RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from
dividing so they stop growing or die. Monoclonal antibodies such as gemtuzumab ozogamicin
can locate cancer cells and either kill them or deliver cancer-killing substances to them
without harming normal cells. Combining monoclonal antibody therapy with combination
chemotherapy may kill more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of combining gemtuzumab ozogamicin with
combination chemotherapy in treating children who have relapsed or refractory acute myeloid
leukemia or myelodysplastic syndrome.
- Determine the safety and maximum tolerated dose of gemtuzumab ozogamicin in combination
with conventional chemotherapy in patients with relapsed or refractory acute myeloid
leukemia or myelodysplastic syndromes.
- Correlate the likelihood of leukemic blast cells to undergo apoptosis in vitro with the
- Correlate drug resistance as manifested by dye efflux or multiple drug resistance-1
expression by leukemic blast cells with the efficacy of this regimen in these patients.
OUTLINE: This is a dose-escalation, multicenter study of gemtuzumab ozogamicin. Patients are
assigned by cohort to 1 of 2 treatment regimens.
- Regimen A: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-4,
mitoxantrone IV over 1 hour on days 3-6, and gemtuzumab ozogamicin IV over 2 hours on
day 7.
- Regimen B: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8,
and 9, asparaginase intramuscularly on days 2 and 9, and gemtuzumab ozogamicin IV over
2 hours on day 3.
Cohorts of 3-6 patients receive de-escalating doses of gemtuzumab ozogamicin until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose below that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed monthly for 6 months, every 2 months for 6 months, every 6 months for
2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 1. 5 years.
Minimum age: N/A.
Maximum age: 21 Years.
Gender(s): Both.
Comprehensive Cancer Center at University of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital, Long Beach, California 90801, United States
Children's Hospital Los Angeles, Los Angeles, California 90027, United States
Children's Hospital of Orange County, Orange, California 92868, United States
Children's Hospital and Health Center - San Diego, San Diego, California 92123-4282, United States
Stanford Cancer Center at Stanford University Medical Center, Stanford, California 94305, United States
Children's Hospital Cancer Center, Denver, Colorado 80218-1088, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando, Orlando, Florida 32803-1273, United States
All Children's Hospital, St. Petersburg, Florida 33701, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital, Tampa, Florida 33607, United States
Kaplan Cancer Center at St. Mary's Medical Center, West Palm Beach, Florida 33407, United States
Emory University Hospital - Atlanta, Atlanta, Georgia 30322, United States
Cancer Research Center of Hawaii, Honolulu, Hawaii 95813, United States
Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States
St. Vincent Indianapolis Hospital, Indianapolis, Indiana 46260, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084, United States
CancerCare of Maine at Eastern Maine Medial Center, Bangor, Maine 04401, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore, Maryland 21215, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
C.S. Mott Children's Hospital at University of Michigan, Ann Arbor, Michigan 48109-0238, United States
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan 48236, United States
Children's Hospital of Minnesota - Minneapolis, Minneapolis, Minnesota 55404, United States
Fairview University Medical Center - University Campus, Minneapolis, Minnesota 55455, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States
Children's Mercy Hospital, Kansas City, Missouri 64108, United States
Siteman Cancer Center at Barnes-Jewish Hospital, St. Louis, Missouri 63110, United States
Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey 07601, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States
Newark Beth Israel Medical Center, Newark, New Jersey 07112, United States
Herbert Irving Comprehensive Cancer Center at Columbia University, New York, New York 10032, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States
SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States
Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States
Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States
Children's Hospital Medical Center of Akron, Akron, Ohio 44308-1062, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States
Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195-5217, United States
Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States
Columbus Children's Hospital, Columbus, Ohio 43205-2696, United States
Children's Medical Center - Dayton, Dayton, Ohio 45404-1815, United States
Tod Children's Hospital - Forum Health, Youngstown, Ohio 44501, United States
Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States
McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada
Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-9786, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada
McGill Cancer Centre at McGill University, Montreal, Quebec H3H 1P3, Canada
Centre Hospitalier Universitaire de Quebec, Ste-Foy, Quebec G1V 4G2, Canada
Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425, United States
Greenville Hospital System Cancer Center, Greenville, South Carolina 29605, United States
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6310, United States
Texas Tech University Health Sciences Center School of Medicine, Amarillo, Texas 79106, United States
Children's Hospital of Austin, Austin, Texas 78701, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States
Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104-9958, United States
M.D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States
Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States
University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7811, United States
Massey Cancer Center at Virginia Commonwealth University, Richmond, Virginia 23298-0037, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Providence Cancer Center at Sacred Heart Medical Center, Spokane, Washington 99220-2555, United States
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital, Huntington, West Virginia 25701, United States
Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States
Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States
Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States