RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the
growth of cancer cells. It also helps stop the patient's immune system from rejecting the
transplanted stem cells. When the healthy stem cells are infused into the patient they may
help the patient's bone marrow make stem cells, red blood cells, white blood cells, and
platelets. If the patient's stem cells are to be transplanted, the patient is also treated
with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer
cells or deliver cancer-killing substances to them without harming normal cells. It is not
yet known whether combination chemotherapy is more effective with or without gemtuzumab
ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.
PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab
ozogamicin, and stem cell transplant to see how well they work compared to combination
chemotherapy and peripheral stem cell transplant alone in treating patients with acute
myeloid leukemia.
- To compare the overall survival (OS) between two induction regimens (standard versus
dose intense daunorubicin and cytarabine) in patients with de novo AML.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
induction therapy (standard-dose daunorubicin vs high-dose daunorubicin).
- Standard: Patients receive standard-dose daunorubicin IV over 10-15 minutes on
- High dose: Patients receive high-dose daunorubicin IV over 10-15 minutes on days
1-3 and cytarabine as in arm I.
Patients in both arms may receive a second course of induction therapy if complete remission
(CR) is not achieved after the first course. The second course is administered as in arm I
to all patients. Patients who don't achieve CR after 2 courses of induction therapy are
removed from study.
Patients who achieve CR after induction therapy proceed to post-remission therapy with
EITHER allogeneic transplantation only (on or off study) OR consolidation therapy and
autologous transplantation (on study), according to risk status and donor status.
Patients who are considered at intermediate or high risk for relapse (unfavorable
cytogenetics/high WBC) and have a suitable related donor undergo an allogeneic
transplantation. Patients with intermediate-risk cytogenetics, WBC no greater than
100,000/mm^3, and appropriate donors have the option of undergoing allogeneic
transplantation.
- Allogeneic transplantation: Within 1-3 months after recovery from induction therapy,
patients receive busulfan IV every 6 hours on days - 7 to -4 and cyclophosphamide IV
over 4 hours on days - 3 and -2. Allogeneic bone marrow or peripheral blood stem cells
(PBSCs) are infused on day 0. Patients receive graft-vs-host disease (GVHD) prophylaxis
comprising cyclosporine IV over 1-4 hours beginning on day - 1 and then orally (when
tolerated) twice daily until day 180. Alternatively, patients may receive tacrolimus IV
over 24 hours beginning on day - 1 and then orally twice daily until day 180. Patients
also receive methotrexate IV on days 1, 3, 6, and 11.
Patients who do not meet the criteria for allogeneic transplantation (i. e., are favorable
risk or do not have a matching related donor) or who opt not to undergo allogeneic
transplantation proceed to consolidation therapy followed by randomization to 1 of 2
autologous transplantation arms.
- Consolidation therapy: Beginning 2-8 weeks after recovery from induction therapy,
patients receive high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and
5. A second course is administered 3 weeks after blood recovery. Patients receive
filgrastim (G-CSF) subcutaneously (SC) daily for 4 days and then autologous PBSCs are
harvested by leukapheresis.
- Autologous stem cell transplantation: Patients are randomized to 1 of 2 autologous
comprising busulfan IV every 6 hours on days - 7 to -4 and cyclophosphamide IV over
2 hours on days - 3 and -2. Patients then undergo autologous PBSC transplantation
on day 0. Patients receive sargramostim (GM-CSF) or G-CSF IV or SC beginning on
day 0 and continuing until blood counts recover.
collection, patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and
GM-CSF SC or IV beginning on day 10 and continuing until blood counts recover.
Within 2-3 weeks after blood count recovery, patients receive conditioning and
undergo autologous PBSC transplantation as in arm I.
Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 3 months
for up to 7 years.
ACTUAL ACCRUAL: A total of 657 patients were accrued for this study.
Minimum age: 16 Years.
Maximum age: 60 Years.
Gender(s): Both.
