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

July 12, 2016 updated by: Alliance for Clinical Trials in Oncology

A Dose Escalation And Phase II Study Of Gemtuzumab Ozogamicin (CMA-676; Mylotarg) With High-Dose Cytarabine For Patients With Refractory Or Relapsed Acute Myeloid Leukemia (AML)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936-5067
        • University of Puerto Rico School of Medicine Medical Sciences Campus
  • United States
    • Alabama
      • Anniston, Alabama, United States, 36207
        • Northeast Alabama Regional Medical Center
      • Birmingham, Alabama, United States, 35233-1996
        • Veterans Affairs Medical Center - Birmingham
    • California
      • La Jolla, California, United States, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • San Diego, California, United States, 92161
        • Veterans Affairs Medical Center - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Comprehensive Cancer Center
      • San Francisco, California, United States, 94121
        • Veterans Affairs Medical Center - San Francisco
    • Delaware
      • Newark, Delaware, United States, 19713
        • CCOP - Christiana Care Health Services
    • District of Columbia
      • Washington, District of Columbia, United States, 20307-5000
        • Walter Reed Army Medical Center
      • Washington, District of Columbia, United States, 20422
        • Veterans Affairs Medical Center - Washington, DC
      • Washington, District of Columbia, United States, 20007
        • Lombardi Cancer Center at Georgetown University Medical Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • Broward General Medical Center
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital Comprehensive Cancer Center
      • Miami Beach, Florida, United States, 33140
        • CCOP - Mount Sinai Medical Center
      • Orlando, Florida, United States, 32804
        • Florida Hospital Cancer Institute
      • West Palm Beach, Florida, United States, 33401
        • Palm Beach Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Veterans Affairs Medical Center - Chicago (Westside Hospital)
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Cancer Research Center
      • Chicago, Illinois, United States, 60640
        • Louis A. Weiss Memorial Hospital
      • Peoria, Illinois, United States, 61602
        • CCOP - Illinois Oncology Research Association
      • River Forest, Illinois, United States, 60305
        • West Suburban Center for Cancer Care
      • Rockford, Illinois, United States, 61108
        • Saint Anthony Medical Center
    • Indiana
      • Fort Wayne, Indiana, United States, 46885-5099
        • Fort Wayne Medical Oncology and Hematology, Incorporated
    • Iowa
      • Bettendorf, Iowa, United States, 52722
        • Hematology Oncology Associates of the Quad Cities
      • Iowa City, Iowa, United States, 52242-1009
        • Holden Comprehensive Cancer Center at University of Iowa
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Baptist Hospital East - Louisville
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Marlene and Stewart Greenebaum Cancer Center, University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Memorial Medical Center - University Campus
    • Michigan
      • Saint Joseph, Michigan, United States, 49085
        • Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Veterans Affairs Medical Center - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
    • Missouri
      • Columbia, Missouri, United States, 65201
        • Veterans Affairs Medical Center - Columbia (Truman Memorial)
      • Columbia, Missouri, United States, 65203
        • Ellis Fischel Cancer Center at University of Missouri - Columbia
      • Kansas City, Missouri, United States, 64131
        • CCOP - Kansas City
      • St. Louis, Missouri, United States, 63110
        • Barnes-Jewish Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • CCOP - Southern Nevada Cancer Research Foundation
      • Las Vegas, Nevada, United States, 89106
        • Veterans Affairs Medical Center - Las Vegas
    • New Hampshire
      • Hooksett, New Hampshire, United States, 03106
        • New Hampshire Oncology-Hematology, PA - Hooksett
      • Lebanon, New Hampshire, United States, 03756-0002
        • Norris Cotton Cancer Center at Dartmouth Medical School
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper University Hospital
    • New York
      • Buffalo, New York, United States, 14215
        • Veterans Affairs Medical Center - Buffalo
      • Elmhurst, New York, United States, 11373
        • Elmhurst Hospital Center
      • Jamaica, New York, United States, 11432
        • Queens Cancer Center of Queens Hospital
      • Manhasset, New York, United States, 11030
        • CCOP - North Shore University Hospital
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center, NY
      • New York, New York, United States, 10021
