Comparison of Three Treatment Regimens in Treating Patients With Relapsed or Refractory Acute Myelogenous Leukemia

June 20, 2023 updated by: Eastern Cooperative Oncology Group

A Phase II Randomized Trial of Immunologic and Chemotherapeutic Agents for Treatment of Patients With Relapsed or Refractory Acute Myelogenous Leukemia

RATIONALE: Drugs used in chemotherapy use 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 more than one drug or combining monoclonal antibody with chemotherapy may kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia.

PURPOSE: Randomized phase II trial to compare the effectiveness of three treatment regimens in treating patients who have relapsed or refractory acute myelogenous leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the rates of complete response (CR) and CR without full platelet recovery in patients with relapsed or refractory acute myelogenous leukemia treated with gemtuzumab ozogamicin and cytarabine vs daunorubicin liposomal and cytarabine vs cyclophosphamide, cytarabine, and topotecan.
  • Compare the toxicities of these 3 regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by disease status (relapse less than 6 months after first complete response (CR) vs relapse 6-12 months after first CR vs refractory to conventional initial induction chemotherapy (no more than 2 courses) or first reinduction (no more than 1 course) vs second or greater relapse).

  • Induction: Patients are randomized to 1 of 3 treatment arms:

    • Arm I: Patients receive cytarabine IV over 2 hours on days 1-4 and gemtuzumab ozogamicin IV over 2 hours on day 5.
    • Arm II: Patients receive daunorubicin liposomal IV over a minimum of 2 hours on days 1-3 and cytarabine IV over 2 hours (beginning immediately after completion of daunorubicin liposomal infusion) on days 1-4.
    • Arm III: Patients receive cyclophosphamide IV over 1 hour every 12 hours on days 1-3, cytarabine IV over 2 hours (beginning immediately after completion of cyclophosphamide infusion) on days 2-6, and topotecan IV continuously on days 2-6.
  • Consolidation: Patients who achieve complete remission (CR) receive 1 additional course of induction therapy on the same arm to which they were originally randomized beginning within 4-6 weeks after initial documentation of CR. Patients on arm II receive no additional daunorubicin liposomal if resting ejection fraction is less than 50% preconsolidation. All patients receive sargramostim (GM-CSF) IV over 4 hours or SQ daily beginning 24 hours after completion of consolidation therapy and continuing until blood counts recover.

Patients are followed every 3 months through year 2, every 6 months through year 5, and then annually thereafter until death.

PROJECTED ACCRUAL: A maximum of 150-165 patients (50-55 per arm) will be accrued for this study within 2 years.

Study Type

Interventional

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, 00927-5800
        • MBCCOP - San Juan
      • San Juan, Puerto Rico, 00927-5800
        • Veterans Affairs Medical Center - San Juan
  • South Africa
      • Pretoria, South Africa, 0001
        • Pretoria Academic Hospitals
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259-5404
        • CCOP - Scottsdale Oncology Program
    • California
      • Duarte, California, United States, 91010-3000
        • Cancer Center and Beckman Research Institute, City of Hope
      • Palo Alto, California, United States, 94304
        • Veterans Affairs Medical Center - Palo Alto
      • Stanford, California, United States, 94305-5408
        • Stanford University Medical Center
    • Colorado
      • Denver, Colorado, United States, 80209-5031
        • CCOP - Colorado Cancer Research Program, Inc.
    • Delaware
      • Wilmington, Delaware, United States, 19899
        • CCOP - Christiana Care Health Services
    • Florida
      • Gainesville, Florida, United States, 32608-1197
        • Veterans Affairs Medical Center - Gainsville
      • Miami, Florida, United States, 33125
        • Veterans Affairs Medical Center - Miami
      • Tampa, Florida, United States, 33612-9497
        • H. Lee Moffitt Cancer Center and Research Institute
      • Tampa, Florida, United States, 33612
        • Veterans Affairs Medical Center - Tampa (Haley)
    • Illinois
      • Chicago, Illinois, United States, 60611-3013
        • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
      • Chicago, Illinois, United States, 60611
        • Veterans Affairs Medical Center - Lakeside Chicago
      • Decatur, Illinois, United States, 62526
        • CCOP - Central Illinois
      • Evanston, Illinois, United States, 60201
        • CCOP - Evanston
      • Peoria, Illinois, United States, 61602
        • CCOP - Illinois Oncology Research Association
      • Urbana, Illinois, United States, 61801
        • CCOP - Carle Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Indiana University Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Veterans Affairs Medical Center - Indianapolis (Roudebush)
    • Iowa
      • Cedar Rapids, Iowa, United States, 52403-1206
        • CCOP - Cedar Rapids Oncology Project
      • Des Moines, Iowa, United States, 50309-1016
        • CCOP - Iowa Oncology Research Association
      • Iowa City, Iowa, United States, 52242-1009
        • Holden Comprehensive Cancer Center at the University of Iowa
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • CCOP - Ochsner
      • New Orleans, Louisiana, United States, 70112
        • MBCCOP - LSU Health Sciences Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02111
        • New England Medical Center Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • CCOP - Ann Arbor Regional
      • Kalamazoo, Michigan, United States, 49007-3731
        • CCOP - Kalamazoo
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • CCOP - Duluth
      • Minneapolis, Minnesota, United States, 55417
        • Veterans Affairs Medical Center - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
      • Saint Louis Park, Minnesota, United States, 55416
        • CCOP - Metro-Minnesota
    • Nebraska
      • Omaha, Nebraska, United States, 68131
        • CCOP - Missouri Valley Cancer Consortium
      • Omaha, Nebraska, United States, 68105
        • Veterans Affairs Medical Center - Omaha
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • CCOP - Southern Nevada Cancer Research Foundation
    • New Jersey
      • East Orange, New Jersey, United States, 07018-1095
        • Veterans Affairs Medical Center - East Orange
      • Hackensack, New Jersey, United States, 07601
        • CCOP - Northern New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Cancer Institute of New Jersey
    • New York
      • Bronx, New York, United States, 10461
        • Albert Einstein Comprehensive Cancer Center
      • Bronx, New York, United States, 10466
        • MBCCOP-Our Lady of Mercy Cancer Center
      • Brooklyn, New York, United States, 11209
        • Veterans Affairs Medical Center - Brooklyn
      • New York, New York, United States, 10016
        • NYU School of Medicine's Kaplan Comprehensive Cancer Center
      • New York, New York, United States, 10010
        • Veterans Affairs Medical Center - New York
      • Rochester, New York, United States, 14642
        • University of Rochester Cancer Center
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • CCOP - Merit Care Hospital
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
      • Cleveland, Ohio, United States, 44106-5065
        • Ireland Cancer Center
      • Columbus, Ohio, United States, 43206
        • CCOP - Columbus
      • Toledo, Ohio, United States, 43623-3456
        • CCOP - Toledo Community Hospital Oncology Program
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • CCOP - Oklahoma
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19102-1192
        • Hahnemann University Hospital
      • Philadelphia, Pennsylvania, United States, 19104-4283
        • University of Pennsylvania Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107-5541
        • Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213-3489
        • University of Pittsburgh Cancer Institute
      • Pittsburgh, Pennsylvania, United States, 15240
        • Veterans Affairs Medical Center - Pittsburgh
      • Wynnewood, Pennsylvania, United States, 19096
        • CCOP - MainLine Health
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • CCOP - Sioux Community Cancer Consortium
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Comprehensive Cancer Center
      • Madison, Wisconsin, United States, 53705
        • Veterans Affairs Medical Center - Madison
      • Marshfield, Wisconsin, United States, 54449
        • CCOP - Marshfield Medical Research and Education Foundation

