A Dose Finding Study of the Safety of Gemtuzumab Ozogamicin Combined With Conventional Chemotherapy for Patients With Relapsed or Refractory Acute Myeloid Leukemia
N/A
21 Years
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
A Dose Finding Study of the Safety of Gemtuzumab Ozogamicin Combined With Conventional Chemotherapy for Patients With Relapsed or Refractory Acute Myeloid Leukemia
OBJECTIVES:
- 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.
- Determine the efficacy of this regimen in these patients.
- Correlate the likelihood of leukemic blast cells to undergo apoptosis in vitro with the
efficacy of this regimen in these patients.
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of primary acute myeloid leukemia (AML) or myelodysplastic syndromes
- Relapsed (remission duration less than 1 year) OR
- Failed induction (failed to achieve an initial complete response)
- Patients with AML as a second malignant neoplasm allowed provided no other prior
therapy for AML
- M2 or M3 bone marrow aspirate at time of study entry
- No Fanconi's anemia
- No known CNS leukemia
PATIENT CHARACTERISTICS:
Age:
- 21 and under
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin no greater than 1.5 times normal
- AST or ALT less than 2.5 times upper limit of normal
- No history of veno-occlusive disease of the liver defined as weight increase of more
than 5% over baseline and serum bilirubin greater than 5 mg/dL within 20 days after
receipt of chemotherapy
Renal:
- Creatinine no greater than 1.5 times normal OR
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70
mL/min OR
- Equivalent GFR by institutional normal range
Cardiovascular:
- Shortening fraction more than 27% by echocardiogram or normal for institution OR
- Ejection fraction more than 50% by MUGA
Other:
- Not pregnant or nursing
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 180 days since prior hematopoietic stem cell transplantation
Chemotherapy:
- Not specified
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Richard Aplenc, MD, MSCE
Investigator Role:
Study Chair
Investigator Affiliation:
Children's Hospital of Philadelphia
Authority:
United States: Federal Government
Study ID:
CDR0000069145
NCT ID:
NCT00028899
Start Date:
July 2002
Completion Date:
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- recurrent childhood acute myeloid leukemia
- secondary acute myeloid leukemia
- previously treated myelodysplastic syndromes
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Emory University Hospital - Atlanta | Atlanta, Georgia 30322 |
| Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
| Van Elslander Cancer Center at St. John Hospital and Medical Center | Grosse Pointe Woods, Michigan 48236 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
| Newark Beth Israel Medical Center | Newark, New Jersey 07112 |
| University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
| Siteman Cancer Center at Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| All Children's Hospital | St. Petersburg, Florida 33701 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
| Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
| Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
| Children's Hospital Medical Center of Akron | Akron, Ohio 44308 |
| Children's Medical Center - Dayton | Dayton, Ohio 45404 |
| Texas Tech University Health Sciences Center School of Medicine | Amarillo, Texas 79106 |
| Children's Hospital of Austin | Austin, Texas 78701 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Markey Cancer Center at University of Kentucky Chandler Medical Center | Lexington, Kentucky 40536-0084 |
| Herbert Irving Comprehensive Cancer Center at Columbia University | New York, New York 10032 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
| Fairview University Medical Center - University Campus | Minneapolis, Minnesota 55455 |
| Oklahoma University Medical Center | Oklahoma City, Oklahoma 73104 |
| M.D. Anderson Cancer Center at University of Texas | Houston, Texas 77030 |
| Stanford Cancer Center at Stanford University Medical Center | Stanford, California 94305 |
| Comprehensive Cancer Center at University of Alabama at Birmingham | Birmingham, Alabama 35294 |
| Jonathan Jaques Children's Cancer Center at Miller Children's Hospital | Long Beach, California 90801 |
| Children's Hospital and Health Center - San Diego | San Diego, California 92123-4282 |
| University of Florida Shands Cancer Center | Gainesville, Florida 32610-0232 |
| Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
| St. Joseph's Cancer Institute at St. Joseph's Hospital | Tampa, Florida 33607 |
| Kaplan Cancer Center at St. Mary's Medical Center | West Palm Beach, Florida 33407 |
| St. Vincent Indianapolis Hospital | Indianapolis, Indiana 46260 |
| CancerCare of Maine at Eastern Maine Medial Center | Bangor, Maine 04401 |
| Alvin and Lois Lapidus Cancer Institute at Sinai Hospital | Baltimore, Maryland 21215 |
| C.S. Mott Children's Hospital at University of Michigan | Ann Arbor, Michigan 48109-0238 |
| SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
| Tod Children's Hospital - Forum Health | Youngstown, Ohio 44501 |
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
| Greenville Hospital System Cancer Center | Greenville, South Carolina 29605 |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
| Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
| Massey Cancer Center at Virginia Commonwealth University | Richmond, Virginia 23298-0037 |
| Providence Cancer Center at Sacred Heart Medical Center | Spokane, Washington 99220-2555 |
| Edwards Comprehensive Cancer Center at Cabell Huntington Hospital | Huntington, West Virginia 25701 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey 08903 |
| Cancer Center at Hackensack University Medical Center | Hackensack, New Jersey 07601 |
| Children's Hospital Cancer Center | Denver, Colorado 80218 |
| Columbus Children's Hospital | Columbus, Ohio 43205-2696 |
| Children's Hospital of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
