Gemtuzumab Ozogamicin and High-Dose Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT ID: NCT00006265

Last Updated: 2016-07-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-03-31

Study Completion Date

2005-05-31

Brief Summary

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RATIONALE: 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. Drugs used in chemotherapy, such as cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining gemtuzumab ozogamicin with cytarabine may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining gemtuzumab ozogamicin with high-dose cytarabine in treating patients who have relapsed or refractory acute myeloid leukemia.

Detailed Description

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OBJECTIVES:

* Determine the response rate in patients with relapsed or refractory acute myeloid leukemia treated with gemtuzumab ozogamicin (CMA-676) and high-dose cytarabine.
* Determine the safety and toxicity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gemtuzumab ozogamicin (CMA-676) (phase I closed to accrual effective 08/25/2003). Patients are stratified according to disease status (refractory vs relapsed).

* Phase I (closed to accrual effective 08/25/2003): Patients are enrolled in one of four cohorts.

* Cohort I (closed to accrual as of 10/1/02): Patients receive CMA-676 at the first dose level IV over 2 hours on days 1 and 8.
* Cohort IA (open to accrual as of 10/15/02): Patients receive high-dose cytarabine (HD-ARA-C) IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7.
* Cohort II: Patients receive HD-ARA-C as in cohort IA and CMA-676 at the first dose level IV over 2 hours on days 7 and 14.
* Cohort IV: Patients receive CMA-676 at the second dose level and HD-ARA-C as in cohort II.

Dose escalation stops if at least 3 of 9 patients experience dose-limiting toxicity.

* Phase II: Patients receive HD-ARA-C IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7 (one course).

Patients are followed at 1 month, monthly for 6 months, every 3 months for 2 years, and then annually for 10 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of the study and a total of 37 patients will be accrued for phase II of the study within 2 years. (Phase I closed to accrual effective 08/25/2003).

Conditions

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Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort I

Immunotherapy with gemtuzumab

Group Type EXPERIMENTAL

gemtuzumab ozogamicin

Intervention Type BIOLOGICAL

9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, \& IV); \& D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) \& D 14 (Cohort II)

Cohort II

Gemtuzumab + ara-C

Group Type EXPERIMENTAL

ara-C

Intervention Type DRUG

3 g/sq m IV infusion over 3 hours Days 1-5

gemtuzumab ozogamicin

Intervention Type BIOLOGICAL

9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, \& IV); \& D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) \& D 14 (Cohort II)

Cohort IA

Gemtuzumab + ara C

Group Type EXPERIMENTAL

ara-C

Intervention Type DRUG

3 g/sq m IV infusion over 3 hours Days 1-5

gemtuzumab ozogamicin

Intervention Type BIOLOGICAL

9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, \& IV); \& D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) \& D 14 (Cohort II)

Cohort IV

Gemtuzumab + ara-C

Group Type EXPERIMENTAL

ara-C

Intervention Type DRUG

3 g/sq m IV infusion over 3 hours Days 1-5

gemtuzumab ozogamicin

Intervention Type BIOLOGICAL

9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, \& IV); \& D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) \& D 14 (Cohort II)

Interventions

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ara-C

3 g/sq m IV infusion over 3 hours Days 1-5

Intervention Type DRUG

gemtuzumab ozogamicin

9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, \& IV); \& D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) \& D 14 (Cohort II)

Intervention Type BIOLOGICAL

Other Intervention Names

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Cytarabine Mylotarg

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* One of the following diagnoses:

* Primary refractory acute myeloid leukemia (AML)

* More than 10% blasts in the bone marrow or blood after recovery from 2 courses of standard cytarabine- and anthracycline-based induction chemotherapy
* No prior remission
* Relapsed AML

* More than 10% blasts in the bone marrow or blood after documented remission
* Prior remission lasted more than 30 days
* No prior treatment for current relapse
* CD33 expression on at least 20% of leukemia blast cells at initial diagnosis for primary refractory patients or at the time of relapse for all other patients
* No active CNS involvement

PATIENT CHARACTERISTICS:

Age:

* 17 and over

Performance status:

* 0-2

Life expectancy:

* Not specified

Hematopoietic:

* See Disease Characteristics
* WBC less than 30,000/mm\^3

Hepatic:

* Bilirubin less than 2.0 mg/dL
* No veno-occlusive disease of the liver
* No chronic liver disease unless due to AML

Renal:

* Not specified

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No active serious infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 6 months since prior stem cell transplantation

Chemotherapy:

* See Disease Characteristics
* Prior etoposide and/or thioguanine during remission induction allowed
* Prior hydroxyurea for control of AML allowed
* At least 24 hours since prior hydroxyurea
* At least 3 months since prior high-dose cytarabine (greater than 2 g/m\^2/dose)-containing regimen
* No other concurrent chemotherapy

Endocrine therapy:

