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

NCT ID: NCT00001839

Last Updated: 2008-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 182 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-12-31
• Study Completion Date: 2000-05-31

Brief Summary

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.

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.

Conditions

Hematologic Diseases; Myelodysplastic Syndromes

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Antithymocyte globulin

Intervention Type: DRUG

Cyclosporine

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Locations

Warren G. Magnuson Clinical Center (CC)

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

99-CC-0021

Identifier Type: -

Identifier Source: secondary_id

990021

Identifier Type: -

Identifier Source: org_study_id