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There are limited therapeutic options available for these diseases, and single agents have only modest efficacy. In this phase 2 study, the authors combined multiple active agents (thalidomide, arsenic trioxide, dexamethasone, and ascorbic acid [TADA]) to treat patients with these disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>This multicenter trial was conducted from January 2005 to July 2007. The primary endpoint was to evaluate the efficacy of TADA therapy. Patients received the combination for one 12\u2010week cycle followed by maintenance thalidomide for an additional 3 months. Response was assessed using International Working Group criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>Among 28 enrolled patients, the median age was 66.5 years; 15 patients had MDS\/MPN\u2010unclassifiable, 8 patients had chronic myelomonocytic leukemia type 1, and 5 patients had PMF. Approximately 60% of the patients had normal cytogenetics. The <jats:italic>JAK2<\/jats:italic>V617F mutation was detected in 5 of 14 tested patients, and <jats:italic>TET2<\/jats:italic> mutations were detected in 2 of 8 tested patients. Almost half of the patients had splenomegaly. With a median on\u2010study follow\u2010up of 5.7 months, 21 patients (75%) completed the entire 12\u2010week course of therapy, and 6 patients (29%) responded to TADA. With a median extended follow\u2010up of 24.1 months for 15 evaluable patients, the median progression\u2010free survival was 14.4 months, and the median overall survival was 21.4 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>The TADA regimen yielded clinical responses in patients with PMF and MDS\/MPN. To the authors' knowledge, this study represents the first trial targeting this patient population. The results indicated that it is reasonable to incorporate multiple novel agents in the treatment of these rare diseases. 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