Antithymocyte Globulin Compared With Supportive Care in Treating Patients With Myelodysplastic Syndrome

January 24, 2021 updated by: Genzyme, a Sanofi Company

An Open Label, Prospective, Stratified, Randomized, Controlled, Multi-Center, Phase IIB Study of the Impact of Thymoglobulin Therapy on Transfusion Needs of Patients With Early Myelodysplastic Syndrome (MDS)

RATIONALE: Immunosuppressive therapy may improve bone marrow abnormalities and may be effective treatment for myelodysplastic syndrome. It is not yet known whether immunosuppressive therapy is more effective than supportive care in treating myelodysplastic syndrome.

PURPOSE: Randomized phase II trial to compare the effectiveness of antithymocyte globulin with that of supportive care in treating patients who have myelodysplastic syndrome.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the clinical response rate of patients with early myelodysplastic syndrome treated with rabbit anti-thymocyte globulin vs standard supportive care.
  • Evaluate the safety of anti-thymocyte globulin in these patients.
  • Compare the time to and duration of clinical response, rates of partial response and therapy failure, and rate of disease progression in patients treated with these regimens.
  • Compare the ECOG performance score, number of transfusions and/or growth factor use, and maximum time between transfusions in patients treated with these regimens.
  • Compare the infection risk, use of medical resources, and quality of clinical response in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to myelodysplastic syndrome (MDS) subtype (refractory anemia (RA) vs RA with excess blasts or hypocellular MDS). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive rabbit anti-thymocyte globulin (ATG) IV over at least 8-12 hours on days 1-4.
  • Arm II: Patients receive standard supportive therapy for 6 months. At the end of 6 months, patients may receive ATG as in arm I.

Patients are followed for 6 months.

PROJECTED ACCRUAL: A total of 72 patients (48 in arm I and 24 in arm II) will be accrued within a minimum of 6 months.

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

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Foothills Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E3
        • Department of Medicine
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Washington Cancer Institute
    • Florida
      • Gainesville, Florida, United States, 32610-0296
        • University of Florida Health Science Center
      • Miami, Florida, United States, 33136
        • Sylvester Cancer Center, University of 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)
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush Cancer Institute
    • Indiana
      • Beech Grove, Indiana, United States, 46107
        • Indiana Blood and Marrow Transplant
    • Iowa
      • Iowa City, Iowa, United States, 52242-1009
        • Holden Comprehensive Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • University of Kansas Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University School of Medicine
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • University of Missouri Kansas City School of Medicine
      • Saint Louis, Missouri, United States, 63110
        • Siteman Cancer Center
      • Saint Louis, Missouri, United States, 63110-2539
        • Saint Louis University Cancer Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • University of Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10021
        • New York Presbyterian Hospital - Cornell Campus
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center, NY
      • Rochester, New York, United States, 14642
        • James P. Wilmot Cancer Center
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Comprehensive Cancer Center at Wake Forest University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
    • Texas
      • Dallas, Texas, United States, 75230-2503
        • Texas Oncology P.A.
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226-3596
        • Medical College of Wisconsin

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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed early myelodysplastic syndrome (MDS) with less than 10% bone marrow blasts

    • Refractory anemia (RA)
    • RA with excess blasts (RAEB)
    • Hypocellular myelodysplasia
  • Low or intermediate-1 prognostic risk

  • Transfusion-dependent

    • Need for 2 or more units of red blood cells or platelets per month for 2 or more months prior to study OR

    • History of prior transfusions and 2 consecutive (at least 21 days apart) hemoglobin levels less than 8.0 g/dL or platelet counts less than 20,000/mm^3 during the past 2 months

      • Hemoglobin no greater than 12.0 g/dL after prior transfusion
  • No myelosclerosis occupying more than 30% of bone marrow space
  • No RA with ringed sideroblasts, RAEB in transformation, or chronic myelomonocytic leukemia
  • No therapy-related MDS
  • No history of immune-related hematologic disorder (e.g., idiopathic thrombocytopenic purpura)

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 3 months

Hematopoietic:

  • See Disease Characteristics
  • No other causes of cytopenia unrelated to MDS (e.g., gastrointestinal blood loss)
  • Iron present on marrow examination OR
  • Transferrin saturation at least 20% and ferritin at least 50 ng/mL

Hepatic:

  • Bilirubin no greater than 2 mg/dL OR
  • SGOT/SGPT no greater than 2 times normal
  • No active or chronic hepatitis B or C

Renal:

  • Creatinine no greater than 2 mg/dL

Cardiovascular:

  • No symptomatic cardiac disease
  • No congestive heart failure (even if medically controlled)
  • No myocardial infarction within the past 6 months

Pulmonary:

  • No severe pulmonary disease
  • If history of pulmonary insufficiency, must have pO_2 at least 90 mm/Hg on room air or pCO_2 no greater than 40 mm/Hg

Other:

  • No history of unresolved B12 or folate deficiency since diagnosis of MDS
  • No untreated acute or chronic infection (afebrile for 7 days without antibiotics prior to study)
  • No active or chronic HIV
  • No concurrent cytomegalovirus infection
  • No other malignancy within the past 2 years except adequately treated localized squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
  • No concurrent drug or alcohol abuse
  • No significant medical or psychosocial problems
  • No known allergy to rabbit protein
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 8 weeks since prior biologic agents, colony-stimulating factors, or epoetin alfa for MDS
  • At least 8 weeks since other prior investigational biologic agents
  • No prior or concurrent bone marrow transplantation
  • No concurrent epoetin alfa
  • No concurrent growth factors except filgrastim (G-CSF) or sargramostim (GM-CSF) for neutropenic fevers
  • No other concurrent biologic agents

Chemotherapy:

  • At least 8 weeks since prior cytotoxic drugs for MDS
  • Concurrent chemotherapy for clinical indications of disease progression or leukemic transformation allowed

Endocrine therapy:

  • At least 8 weeks since prior androgenic hormonal therapy for MDS
  • At least 8 weeks since prior danazol for MDS

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • No prior organ transplantation

Other:

  • At least 8 weeks since prior investigational drugs
  • At least 8 weeks since prior immunosuppressive drugs or other drugs for MDS
  • No concurrent immunosuppressive therapy
  • No other concurrent experimental drugs

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
  • Masking: None (Open Label)

Collaborators and Investigators

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

Sponsor

Genzyme, a Sanofi Company

Investigators

  • Study Chair: Elizabeth C. Squiers, MD, Sangstat Medical Corporation

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)

September 1, 2000

Primary Completion (Actual)

November 1, 2003

Study Completion (Actual)

November 1, 2003

Study Registration Dates

First Submitted

June 6, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

January 27, 2021

Last Update Submitted That Met QC Criteria

January 24, 2021

Last Verified

March 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000068709
  • SMC-101-1020
  • RUSH-MDS-2000-04

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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