S0020 Immunosuppressive Therapy in Treating Patients With Myelodysplastic Syndrome

Study Overview
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Brief Summary
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RATIONALE: Immunosuppressive therapy may improve bone marrow abnormalities and may be an effective treatment for myelodysplastic syndrome. PURPOSE: Phase II trial to study the effectiveness of antithymocyte globulin plus cyclosporine in treating patients who have myelodysplastic syndrome.

Detailed Description
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OBJECTIVES: Determine the response in patients with myelodysplastic syndromes treated with anti-thymocyte globulin and cyclosporine. Determine the frequency and severity of toxic effects of this regimen in these patients. Assess the correlation between response to treatment and the in vitro assessment of T-lymphocyte subsets in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to myelodysplastic syndrome subclassification (refractory anemia [RA] vs RA with ringed sideroblasts vs RA with excess blasts). Patients receive induction therapy comprising anti-thymocyte globulin IV over 6-12 hours on days 1-4 and oral cyclosporine twice daily on days 5-94 followed by a taper until day 124. Patients who relapse after a response of at least 60 days may receive reinduction therapy comprising oral cyclosporine twice daily on days 1-90 followed by a taper until day 120. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for 6 months, every 2 months for 2 years, and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 130 patients (53 with refractory anemia [RA], 33 with RA with ringed sideroblasts, and 44 with RA with excess blasts) will be accrued for this study within 14-22 months.

Official Title
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A Phase II Study of Anti-Thymocyte Globulin and Cyclosporine for Patients With Myelodysplastic Syndrome (MDS)

Conditions
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Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Biological: anti-thymocyte globulin
* Drug: cyclosporine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Morphologically confirmed myelodysplastic syndromes (MDS) Refractory anemia (RA) RA with ringed sideroblasts RA with excess blasts Low, intermediate-1, or intermediate-2 risk by International Prognostic Scoring System criteria MDS secondary to prior chemotherapy and/or radiotherapy for other malignant disorders allowed Must have received prior transfusions of at least 4 units of red blood cells for anemia within the past 60 days Must be concurrently registered on SWOG-S9910 and SWOG-9007 Ineligible for or refused participation in SWOG-S9920 (HLA-identical sibling peripheral blood stem cell transplantation) PATIENT CHARACTERISTICS: Age: 15 and over Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission HIV negative Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Prior cytokines (e.g., interferon or interleukin), colony-stimulating factors, or epoetin alfa allowed No prior bone marrow or stem cell transplantation No concurrent growth factors (including epoetin alfa) except filgrastim (G-CSF) or sargramostim (GM-CSF) for neutropenia Chemotherapy: See Disease Characteristics No prior remission induction chemotherapy for MDS Prior hydroxyurea allowed Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics Surgery: Not specified Other: Prior amifostine allowed No calcium-channel blockers (diltiazem, nicardipine, or verapamil), antifungals (fluconazole, itraconazole, or ketoconazole), antibiotics (clarithromycin or erythromycin), or other drugs (bromocriptine or danazol) that would increase cyclosporine concentrations for 48 hours before, during, and for 48 hours after cyclosporine No antibiotics (nafcillin or rifampin) or anticonvulsants (carbamazepine, phenobarbital, or phenytoin) that would decrease cyclosporine concentrations for 14 days before and during cyclosporine

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: anti-thymocyte globulin|3.5 mg/kg/d IV over 12 hrs day 1|
|Drug: cyclosporine|3 mg/kg bid days 5-94 then taper to 0 at day 124 PO|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total response |  | after induction therapy is completed | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, de novo myelodysplastic syndromes, secondary myelodysplastic syndromes, childhood myelodysplastic syndromes