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • Histologically proven acute myelogenous leukemia of one of the following types:

    • Acute myeloblastic leukemia (FAB type M0, M1, or M2)
    • Acute promyelocytic leukemia (FAB type M3) allowed if ineligible for an ECOG M3 protocol or if no tretinoin or arsenic trioxide therapy is planned
    • Acute myelomonocytic leukemia (FAB type M4)
    • Acute monocytic leukemia (FAB type M5)
    • Acute erythroleukemia (FAB type M6)
    • Acute megakaryocytic leukemia (FAB type M7)

  • Must meet 1 of the following criteria:

    • Relapse less than 6 months after first complete remission (CR)
    • Relapse 6-12 months after first CR

    • Refractory to conventional initial induction chemotherapy (no more than 2 courses) or first reinduction (no more than 1 course)

      • Must have marrow documentation of residual leukemia after chemotherapy (for at least 2 weeks duration)
    • Second or greater relapse
  • No relapse greater than 1 year after achieving first CR
  • Blast cells must be CD33 positive
  • Prior CNS leukemia allowed if there is currently documentation of no CNS involvement on CSF examination (i.e., negative CSF by lumbar puncture)

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL*
  • SGOT less than 2 times upper limit of normal* NOTE: *Unless due to leukemia infiltration

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • See Chemotherapy
  • No myocardial infarction within the past 3 months
  • No significant congestive heart failure
  • No significant cardiac arrhythmia
  • Cardiac ejection fraction normal by MUGA scan or echocardiogram
  • Resting ejection fraction at least 50% or at least 5% increase with exercise
  • Shortening fraction at least 24% or normal by echocardiogram

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No concurrent organ damage or other medical problems that would precludestudy therapy
  • No concurrent evidence (including positive blood or deep tissue cultures or stains) of invasive fungal infection
  • No hypersensitivity to ingredients of gemtuzumab ozogamicin or daunorubicin liposomal
  • No other active tumor that would interfere with study therapy or increase risk

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior gemtuzumab ozogamicin

Chemotherapy:

  • See Disease Characteristics
  • See Biologic therapy
  • No prior daunorubicin liposomal or topotecan
  • Prior doxorubicin (no greater than 300 mg/m2), daunorubicin (no greater than 300 mg/m2), idarubicin (no greater than 100 mg/m2), or mitoxantrone (no greater than 100 mg/m2) allowed if left ventricular function is adequate
  • At least 4 weeks since prior chemotherapy except patients who are refractory to conventional initial induction chemotherapy
  • Prior hydroxyurea allowed within 4 weeks prior to beginning study
  • Hydroxyurea must be discontinued at least 24 hours prior to beginning study

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 4 weeks since prior radiotherapy except patients who are refractory to conventional initial induction chemotherapy

Surgery:

  • Not specified

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: Randomized

Collaborators and Investigators

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

Sponsor

Eastern Cooperative Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Mark R. Litzow, MD, Mayo Clinic

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 (Actual)

October 4, 2000

Primary Completion (Actual)

October 1, 2005

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

July 5, 2000

First Submitted That Met QC Criteria

November 4, 2003

First Posted (Estimated)

November 5, 2003

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

June 20, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000067944
  • E-4999

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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