Safety and Efficacy of Azacitidine, and Thalidomide in Higher Risk MDS (Myelodysplastic Syndrome)

Summary

Study Objectives The aim of the study is to evaluate the safety and efficacy of the combination of 5-Aza-Cytidine + Thalidomide on the course of hrMDS patients. Primary end point: • To evaluate the overall response rate (CR+PR) of the combination of 5-Aza-Cytidine + Thalidomide in hrMDS patients (INT-2 and High risk as defined by IPSS). Secondary end points: * To evaluate the safety of the combination of Thalidomide+5-Aza-Cytidine in high risk MDS patients. * Hematological improvement rate. * Cytogenetic response. * Progression free survival (PFS). * Quality of life assessment (FACT: MDS and peripheral neuropathy QOL Questionnaires). Study design: This is a multicenter, phase II, single arm study designed to evaluate the safety and efficacy of the combination of Thalidomide+5-Aza-Cytidine in high risk MDS patients (INT-2 and High risk defined by IPSS) who are older than 18 years of age. Potential study subjects will sign an informed consent prior to undergoing any study related procedure. Number of patients to be enrolled 50. Treatment plan: 5-aza-cytidine (75 mg m2/d) will be injected subcutaneously in 5-day cycle every 28 days, for a total of 12 cycles. Thalidomide will be given at the dose of 50 mg/d, from day 1 until for 6 months together with 5-aza-cytidine . Treatment period includes 5-aza-cytidine (75 mg m2/d) will be injected subcutaneously in 5-day cycle every 28 days. Total number of 12 cycles or until progression or toxicity. Cycle delay of maximum 2 weeks in case of hematological toxicity grade 3-4 at investigator discretion. Duration of the follow up period is 6 months. Duration of study The duration of the treatment period is approximately 12 months. This time is required to complete the treatment, and to determine the safety profile and the response rate. The duration of the Follow period will be approximately a half year. The occurrence of PD will determine the duration of progression-free survival of each patient.

Timeline

Start

2008-09

Primary completion

2010-09

Completion

2011-04

Publications

• Background 1. Greenberg PL. Risk factors and their relationship to prognosis in myelodysplastic syndromes. Leuk Res. 1998;22 Suppl 1:S3-6. 2. Sanz GF, Sanz MA, Greenberg PL. Prognostic factors and scoring systems in myelodysplastic syndromes. Haematologica. 1998;83:358-368. 3. Hellstrom-Lindberg E, Ahlgren T, Beguin Y, et al. Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood. 1998;92:68-75. 4. Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20:2429-2440. 5. Silverman LR, McKenzie DR, Peterson BL, et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol. 2006;24:3895-3903. 6.

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Indications