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Combination Chemotherapy, Interleukin-2, and Peripheral Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2008 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: December 10, 1999
Last updated: December 22, 2009
Last verified: April 2008

December 10, 1999
December 22, 2009
September 1999
January 2008   (final data collection date for primary outcome measure)
  • Duration of overall survival and disease-free survival after first randomization [ Designated as safety issue: No ]
  • Duration of overall survival and disease-free survival after second randomization [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00004128 on Archive Site
  • Response after induction and consolidation [ Designated as safety issue: No ]
  • Toxicity measured by Cancer and Leukemia Group B (CALGB) CTCAE v3.0 after induction and consolidation [ Designated as safety issue: Yes ]
  • Disease-free survival after complete remission (CR) [ Designated as safety issue: No ]
  • Disease-free interval from CR [ Designated as safety issue: No ]
  • Time to death in CR [ Designated as safety issue: No ]
  • Peripheral stem cell harvest after consolidation [ Designated as safety issue: No ]
  • Rate of completion of autologous peripheral blood stem cell transplantation (auto-PBSCT) and allogeneic stem cell transplantation (allo-SCT) [ Designated as safety issue: No ]
Not Provided
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Combination Chemotherapy, Interleukin-2, and Peripheral Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia
The Value of High Dose Versus Standard Dose ARA-C During Induction and of IL-2 After Intensive Consolidation/Autologous Stem Cell Transplantation in Patients (Age 15-60 Years) With Acute Myelogenous Leukemia. A Randomized Phase II Trial of the EORTC and the GIMEMA-ALWP

RATIONALE: Giving combination chemotherapy before a peripheral blood 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 or bone marrow and stored. More chemotherapy or radiation therapy is given 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. Interleukin-2 may stimulate the patient's white blood cells to kill cancer cells.

PURPOSE: This randomized phase III trial is studying two different regimens of combination chemotherapy, interleukin-2, and peripheral stem cell transplant and comparing them to see how well they work in treating patients with acute myeloid leukemia.


  • Compare the overall survival rate in patients with acute myeloid leukemia treated with high-dose versus standard-dose cytarabine during induction.
  • Compare the disease-free survival rate in patients treated with or without interleukin-2 following consolidation and autologous peripheral blood stem cell or bone marrow transplantation.
  • Compare the feasibility of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients in the first randomization are stratified according to center, WBC (no greater than 25,000/mm^3 vs 25,000-99,000/mm^3 vs at least 100,000/mm^3), age (15 to 45 vs 46 to 60), and performance status (0-1 vs 2 vs 3). Patients in the second randomization are stratified according to center, first treatment arm (I vs II), number of induction courses to reach complete remission (CR), cytogenic/molecular genetic group at diagnosis (low vs high vs intermediate vs unknown), and autologous peripheral blood stem cell (PBSC) transplantation planned after consolidation (yes vs no).

First randomization

  • Induction: Patients are randomized to 1 of 2 treatment arms:

    • Arm I: Patients receive standard-dose cytarabine IV over 24 hours on days 1-10, etoposide IV over 1 hour on days 1-5, and daunorubicin IV over 5 minutes on days 1, 3, and 5.
    • Arm II: Patients receive etoposide and daunorubicin as in arm I and high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, 5, and 7.
  • Consolidation: When CR is reached, patients receive intermediate-dose cytarabine IV over 2 hours every 12 hours on days 1-6 and daunorubicin IV over 5 minutes prior to cytarabine on days 4, 5, and 6.
  • Harvest: Patients who achieve CR and are ineligible for allogeneic PBSC transplantation receive filgrastim (G-CSF) subcutaneously (SQ) every 12 hours beginning 20 days after starting consolidation treatment and continuing until autologous PBSC are harvested. Autologous bone marrow is collected from patients with insufficient PBSC. Allogeneic PBSC are harvested for patients who have an HLA identical donor. Allogeneic bone marrow is harvested for high risk patients (under age 40) who have an unrelated bone marrow donor.
  • Transplant preparative chemotherapy: It is recommended that patients receive cyclophosphamide on 2 consecutive days and total body irradiation on 3 days OR busulfan on days -8, -7, -6, and -5 followed by cyclophosphamide on days -4 and -3.
  • Transplantation: PBSC or bone marrow is infused on day 0.