        • New York Weill Cornell Cancer Center at Cornell University
      • Syracuse, New York, United States, 13210
        • Veterans Affairs Medical Center - Syracuse
      • Syracuse, New York, United States, 13217
        • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
      • Syracuse, New York, United States, 13210
        • University Hospital at State University of New York - Upstate Medical University
    • North Carolina
      • Asheville, North Carolina, United States, 28805
        • Veterans Affairs Medical Center - Asheville
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
      • Concord, North Carolina, United States, 28025
        • NorthEast Oncology Associates
      • Durham, North Carolina, United States, 27705
        • Veterans Affairs Medical Center - Durham
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
      • Fayetteville, North Carolina, United States, 28302-2000
        • Cape Fear Valley Health System
      • Kinston, North Carolina, United States, 28503-1678
        • Lenoir Memorial Hospital Cancer Center
      • Pinehurst, North Carolina, United States, 28374
        • FirstHealth Moore Regional Hospital
      • Wilmington, North Carolina, United States, 28402-9025
        • New Hanover Regional Medical Center
      • Winston-Salem, North Carolina, United States, 27104-4241
        • CCOP - Southeast Cancer Control Consortium
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Comprehensive Cancer Center at Wake Forest University
    • Ohio
      • Columbus, Ohio, United States, 43210-1240
        • Arthur G. James Cancer Hospital - Ohio State University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Medical Center at University of Oklahoma Health Sciences Center
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Lifespan: The Miriam Hospital
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Veterans Affairs Medical Center - Memphis
      • Memphis, Tennessee, United States, 38103
        • University of Tennessee Cancer Institute
    • Texas
      • Dallas, Texas, United States, 75216
        • Veterans Affairs Medical Center - Dallas
    • Vermont
      • Bennington, Vermont, United States, 05201
        • Green Mountain Oncology Group
      • Burlington, Vermont, United States, 05401-3498
        • Vermont Cancer Center at University of Vermont
      • White River Junction, Vermont, United States, 05009
        • Veterans Affairs Medical Center - White River Junction
    • Virginia
      • Charlottesville, Virginia, United States, 22902
        • Martha Jefferson Hospital
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates - Norfolk
      • Richmond, Virginia, United States, 23298-0037
        • MBCCOP - Massey Cancer Center
      • Roanoke, Virginia, United States, 24014
        • Oncology and Hematology Associates of Southwest Virginia, Inc.
    • West Virginia
      • Huntington, West Virginia, United States, 25701
        • St. Mary's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort I
Immunotherapy with gemtuzumab
Biological: 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)
Other Names:
  • Mylotarg
Experimental: Cohort II
Gemtuzumab + ara-C
Biological: 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)
Other Names:
  • Mylotarg
Drug: ara-C
3 g/sq m IV infusion over 3 hours Days 1-5
Other Names:
  • Cytarabine
Experimental: Cohort IA
Gemtuzumab + ara C
Biological: 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)
Other Names:
  • Mylotarg
Drug: ara-C
3 g/sq m IV infusion over 3 hours Days 1-5
Other Names:
  • Cytarabine
Experimental: Cohort IV
Gemtuzumab + ara-C
Biological: 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)
Other Names:
  • Mylotarg
Drug: ara-C
3 g/sq m IV infusion over 3 hours Days 1-5
Other Names:
  • Cytarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete remission rate
Time Frame: 8 or 14 days after tx initiation & 30 d post tx
8 or 14 days after tx initiation & 30 d post tx

Secondary Outcome Measures

Outcome Measure
Time Frame
Toxicity
Time Frame: D 14, then 30, 60 , & 90 d post Tx, q 3 mon for 1 yr, then at relapse or death
D 14, then 30, 60 , & 90 d post Tx, q 3 mon for 1 yr, then at relapse or death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Richard Stone, MD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2001

Primary Completion (Actual)

December 1, 2004

Study Completion (Actual)

May 1, 2005

Study Registration Dates

First Submitted

September 11, 2000

First Submitted That Met QC Criteria

September 2, 2003

First Posted (Estimate)

September 3, 2003

Study Record Updates

Last Update Posted (Estimate)

July 14, 2016

Last Update Submitted That Met QC Criteria

July 12, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CALGB-19902
  • U10CA031946 (U.S. NIH Grant/Contract)
  • CDR0000068208 (Registry Identifier: NCI Physician Data Query)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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