Monoclonal Antibody Plus Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00028899

Purpose

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.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Drug: asparaginase Drug: cytarabine Drug: gemtuzumab ozogamicin Drug: mitoxantrone hydrochloride	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Dose Finding Study of the Safety of Gemtuzumab Ozogamicin Combined With Conventional Chemotherapy for Patients With Relapsed or Refractory Acute Myeloid Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Cytarabine hydrochloride Mitoxantrone Mitoxantrone hydrochloride Gemtuzumab ozogamicin Cytarabine L-Asparaginase

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

July 2002

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00028899

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Locations

United States, Alabama
Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016-7710
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital and Health Center - San Diego
San Diego, California, United States, 92123-4282
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital of Orange County
Orange, California, United States, 92868
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States, 90801
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305
United States, Colorado
Children's Hospital Cancer Center
Denver, Colorado, United States, 80218-1088
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Florida
All Children's Hospital
St. Petersburg, Florida, United States, 33701
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 95813
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
United States, Kentucky
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0084
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
C.S. Mott Children's Hospital at University of Michigan
Ann Arbor, Michigan, United States, 48109-0238
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
United States, Minnesota
Children's Hospital of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Fairview University Medical Center - University Campus
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Siteman Cancer Center at Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195-5217
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
Tod Children's Hospital - Forum Health
Youngstown, Ohio, United States, 44501
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-9786
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Greenville Hospital System Cancer Center
Greenville, South Carolina, United States, 29605
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6310
United States, Texas
Children's Hospital of Austin
Austin, Texas, United States, 78701
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104-9958
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229-3993
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Texas Tech University Health Sciences Center School of Medicine
Amarillo, Texas, United States, 79106
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-7811
United States, Virginia
Massey Cancer Center at Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0037
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, United States, 99220-2555
United States, West Virginia
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
Huntington, West Virginia, United States, 25701
United States, Wisconsin
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, Ontario
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H3H 1P3

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Richard Aplenc, MD, MSCE

Children's Hospital of Philadelphia

Study ID Numbers:	CDR0000069145, COG-AAML00P2
Study First Received:	January 4, 2002
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00028899 History of Changes
Health Authority:	United States: Federal Government