Rambam Medical Center, Haifa 31096, Israel
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham, Birmingham, Alabama 35294, United States
Mayo Clinic Scottsdale, Scottsdale, Arizona 85259-5499, United States
Aurora Presbyterian Hospital, Aurora, Colorado 80012, United States
Penrose Cancer Center at Penrose Hospital, Colorado Springs, Colorado 80933, United States
CCOP - Colorado Cancer Research Program, Denver, Colorado 80224-2522, United States
Porter Adventist Hospital, Denver, Colorado 80210, United States
Presbyterian - St. Luke's Medical Center, Denver, Colorado 80218, United States
Rose Medical Center, Denver, Colorado 80220, United States
St. Anthony Central Hospital, Denver, Colorado 80204, United States
St. Joseph Hospital, Denver, Colorado 80218, United States
Swedish Medical Center, Englewood, Colorado 80110, United States
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center, Grand Junction, Colorado 81502, United States
North Colorado Medical Center, Greeley, Colorado 80631, United States
Sky Ridge Medical Center, Lone Tree, Colorado 80124, United States
Hope Cancer Care Center at Longmont United Hospital, Longmont, Colorado 80502, United States
McKee Medical Center, Loveland, Colorado 80539, United States
St. Mary - Corwin Regional Medical Center, Pueblo, Colorado 81004, United States
North Suburban Medical Center, Thornton, Colorado 80229, United States
Exempla Lutheran Medical Center, Wheat Ridge, Colorado 80033, United States
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus, Boca Raton, Florida 33486, United States
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - West, Boca Raton, Florida 33428, United States
University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami, Miami, Florida 33136, United States
Winship Cancer Institute of Emory University, Altanta, Georgia 30322, United States
Hematology and Oncology Associates, Chicago, Illinois 60611, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois 60611-3013, United States
Evanston Northwestern Healthcare - Evanston Hospital, Evanston, Illinois 60201-1781, United States
Joliet Oncology-Hematology Associates, Limited - West, Joliet, Illinois 60435, United States
Midwest Center for Hematology/Oncology, Joliet, Illinois 60432, United States
North Shore Oncology and Hematology Associates, Limited - Libertyville, Libertyville, Illinois 60048, United States
La Grange Oncology Associates - Geneva, Naperville, Illinois 60563, United States
Cancer Care and Hematology Specialists of Chicagoland - Niles, Niles, Illinois 60714, United States
Advocate Lutheran General Cancer Care Center, Park Ridge, Illinois 60068-1174, United States
Hematology Oncology Associates - Skokie, Skokie, Illinois 60076, United States
Carle Cancer Center at Carle Foundation Hospital, Urbana, Illinois 61801, United States
CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States
Fort Wayne Medical Oncology and Hematology, Fort Wayne, Indiana 46815, United States
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States
Tufts-NEMC Cancer Center, Boston, Massachusetts 02111, United States
Borgess Medical Center, Kalamazoo, Michigan 49001, United States
Bronson Methodist Hospital, Kalamazoo, Michigan 49007, United States
West Michigan Cancer Center, Kalamazoo, Michigan 49007-3731, United States
MeritCare Bemidji, Bemidji, Minnesota 56601, United States
Fairview Ridges Hospital, Burnsville, Minnesota 55337, United States
Mercy and Unity Cancer Center at Mercy Hospital, Coon Rapids, Minnesota 55433, United States
Fairview Southdale Hospital, Edina, Minnesota 55435, United States
Mercy and Unity Cancer Center at Unity Hospital, Fridley, Minnesota 55432, United States
Minnesota Oncology Hematology, PA - Maplewood, Maplewood, Minnesota 55109, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital, Minneapolis, Minnesota 55407, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center, Robbinsdale, Minnesota 55422-2900, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
CCOP - Metro-Minnesota, Saint Louis Park, Minnesota 55416, United States
Park Nicollet Cancer Center, Saint Louis Park, Minnesota 55416, United States
United Hospital, Saint Paul, Minnesota 55102, United States
Ridgeview Medical Center, Waconia, Minnesota 55387, United States
Minnesota Oncology Hematology, PA - Woodbury, Woodbury, Minnesota 55125, United States
Billings Clinic - Downtown, Billings, Montana 59107-7000, United States
CCOP - Montana Cancer Consortium, Billings, Montana 59101, United States
Hematology-Oncology Centers of the Northern Rockies - Billings, Billings, Montana 59101, United States
Northern Rockies Radiation Oncology Center, Billings, Montana 59101, United States
St. Vincent Healthcare Cancer Care Services, Billings, Montana 59101, United States
Bozeman Deaconess Cancer Center, Bozeman, Montana 59715, United States
St. James Healthcare Cancer Care, Butte, Montana 59701, United States
Great Falls Clinic, Great Falls, Montana 59405, United States
Great Falls Clinic - Main Facility, Great Falls, Montana 59405, United States
St. Peter's Hospital, Helena, Montana 59601, United States
Glacier Oncology, PLLC, Kalispell, Montana 59901, United States
Kalispell Medical Oncology at KRMC, Kalispell, Montana 59901, United States
Kalispell Regional Medical Center, Kalispell, Montana 59901, United States
Community Medical Center, Missoula, Montana 59801, United States
Guardian Oncology and Center for Wellness, Missoula, Montana 59804, United States
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center, Missoula, Montana 59807, United States
Montana Cancer Specialists at Montana Cancer Center, Missoula, Montana 59807-7877, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States
NYU Cancer Institute at New York University Medical Center, New York, New York 10016, United States
CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States
MeritCare Broadway, Fargo, North Dakota 58122, United States
Aultman Cancer Center at Aultman Hospital, Canton, Ohio 44710-1799, United States
Mercy Cancer Center at Mercy Medical Center, Canton, Ohio 44708, United States
Jewish Hospital Cancer Center, Cincinnati, Ohio 45236, United States
St. Rita's Medical Center, Lima, Ohio 45801, United States
Geisinger Cancer Institute at Geisinger Health, Danville, Pennsylvania 17822-0001, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States
Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, United States
Fox Chase Cancer Center - Philadelphia, Philadelphia, Pennsylvania 19111-2497, United States
UPMC Cancer Centers, Pittsburgh, Pennsylvania 15232, United States
Geisinger Medical Group - Scenery Park, State College, Pennsylvania 16801, United States
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania 18711, United States
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6838, United States
Virginia Commonwealth University Massey Cancer Center, Richmond, Virginia 23298-0037, United States
Marshfield Clinic Cancer Care at Regional Cancer Center, Eau Claire, Wisconsin 54701, United States
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center, La Crosse, Wisconsin 54601, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States
Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States
Saint Joseph's Hospital, Marshfield, Wisconsin 54449, United States
Ministry Medical Group at Saint Mary's Hospital, Rhinelander, Wisconsin 54501, United States
Marshfield Clinic - Weston Center, Weston, Wisconsin 54476, United States
Welch Cancer Center at Sheridan Memorial Hospital, Sheridan, Wyoming 82801, United States