Antithymocyte Globulin and Cyclosporine in Treating Patients With Myelodysplastic Syndrome

Sponsor

Swiss Group for Clinical Cancer Research (Other)

Overall Status

Completed

CT.gov ID

NCT00004208

Collaborator

(none)

Enrollment

Location

Arms

134

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: ATG + CSA Behavioral: Supportive care	Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

86 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2000

Actual Primary Completion Date :

Oct 1, 2006

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: ATG + CSA 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 Mérieux; horse antithymocyte globulin (ATG) + Cyclosporine A (CSA)
Other: Arm B: Supportive care Patients randomized to this arm will be treated as outpatients.	Behavioral: Supportive care Patients randomized to this arm will be treated as outpatients.

Arm

Intervention/Treatment

Active Comparator: Arm A: ATG + CSA

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

Mérieux; horse antithymocyte globulin (ATG) + Cyclosporine A (CSA)

Other: Arm B: Supportive care

Patients randomized to this arm will be treated as outpatients.

Behavioral: Supportive care

Patients randomized to this arm will be treated as outpatients.

Outcome Measures

Primary Outcome Measures

Best response rate (CR + PR) [6 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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