* Concurrent steroids for adrenal failure, hypersensitivity reactions, or septic shock allowed
* Concurrent ophthalmic corticosteroids allowed
* Concurrent hormones for nondisease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic conditions) allowed

Radiotherapy:

* No concurrent radiotherapy

Surgery:

* Not specified

Other:

* More than 2 months since prior cytotoxic therapy
Minimum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard Stone, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

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Northeast Alabama Regional Medical Center

Anniston, Alabama, United States

Site Status

Veterans Affairs Medical Center - Birmingham

Birmingham, Alabama, United States

Site Status

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Site Status

Veterans Affairs Medical Center - San Diego

San Diego, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

Lombardi Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

Veterans Affairs Medical Center - Washington, DC

Washington D.C., District of Columbia, United States

Site Status

Broward General Medical Center

Fort Lauderdale, Florida, United States

Site Status

Memorial Regional Hospital Comprehensive Cancer Center

Hollywood, Florida, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Florida Hospital Cancer Institute

Orlando, Florida, United States

Site Status

Palm Beach Cancer Institute

West Palm Beach, Florida, United States

Site Status

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Louis A. Weiss Memorial Hospital

Chicago, Illinois, United States

Site Status

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Site Status

West Suburban Center for Cancer Care

River Forest, Illinois, United States

Site Status

Saint Anthony Medical Center

Rockford, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology, Incorporated

Fort Wayne, Indiana, United States

Site Status

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Baptist Hospital East - Louisville

Louisville, Kentucky, United States

Site Status

Marlene and Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center - University Campus

Worcester, Massachusetts, United States

Site Status

Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph

Saint Joseph, Michigan, United States

Site Status

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, United States

Site Status

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Veterans Affairs Medical Center - Las Vegas

Las Vegas, Nevada, United States

Site Status

New Hampshire Oncology-Hematology, PA - Hooksett

Hooksett, New Hampshire, United States

Site Status

Norris Cotton Cancer Center at Dartmouth Medical School

Lebanon, New Hampshire, United States

Site Status

Cooper University Hospital

Camden, New Jersey, United States

Site Status

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, United States

Site Status

Elmhurst Hospital Center

Elmhurst, New York, United States

Site Status

Queens Cancer Center of Queens Hospital

Jamaica, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Mount Sinai Medical Center, NY

New York, New York, United States

Site Status

University Hospital at State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

Site Status

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Asheville

Asheville, North Carolina, United States

Site Status

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

NorthEast Oncology Associates

Concord, North Carolina, United States

Site Status

Veterans Affairs Medical Center - Durham

Durham, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Cape Fear Valley Health System

Fayetteville, North Carolina, United States

Site Status

Lenoir Memorial Hospital Cancer Center

Kinston, North Carolina, United States

Site Status

FirstHealth Moore Regional Hospital

Pinehurst, North Carolina, United States

Site Status

New Hanover Regional Medical Center

Wilmington, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Site Status

Oklahoma University Medical Center at University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Lifespan: The Miriam Hospital

Providence, Rhode Island, United States

Site Status

University of Tennessee Cancer Institute

Memphis, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Memphis

Memphis, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Dallas

Dallas, Texas, United States

Site Status

Green Mountain Oncology Group

Bennington, Vermont, United States

Site Status

Vermont Cancer Center at University of Vermont

Burlington, Vermont, United States

Site Status

Veterans Affairs Medical Center - White River Junction

White River Junction, Vermont, United States

Site Status

Martha Jefferson Hospital

Charlottesville, Virginia, United States

Site Status

Virginia Oncology Associates - Norfolk

Norfolk, Virginia, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Oncology and Hematology Associates of Southwest Virginia, Inc.

Roanoke, Virginia, United States

Site Status

St. Mary's Medical Center

Huntington, West Virginia, United States

Site Status

University of Puerto Rico School of Medicine Medical Sciences Campus

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Stone RM, Moser B, Sanford B, Schulman P, Kolitz JE, Allen S, Stock W, Galinsky I, Vij R, Marcucci G, Hurd D, Larson RA; Cancer and Leukemia Group B. High dose cytarabine plus gemtuzumab ozogamicin for patients with relapsed or refractory acute myeloid leukemia: Cancer and Leukemia Group B study 19902. Leuk Res. 2011 Mar;35(3):329-33. doi: 10.1016/j.leukres.2010.07.017. Epub 2010 Aug 4.

Reference Type RESULT
PMID: 20688393 (View on PubMed)

Stone RM, Moser B, Schulman P, et al.: A dose escalation and phase II study of gemtuzumab ozogamicin (GO) with high-dose cytarabine (HiDAC) for patients (pts) with refractory or relapsed acute myeloid leukemia (AML): CALGB 19902. [Abstract] Blood 104 (11): A-873, 2004.

Reference Type RESULT

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-19902

Identifier Type: -

Identifier Source: secondary_id

CDR0000068208

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-19902

Identifier Type: -

Identifier Source: org_study_id

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