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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Unknown status

CT.gov ID

NCT00004128

Collaborator

Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)

2,000

Enrollment

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	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	Phase 3

Detailed Description

OBJECTIVES:

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2000 participants

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

Study Start Date :

Sep 1, 1999

Anticipated Primary Completion Date :

Jan 1, 2008

Outcome Measures

Primary Outcome Measures

Duration of overall survival and disease-free survival after first randomization []
Duration of overall survival and disease-free survival after second randomization []

Secondary Outcome Measures

Response after induction and consolidation []
Toxicity measured by Cancer and Leukemia Group B (CALGB) CTCAE v3.0 after induction and consolidation []
Disease-free survival after complete remission (CR) []
Disease-free interval from CR []
Time to death in CR []
Peripheral stem cell harvest after consolidation []
Rate of completion of autologous peripheral blood stem cell transplantation (auto-PBSCT) and allogeneic stem cell transplantation (allo-SCT) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age:

15 to 60

Performance status:

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

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

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

Renal:

Creatinine no greater than 3 times ULN

Cardiovascular:

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

Other:

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