Antithymocyte Globulin and Cyclosporine to Treat Myelodysplasia

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00005937
First received: July 6, 2000
Last updated: March 26, 2010
Last verified: December 2009
  Purpose

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: 1) evaluate whether this drug combination can increase blood counts in patients and reduce their need for transfusions; 2) compare survival of patients who respond to ATG and cyclosporine treatment with those who do not respond; and 3) 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). For this procedure, the hip area is anesthetized and a special needle is used to draw marrow from the bone.

Participants will be admitted to the NIH Clinical Center for the first 10 days of treatment and will then continue therapy on an outpatient basis. They will undergo the following tests and procedures:

  • Placement of central line-An intravenous (IV) catheter (flexible tube inserted into a vein) is placed in a large vein of the neck, chest or arm. Medicines are delivered through this line and blood samples are drawn from it.
  • ATG skin testing-ATG is injected under the skin to check for sensitization to horse serum, from which the drug is derived.
  • ATG treatment-Four doses of ATG are given through the IV line on each of 4 consecutive days. Prednisone is taken by mouth beginning the first day of ATG therapy and continuing for a total of 17 days. This drug is given to reduce the side effects of ATG, such as fever, skin rash and chills.
  • Cyclosporine treatment-Cyclosporine capsules are taken by mouth twice a day for at least 6 months.

During hospitalization, blood will be drawn daily for blood counts and other tests. Upon the patient's discharge after 10 days, the referring physician will do blood tests weekly during the first month of treatment and then every 2 weeks for the rest of the time the patient is taking cyclosporine. Dosages of this drug may be adjusted depending on the test results. Patients will be evaluated at the NIH Clinical Center at 3-month intervals for the first year, then every 6 months for the next 3 years and then at yearly intervals. A blood sample will be drawn at each visit. Bone marrow biopsies will be done at 6-month intervals for the first 3 years after treatment.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Antithymocyte globulin
Drug: Cyclosporine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Antithymocyte Globulin (ATG) and Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Transfusion-independence [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: June 2000
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Antithymocyte globulin
    N/A
    Drug: Cyclosporine
    N/A
Detailed Description:

A growing body of laboratory and clinical evidence suggests that the cytopenia of MDS is at least partly a result of cytotoxic T cell activity. Treatments to abrogate T cell activity such as anti-thymocyte globulin alone and cyclosporine alone have demonstrated varying degrees of success in alleviating the cytopenia of MDS. A response to such therapy in MDS is associated with improved survival. Experience with aplastic anemia suggests that the combination of these two agents should be more effective in suppressing cytotoxic T cell activity and alleviating cytopenia. This protocol proposes using the combination of antithymocyte globulin (ATG) and cyclosporine (CSA) to treat the cytopenia of MDS, in an effort to improve the response rate to immunosuppressive therapy in this disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

MDS of RA, RARS & RAEB sub-types

Off all other treatments (except G-CSF, 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.

ECOG performance status of 2 or less

High or intermediate predcted 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-SCF) 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

  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: NCT00005937

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Additional Information:
Publications:
Responsible Party: Elaine M. Sloand, M.D./National Heart, Lung, and Blood Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00005937     History of Changes
Other Study ID Numbers: 000169, 00-H-0169
Study First Received: July 6, 2000
Last Updated: March 26, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
MDS
Immunosuppression
ATG
Cyclosporine
Myelodysplastic Syndrome

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
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 October 19, 2014