Second randomization

  • Patients who achieve CR with full hematologic recovery but have no HLA identical donor are randomized to 1 of 2 treatment arms no earlier than day 22 after stem cell infusion.

    • Arm I: Patients receive interleukin-2 SQ once daily for 5 days. Treatment repeats every 4 weeks for 1 year in the absence of disease progression or unacceptable toxicity.
    • Arm II: Patients receive no further treatment. Patients are followed at 1, 4, and 13 months, then every 4 months for 3 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 2,000 patients (1,000 per treatment arm) will be accrued for the first randomization and a total of 577 patients (288 per treatment arm) will be accrued for the second randomization of this study.

Phase 3
Allocation: Randomized
Primary Purpose: Treatment
  • Biological: aldesleukin
  • Biological: filgrastim
  • Drug: busulfan
  • Drug: cyclophosphamide
  • Drug: cytarabine
  • Drug: daunorubicin hydrochloride
  • Drug: etoposide
  • Procedure: autologous bone marrow transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Active, not recruiting
Not Provided
January 2008   (final data collection date for primary outcome measure)


  • First randomization:

    • Untreated newly diagnosed acute myeloid leukemia (AML)
    • At least 30% blasts in bone marrow
    • All cytological types of AML except acute promyelocytic leukemia (M3)
    • No blast crisis of chronic myelogenous leukemia
    • No leukemias supervening after other myeloproliferative disease
    • No leukemias supervening after overt myelodysplastic disorders (e.g., refractory anemia with excess blasts) for more than 6 months duration
  • Second randomization:

    • Must have achieved complete remission with full hematologic recovery following consolidation treatment
    • No HLA identical family donor
    • Not eligible for allograft
    • No high risk patient (under age 40) for whom an unrelated bone marrow donor has been found within 8 weeks of beginning consolidation treatment



  • 15 to 60

Performance status:

  • WHO 0-3 (first randomization)
  • WHO 0-2 (second randomization)

Life expectancy:

  • Not specified


  • Not specified


  • Bilirubin no greater than 3 times upper limit of normal (ULN)


  • Creatinine no greater than 3 times ULN


  • No severe heart failure requiring diuretics
  • Ejection fraction at least 50%


  • First randomization:

    • No other progressive malignant disease except the following:

      • Secondary acute leukemias following curatively treated Hodgkin's disease (even if treated with anthracyclines)
      • Other curatively treated malignancies
      • Secondary leukemias following other exposure to alkylating agents or radiotherapy for other reason
    • No uncontrolled infection
    • No severe concurrent neurologic or psychiatric disease
    • No psychological, familial, sociological, or geographical condition that could preclude compliance
  • Second randomization:

    • No nonmalignant systemic illness that would increase risk of participation in study
    • No uncontrolled infection
    • No other progressive malignant disease


Biologic therapy:

  • Not specified


  • No prior chemotherapy for AML except hydroxyurea
  • Less than 7 days of prior hydroxyurea

Endocrine therapy:

  • No more than 7 days of prior corticosteroid therapy for AML


  • No prior radiotherapy for AML


  • Not specified
15 Years to 60 Years
Contact information is only displayed when the study is recruiting subjects
Not Provided
CDR0000067356, EORTC-06991, GIMEMA-EORTC-06991
Not Provided
Not Provided
European Organisation for Research and Treatment of Cancer - EORTC
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigator: Roel Willemze, MD, PhD Leiden University Medical Center
Study Chair: Giovanna Meloni, MD University La Sapienza
National Cancer Institute (NCI)
April 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP