Combination Chemotherapy Plus PSC 833 Followed by Interleukin-2 in Treating Patients With Acute Myelogenous Leukemia
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT00002925
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Some cancers may become resistant to chemotherapy drugs. Combining PSC 833 with chemotherapy may reduce resistance to the drugs and allow the cancer cells to be killed. Interleukin-2 may stimulate a person's white blood cells to kill leukemia cells.
PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus PSC 833 followed by additional chemotherapy or peripheral stem cell transplantation and interleukin-2 in treating patients with untreated acute myelogenous leukemia.
- Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of daunorubicin when used in combination with etoposide, cytarabine, and PSC 833 (ADEP), and in combination with etoposide and cytarabine (ADE) in previously untreated patients with acute myelogenous leukemia who are less than 60 years. II. Determine the MTD of etoposide when used in combination with a constant dose of daunorubicin and cytarabine (ADE) in these patients. III. Determine the feasibility and toxic effects of administering postremission therapy in a risk adapted fashion, such that patients with favorable cytogenetic findings receive three intensifications with high dose cytarabine (HiDAC), while average to poor risk patients receive HiDAC/etoposide/filgrastim (G-CSF) for consolidation therapy and stem cell mobilization followed by peripheral stem cell (PBSC) transplant using busulfan/etoposide as the preparative regimen. IV. Determine the feasibility and toxic effects of the consolidation sequence of HiDAC/etoposide/G-CSF followed by 2 courses of HiDAC in patients who would otherwise receive PBSC transplant, but are unable to do so for logistical or institutional reasons. V. Determine the feasibility of intermittent administration of high dose subcutaneous interleukin-2 (IL-2) in combination with continuous low dose subcutaneous IL-2 in patients recovering from PBSC transplant or intensive consolidation chemotherapy.
OUTLINE: This is a dose escalation study of daunorubicin in the induction therapy portion, with a separate dose escalation study of etoposide in the same portion. Patients are treated with three phases of treatment: induction, intensification, and postremission therapy. Induction therapy: Patients receive cytarabine IV as a continuous infusion on days 1-7 plus daunorubicin IV over 30 minutes and etoposide IV over 2 hours on days 1-3 (ADE regimen). Some patients also receive PSC 833 IV as a continuous infusion on days 1-3 (ADEP regimen). This course may be repeated 14 days later. Cohorts of 9 patients each receive escalating doses of daunorubicin until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose at which 3 of 9 patients experience dose limiting toxicity. Escalations are conducted separately for the ADE and ADEP regimens. Other cohorts of 9 patients each receive escalating doses of etoposide with constant doses of daunorubicin in the ADE regimen. The MTD is described in the same manner. Intensification therapy: Arm I (patients with certain genetic characteristics in their leukemia cells): Patients receive 3 additional courses of cytarabine IV over 3 hours, twice a day, for 3 days. Courses are repeated every 28 days. Arm II (patients who do not have these genetic characteristics): Patients undergo a peripheral blood stem cell (PBSC) transplant. Patients first receive high dose cytarabine IV over 2 hours on days 1-4, etoposide IV as a continuous infusion on days 1-4, and filgrastim (G-CSF) subcutaneously beginning on day 5 until blood counts recover. PBSC are then collected. Approximately 4-6 weeks later, patients receive oral busulfan 4 times a day on days 1-4 and etoposide IV over 4 hours on day 5. PBSC are reinfused on day 7. G-CSF is administered subcutaneously beginning on day 7 until blood cell counts recover. Arm III (patients who cannot undergo a PBSC transplant): Patients receive cytarabine, etoposide, and G-CSF as in arm II, then high dose cytarabine as in arm I. Postremission therapy (all patients): Patients receive low dose interleukin-2 (IL-2) by daily injection for 2 weeks. On day 15, patients begin receiving intermittent high dose IL-2 three days a week. Patients alternate these courses of IL-2: 14 days of low dose IL-2, 3 days of high dose IL-2, 1 day of rest, low dose IL-2 for 10 days, then 3 days of high dose IL-2, then 1 day of rest. This course is repeated 3 times. Patients then receive another 16 day course of low dose IL-2. Patients are followed at 1 month, then every 3 months for 2 years, then every 6 months for 2 years, then annually thereafter.
PROJECTED ACCRUAL: Approximately 410 patients will be accrued into this study within 36 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 410
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ADE Aldesleukin - ADEP ara-C - ADEP Daunorubicin - ADEP PSC-833 - ADEP Aldesleukin - ADE Etoposide - ADE Daunorubicin - ADE ara-C - ADEP Etoposide -
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (33)
University of Illinois at Chicago Health Sciences Center
🇺🇸Chicago, Illinois, United States
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
🇺🇸Baltimore, Maryland, United States
State University of New York - Upstate Medical University
🇺🇸Syracuse, New York, United States
Vermont Cancer Center
🇺🇸Burlington, Vermont, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Tennessee, Memphis Cancer Center
🇺🇸Memphis, Tennessee, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Norris Cotton Cancer Center
🇺🇸Lebanon, New Hampshire, United States
CCOP - Christiana Care Health Services
🇺🇸Wilmington, Delaware, United States
CCOP - Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
University of California San Diego Cancer Center
🇺🇸La Jolla, California, United States
CCOP - Southern Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Walter Reed Army Medical Center
🇺🇸Washington, District of Columbia, United States
UCSF Cancer Center and Cancer Research Institute
🇺🇸San Francisco, California, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Ellis Fischel Cancer Center - Columbia
🇺🇸Columbia, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
CCOP - North Shore University Hospital
🇺🇸Manhasset, New York, United States
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
🇺🇸Syracuse, New York, United States
New York Presbyterian Hospital - Cornell Campus
🇺🇸New York, New York, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Mount Sinai Medical Center, NY
🇺🇸New York, New York, United States
Lineberger Comprehensive Cancer Center, UNC
🇺🇸Chapel Hill, North Carolina, United States
CCOP - Southeast Cancer Control Consortium
🇺🇸Winston-Salem, North Carolina, United States
Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
MBCCOP - Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States