Antithymocyte Globulin and Cyclosporine to Treat Myelodysplasia
Condition: Myelodysplastic Syndrome
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Antithymocyte globulin; Cyclosporine
Intervention description: Antithymocyte globulin (ATG) intravenous infusion: 40mg/kg/day. Infusion over 6 hours on day 1-4.; Cyclosporine (CsA) intravenous infusion: 5mg/kg. Infusion on day 14 administered twice a day.
Intervention MeSH terms: Cyclosporine; Cyclosporins; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MDS; Immunosuppression; ATG; Cyclosporine; Myelodysplastic Syndrome

Summary:

      This study will determine the safety and effectiveness of a combination of the
      immune-suppressing drugs antithymocyte globulin (ATG) and cyclosporine for treating
      myelodysplasia, a disorder of low blood cell counts. It will: evaluate whether this drug
      combination can increase blood counts in patients and reduce their need for transfusions;
      compare survival of patients who respond to ATG and cyclosporine treatment with those who do
      not respond; and determine the side effects of the treatment.

      Myelodysplasia is thought to result from an immune system abnormality in which cells called
      lymphocytes attack the marrow's blood-forming cells. The resulting deficiencies of platelets
      and red and white blood cells cause anemia, susceptibility to infections, and easy bruising
      and bleeding. Various therapies, such as blood transfusions for anemia and bleeding,
      antibiotics for infection, chemotherapy and bone marrow transplantation are used to treat
      myelodysplasia, but all have disadvantages and some carry serious risks.

      Patients 18 years of age and older with myelodysplasia may be eligible for this study.
      Candidates will be screened with a physical examination and medical history, blood tests,
      chest X-ray, electrocardiogram and bone marrow biopsy (removal of a marrow sample from the
      hipbone for microscopic examination).
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  MDS of refractory anemia (RA), refractory anemia with ring sideroblasts (RARS) &
             refractory anemia with excess blasts (RAEB) sub-types

          -  Off all other treatments (except G-CSF (granulocyte colony stimulating factor), and
             transfusion support and related medications) for at least four weeks.

          -  G-CSF can be used before, during and after the protocol treatment for patients with
             documented neutropenia (less than 500/uL) as long as they meet the criteria for anemia
             and/or thrombocytopenia as stated above.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

          -  High or intermediate predicted probability of response

        EXCLUSION CRITERIA:

          -  MDS of FAB sub-group chronic myelomonocytic leukemia (CMML)

          -  Transformation to acute leukemia (FAB sub-group RAEB-T, ie., greater than 20% blasts
             in marrow aspirate)

          -  Hypoplastic marrow without one major or two minor criteria

          -  Treatment with growth factors (except for G-CSF) or cyclosporine within 4 weeks prior
             to entry to protocol

          -  ECOG performance status of greater than 2

          -  Active uncontrolled infection

          -  Current pregnancy, or unwilling to take oral contraceptives if of childbearing
             potential

          -  Patients for whom bone marrow transplant is indicated as standard therapy (age less
             than fifty-five with a fully-matched sibling donor)

          -  Age less than18 years

          -  Not able to give informed consent

          -  HIV positive patients

          -  Active malignant disease (excluding basal cell carcinoma)

          -  Serum creatinine greater than 2mg/dl

          -  Patients who are moribund or patients with concurrent hepatic, renal, cardiac,
             metabolic, or any disease of such severity that death within 3 months is likely

          -  Low predicted probability of response