Combination Chemotherapy, Interleukin-2, and Peripheral Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia
Recruitment status was Active, not recruiting
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.
Drug: daunorubicin hydrochloride
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||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|
- 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 ]
- 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 ]
|Study Start Date:||September 1999|
|Estimated Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
- 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).
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004128
|Investigator:||Roel Willemze, MD, PhD||Leiden University Medical Center|
|Study Chair:||Giovanna Meloni, MD||University La Sapienza|