A Randomized Trial of Antithymocyte Globulin Versus Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001839
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: December 1998
  Purpose

Approximately 40% of the patients with myelodysplastic syndrome (MDS) die as a consequence of their cytopenia. As in aplastic anemia, the cytopenia of MDS may be partly due to cytotoxic T cell activity. Immunosuppressive therapy may therefore reverse the cytopenia. In a phase II pilot study of anti-thymocyte globin (ATG) to treat myelodysplastic syndrome (MDS); 41% of patients (61% of patients with refractory anemia) have responded in terms of transfusion independence. Recently, Jonasova et al [32] reported a 82% substantial hematological response rate in 18 patients with MDS of the refractory anemia (RA) subtype treated with cyclosporine alone. Just over 50% of the patients in this series had MDS of the hypocellular type. Cyclosporine alone if indeed efficacious would be a powerful therapeutic option that could be readily used by hematologists in the community to treat patients with MDS. This efficacy needs to be proven in a larger study which includes patients with the other subtypes of MDS and more patients with the non-hypocellular forms of MDS (which constitute approximately 70% of the cases in the community). As MDS is a heterogeneous group of disorders, a randomized comparison with the other immunomodulating intervention of proven benefit, ATG, is appropriate. In this randomized study patients with MDS will receive either ATG alone or cyclosporine alone.


Condition Intervention Phase
Hematologic Diseases
Myelodysplastic Syndromes
Drug: Antithymocyte globulin
Drug: Cyclosporine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: A Randomized Trial of Antithymocyte Globulin Versus Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 182
Study Start Date: December 1998
Estimated Study Completion Date: May 2000
Detailed Description:

Approximately 40% of the patients with myelodysplastic syndrome (MDS) die as a consequence of their cytopenia. As in aplastic anemia, the cytopenia of MDS may be partly due to cytotoxic T cell activity. Immunosuppressive therapy may therefore reverse the cytopenia. In a phase II pilot study of anti-thymocyte globulin (ATG) to treat myelodysplastic syndrome (MDS); 41% of patients (61% of patients with refractory anemia) have responded in terms of transfusion independence. Recently, Jonasova et al [32] reported a 82% substantial hematological response rate in 18 patients with MDS of the refractory anemia (RA) subtype treated with cyclosporine alone. Just over 50% of the patients in this series had MDS of the hypocellular type. Cyclosporine alone if indeed efficacious would be a powerful therapeutic option that could be readily used by hematologists in the community to treat patients with MDS. This efficacy needs to be proven in a larger study which includes patients with the other subtypes of MDS and more patients with the non-hypocellular forms of MDS (which constitute approximately 70% of the cases in the community). As MDS is a heterogeneous group of disorders, a randomized comparison with the other immunomodulating intervention of proven benefit, ATG, is appropriate. In this randomized study patients with MDS will receive either ATG alone or cyclosporine alone.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

MDS of RA & RAEB sub-types.

No current treatment and off other treatments for at least two weeks.

ECOG performance status less than or equal to 2.

No MDS of FAB sub-group' refractory anemia with ring sideroblasts' (RARS).

No transforming to acute leukemia (FAB sub-group RAEB-Tie.; greater than 20% blasts in marrow aspirate).

No hypoplastic marrow without one major or two minor criteria as outlined in table 3 of the appendix.

No one being treatment with growth factors or cyclosporine within four weeks prior to entry to protocol.

No previous treatment with ATG.

No ECOG performance status of greater than 2.

No active uncontrolled infection.

No women which current pregnancy, or unwilling to take oral contraceptives if of childbearing potential.

No patients for whom bone marrow transplant is indicated as primary therapy.

No one age less than 18 years.

Must be able to give informed consent.

No HIV positive patients.

No active malignant disease (excluding basal cell carcinoma).

No one with serum creatine greater than 2mg/dl.

No patients who are moribund or patients with concurrent hepatic, renal, cardiac, metabolic, or any disease of such severity that death within 7-10 days is likely.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001839

Locations
United States, Maryland
Warren G. Magnuson Clinical Center (CC)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00001839     History of Changes
Other Study ID Numbers: 990021, 99-CC-0021
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Anemia
Immunosuppressive
Phase II Trial
Pre-Leukemia
Therapy
Myelodysplastic Syndrome

Additional relevant MeSH terms:
Hematologic Diseases
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Precancerous Conditions
Neoplasms
Antilymphocyte Serum
Cyclosporins
Cyclosporine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014