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

Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Completed
CT.gov ID
NCT00006265
Collaborator
National Cancer Institute (NCI) (NIH)
60
Enrollment
78
Locations
4
Arms
50
Duration (Months)
0.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Study Start Date :
Mar 1, 2001
Actual Primary Completion Date :
Dec 1, 2004
Actual Study Completion Date :
May 1, 2005

Arms and Interventions

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

    Drug: ara-C
    3 g/sq m IV infusion over 3 hours Days 1-5
    Other Names:
  • Cytarabine

    • 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 IA

    Gemtuzumab + ara C

    Drug: ara-C
    3 g/sq m IV infusion over 3 hours Days 1-5
    Other Names:
  • Cytarabine

    • 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 IV

    Gemtuzumab + ara-C

    Drug: ara-C
    3 g/sq m IV infusion over 3 hours Days 1-5
    Other Names:
  • Cytarabine

    • 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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Complete remission rate [8 or 14 days after tx initiation & 30 d post tx]

    Secondary Outcome Measures

    1. Toxicity [D 14, then 30, 60 , & 90 d post Tx, q 3 mon for 1 yr, then at relapse or death]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    17 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Northeast Alabama Regional Medical Center Anniston Alabama United States 36207
    2 Veterans Affairs Medical Center - Birmingham Birmingham Alabama United States 35233-1996
    3 Rebecca and John Moores UCSD Cancer Center La Jolla California United States 92093-0658
    4 Veterans Affairs Medical Center - San Diego San Diego California United States 92161
    5 UCSF Comprehensive Cancer Center San Francisco California United States 94115
    6 Veterans Affairs Medical Center - San Francisco San Francisco California United States 94121
    7 CCOP - Christiana Care Health Services Newark Delaware United States 19713
    8 Lombardi Cancer Center at Georgetown University Medical Center Washington District of Columbia United States 20007
    9 Walter Reed Army Medical Center Washington District of Columbia United States 20307-5000
    10 Veterans Affairs Medical Center - Washington, DC Washington District of Columbia United States 20422
    11 Broward General Medical Center Fort Lauderdale Florida United States 33316
    12 Memorial Regional Hospital Comprehensive Cancer Center Hollywood Florida United States 33021
    13 CCOP - Mount Sinai Medical Center Miami Beach Florida United States 33140
    14 Florida Hospital Cancer Institute Orlando Florida United States 32804
    15 Palm Beach Cancer Institute West Palm Beach Florida United States 33401
    16 Veterans Affairs Medical Center - Chicago (Westside Hospital) Chicago Illinois United States 60612
    17 University of Chicago Cancer Research Center Chicago Illinois United States 60637-1470
    18 Louis A. Weiss Memorial Hospital Chicago Illinois United States 60640
    19 CCOP - Illinois Oncology Research Association Peoria Illinois United States 61602
    20 West Suburban Center for Cancer Care River Forest Illinois United States 60305
    21 Saint Anthony Medical Center Rockford Illinois United States 61108
    22 Fort Wayne Medical Oncology and Hematology, Incorporated Fort Wayne Indiana United States 46885-5099
    23 Hematology Oncology Associates of the Quad Cities Bettendorf Iowa United States 52722
    24 Holden Comprehensive Cancer Center at University of Iowa Iowa City Iowa United States 52242-1009
    25 Baptist Hospital East - Louisville Louisville Kentucky United States 40207
    26 Marlene and Stewart Greenebaum Cancer Center, University of Maryland Baltimore Maryland United States 21201
    27 Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston Massachusetts United States 02115
    28 University of Massachusetts Memorial Medical Center - University Campus Worcester Massachusetts United States 01655
    29 Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph Saint Joseph Michigan United States 49085
    30 Veterans Affairs Medical Center - Minneapolis Minneapolis Minnesota United States 55417
    31 University of Minnesota Cancer Center Minneapolis Minnesota United States 55455
    32 Veterans Affairs Medical Center - Columbia (Truman Memorial) Columbia Missouri United States 65201
    33 Ellis Fischel Cancer Center at University of Missouri - Columbia Columbia Missouri United States 65203
    34 CCOP - Kansas City Kansas City Missouri United States 64131
    35 Barnes-Jewish Hospital St. Louis Missouri United States 63110
