Antithymocyte Globulin and Cyclosporine in Treating Patients With Myelodysplastic Syndrome

Study Overview
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Brief Summary
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The main objective of this trial is to evaluate the efficacy and toxicity of intensive immuno-suppression with ATG + CSA versus best supportive care in patients with transfusion dependent low and intermediate risk myelodysplastic syndrome (MDS).

Detailed Description
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This trial will answer the question whether immuno-suppression improves hematopoesis and reduces transfusion requirements analogous to patients with aplastic anemia as the short-term outcome, and whether immuno-suppression accelerates leukemic transformation and influences survival as the long-term outcome. Primary endpoint: best response (CR + PR) rate at month 6

Official Title
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Antithymocyte Globulin (ATG) and Cyclosporine (CSA) to Treat Patients With Myelodysplastic Syndrome (MDS). A Randomized Trial Comparing ATG + CSA With Best Supportive Care

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: ATG + CSA
* Behavioral: Supportive care


Participation Criteria
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Eligibility Criteria
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Hypoplastic MDS, or MDS subtype RA, RAS or RAEB with ≤ 10% blasts, or RAEB with 10-20% blasts and the patient refusing or not eligible for the MDS high risk protocol (EORTC 06961) Transfusion dependence < 24 months or neutrophils < 0.5 × 109/l. ECOG/SAKK performance status ≤ 2 Age > 18 years No active uncontrolled infection No prior chemotherapy or radiotherapy No history of heart failure, clinically relevant cardiac arrhythmia or other hemato-oncological disease

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A: ATG + CSA<br>Treatment consists of 15 mg/kg ATG (Mérieux; horse antithymocyte globulin; i.e. 1.5 vial/10 kg of body weight/day) given over 8-12 hours for 5 consecutive days. Cyclosporine A (CSA) will be administered orally in a dose of 2.5 mg/kg bid starting day 1 and continued through day 180. | Drug: ATG + CSA<br>* Mérieux; horse antithymocyte globulin (ATG) + Cyclosporine A (CSA)<br>|
| Other: Arm B: Supportive care<br>Patients randomized to this arm will be treated as outpatients. | Behavioral: Supportive care<br>* Patients randomized to this arm will be treated as outpatients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response rate (CR + PR) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate at month 3, time to response, quality and duration of response, and proportions of relapse/progression in responders |  | 2 and 5 years after first response | 
| Overall survival |  | 2 and 5 years | 
| Leukemia-free survival |  | 2 and 5 years | 
| Transformation-free survival |  | 2 and 5 years | 

 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, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes