients receive filgrastim (G-CSF) IV or subcutaneously (SC) twice daily beginning 7 days after completion of high-dose cytarabine and continuing until peripheral blood stem cell (PBSC) collection is completed. Patients who do not have an adequate number of PBSCs collected also undergo bone marrow collection.

  • Preparative regimen: Patients receive busulfan IV over 2 hours on days -13 and -11 to -7 and etoposide IV on day -2. Patients also undergo fractionated total-body irradiation on days -6 to -3 for a total of 8-10 fractions.

  • Autologous stem cell transplantation: Patients undergo autologous stem cell transplantation using PBSCs (with or without bone marrow) on day 0. Patients receive G-CSF IV or SC daily beginning on day 5 and continuing until blood counts recover.

  • Interleukin therapy: Within 100 days post-transplantation, patients receive aldesleukin IV continuously on days 1-4 and 9-18.

After completion of study treatment, patients are followed periodically.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Autologous Bone Marrow Transplantation for Non-M3 Acute Myeloid Leukemia (AML) in First Remission in Patients </=60 Years of Age Using Busulfan/Fractionated Total Body Irradiation (FTBI) and VP16 as the Preparative Regimen
Actual Study Start Date :
Feb 8, 2000
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: HD ARA-C with Idarubicin

HD ARA-C with Idarubicin Consolidation, Busulfan/FTBI/VP16/PSC/BMT

Biological: aldesleukin

Biological: filgrastim

Drug: busulfan

Drug: cytarabine

Drug: etoposide

Drug: idarubicin

Procedure: autologous hematopoietic stem cell transplantation

Procedure: peripheral blood stem cell transplantation

Radiation: total-body irradiation

Active Comparator: HD ARA-C without Idarubicin

HD ARA-C Consolidation, Busulfan/FTBI/VP16/PSC/BMT

Biological: aldesleukin

Biological: filgrastim

Drug: busulfan

Drug: cytarabine

Drug: etoposide

Procedure: autologous hematopoietic stem cell transplantation

Procedure: bone marrow transplantation

Procedure: peripheral blood stem cell transplantation

Radiation: total-body irradiation

Outcome Measures

Primary Outcome Measures

  1. Efficacy of preparative therapy as measured by 2- and 5-year disease-free survival [5 years post treatment]

  2. Toxicity of preparative therapy [Day 100 post treatment]

  3. Feasibility of administration and ability to tolerate aldesleukin after transplantation [5 years post treatment]

Secondary Outcome Measures

  1. Effect of cytogenetics, WBC at presentation, targeted busulfan dose, and number of courses of induction therapy required to achieve remission on possible prognostic factors for relapse, disease-free survival, and overall survival [5 years post treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:
16 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
DISEASE CHARACTERISTICS:
  • Diagnosis of acute myeloid leukemia (AML)

  • FAB types M0-2 and M4-M7

  • No M3 disease

  • In first complete hematological remission as confirmed by marrow aspiration and biopsy

  • No cytogenetic abnormality in the remission marrow

  • In complete remission for less than 6 months

  • Patients who have been in complete remission for more than 6 months may be eligible upon approval of the principal investigator

  • No prior myeloproliferative disorder (e.g., chronic myeloid leukemia, myelofibrosis, essential thrombocytosis, or polycythemia vera)

  • No prior myelodysplasia or secondary leukemia

PATIENT CHARACTERISTICS:
  • FEV_1 > 60%

  • DLCO > 50%

  • Cardiac ejection fraction ≥ 50%

  • Creatinine clearance > 60 mL/min

  • No severe chronic medical or psychological illness that, in the judgement of the principal investigator, would jeopardize the ability of the patient to tolerate aggressive chemotherapy

  • No HIV positivity

  • Not pregnant

  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:
  • Prior consolidation therapy allowed

  • No concurrent use the following medications during aldesleukin therapy :

  • Corticosteroids (including blood product "pre-meds")

  • Pentoxifylline

  • IV or intrathecal methotrexate

  • IV immunoglobulin

  • Other cytokines or growth factors

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • City of Hope Medical Center
  • National Cancer Institute (NCI)

Investigators

  • Study Chair: Anthony S. Stein, MD, City of Hope Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00534469
Other Study ID Numbers:
  • 99040
  • P30CA033572
  • CHNMC-99040
  • CDR0000564772
First Posted:
Sep 24, 2007
Last Update Posted:
Feb 21, 2022
Last Verified:
Feb 1, 2022

Study Results

No Results Posted as of Feb 21, 2022