    36 UNMC Eppley Cancer Center at the University of Nebraska Medical Center Omaha Nebraska United States 68198-7680
    37 CCOP - Southern Nevada Cancer Research Foundation Las Vegas Nevada United States 89106
    38 Veterans Affairs Medical Center - Las Vegas Las Vegas Nevada United States 89106
    39 New Hampshire Oncology-Hematology, PA - Hooksett Hooksett New Hampshire United States 03106
    40 Norris Cotton Cancer Center at Dartmouth Medical School Lebanon New Hampshire United States 03756-0002
    41 Cooper University Hospital Camden New Jersey United States 08103
    42 Veterans Affairs Medical Center - Buffalo Buffalo New York United States 14215
    43 Elmhurst Hospital Center Elmhurst New York United States 11373
    44 Queens Cancer Center of Queens Hospital Jamaica New York United States 11432
    45 CCOP - North Shore University Hospital Manhasset New York United States 11030
    46 North Shore University Hospital Manhasset New York United States 11030
    47 Memorial Sloan-Kettering Cancer Center New York New York United States 10021
    48 New York Weill Cornell Cancer Center at Cornell University New York New York United States 10021
    49 Mount Sinai Medical Center, NY New York New York United States 10029
    50 University Hospital at State University of New York - Upstate Medical University Syracuse New York United States 13210
    51 Veterans Affairs Medical Center - Syracuse Syracuse New York United States 13210
    52 CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. Syracuse New York United States 13217
    53 Veterans Affairs Medical Center - Asheville Asheville North Carolina United States 28805
    54 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill North Carolina United States 27599-7295
    55 NorthEast Oncology Associates Concord North Carolina United States 28025
    56 Veterans Affairs Medical Center - Durham Durham North Carolina United States 27705
    57 Duke Comprehensive Cancer Center Durham North Carolina United States 27710
    58 Cape Fear Valley Health System Fayetteville North Carolina United States 28302-2000
    59 Lenoir Memorial Hospital Cancer Center Kinston North Carolina United States 28503-1678
    60 FirstHealth Moore Regional Hospital Pinehurst North Carolina United States 28374
    61 New Hanover Regional Medical Center Wilmington North Carolina United States 28402-9025
    62 CCOP - Southeast Cancer Control Consortium Winston-Salem North Carolina United States 27104-4241
    63 Comprehensive Cancer Center at Wake Forest University Winston-Salem North Carolina United States 27157-1082
    64 Arthur G. James Cancer Hospital - Ohio State University Columbus Ohio United States 43210-1240
    65 Oklahoma University Medical Center at University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    66 Lifespan: The Miriam Hospital Providence Rhode Island United States 02906
    67 University of Tennessee Cancer Institute Memphis Tennessee United States 38103
    68 Veterans Affairs Medical Center - Memphis Memphis Tennessee United States 38104
    69 Veterans Affairs Medical Center - Dallas Dallas Texas United States 75216
    70 Green Mountain Oncology Group Bennington Vermont United States 05201
    71 Vermont Cancer Center at University of Vermont Burlington Vermont United States 05401-3498
    72 Veterans Affairs Medical Center - White River Junction White River Junction Vermont United States 05009
    73 Martha Jefferson Hospital Charlottesville Virginia United States 22902
    74 Virginia Oncology Associates - Norfolk Norfolk Virginia United States 23502
    75 MBCCOP - Massey Cancer Center Richmond Virginia United States 23298-0037
    76 Oncology and Hematology Associates of Southwest Virginia, Inc. Roanoke Virginia United States 24014
    77 St. Mary's Medical Center Huntington West Virginia United States 25701
    78 University of Puerto Rico School of Medicine Medical Sciences Campus San Juan Puerto Rico 00936-5067

    Sponsors and Collaborators

    • Alliance for Clinical Trials in Oncology
    • National Cancer Institute (NCI)

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Alliance for Clinical Trials in Oncology
    ClinicalTrials.gov Identifier:
    NCT00006265
    Other Study ID Numbers:
    • CALGB-19902
    • U10CA031946
    • CALGB-19902
    • CDR0000068208
    First Posted:
    Sep 3, 2003
    Last Update Posted:
    Jul 14, 2016
    Last Verified:
    Jul 1, 2016
    Keywords provided by Alliance for Clinical Trials in Oncology
    recurrent adult acute myeloid leukemia
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Cytarabine
    Gemtuzumab

    Study Results

    No Results Posted as of Jul 14, 2016