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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00534469
First received: September 20, 2007
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Leukemia
Biological: aldesleukin
Biological: filgrastim
Drug: busulfan
Drug: cytarabine
Drug: etoposide
Drug: idarubicin
Procedure: autologous hematopoietic stem cell transplantation
Procedure: bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Efficacy of preparative therapy as measured by 2- and 5-year disease-free survival [ Designated as safety issue: No ]
  • Toxicity of preparative therapy [ Designated as safety issue: Yes ]
  • Feasibility of administration and ability to tolerate aldesleukin after transplantation [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: January 2000
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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: NCT00534469

Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: Anthony S. Stein, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00534469     History of Changes
Other Study ID Numbers: 99040, P30CA033572, CHNMC-99040, CDR0000564772
Study First Received: September 20, 2007
Last Updated: December 16, 2013
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute basophilic leukemia
adult acute eosinophilic leukemia
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Busulfan
Cytarabine
Etoposide phosphate
Aldesleukin
Etoposide
Idarubicin
Lenograstim
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014