Abstract Background: The goal of therapy of immune thrombocytopenic purpura (ITP) is to produce and maintain a platelet (PLT) count greater than 30,000/μL. While anti-Rh(D) produces a rapid PLT rise (43,000/μL median overnight increase), the median duration of response is short (46 days). More than 50% of patients treated intermittently with anti-Rh(D) continue to require therapy after one year. In contrast to anti-Rh(D), the time to response and duration of response with danazol are long (median 3.1 months, 119 months, respectively). Both agents are alternatives to splenectomy. We hypothesize that danazol is an anti-Rh(D)-sparing agent and that the addition of danazol to anti-Rh(D) may decrease the requirement for anti-Rh(D) and obviate the need for continued anti-Rh(D) after one year. Methods: This is a single arm, non-randomized, phase II trial, utilizing a single stage design to compare rates of discontinuance of anti-Rh(D) at the end of one and two years. A total of 26 patients will be recruited. Treatment consists of daily danazol 600 mg in combination with anti-Rh(D) 75 μg/kg IV on day 1, to be repeated whenever PLT falls below 30,000/μL. After 1 year, danazol will be reduced to 400 mg daily for 3 months then to 200 mg daily for 9 months. Results: Seven patients have been enrolled to date (5 men/2 women). The median patient age is 43 years (range 22–51 years). The clinical course on study is summarized in Table 1. Five patients are evaluable for efficacy. Four patients have required a median of 1.5 anti-Rh(D) infusions during a median study enrollment of 43.5 weeks. Three patients have had sustained responses following the initial infusion of anti-Rh(D) noted at 14 - 35 weeks of follow-up; a second course of anti-Rh(D) was required in one of these patients at 40 weeks of follow-up. One patient has developed progressive disease. Two patients were removed from protocol therapy due to danazol toxicities; they have maintained PLT greater than 30,000/μL 6 - 35 weeks after discontinuation. No patients were noncompliant with therapy. No treatment-related deaths occurred. Conclusion: The combination of anti-Rh(D) and danazol is a novel regimen for patients with ITP. While anti-Rh(D) provides an immediate effect, danazol provides maintenance therapy. The duration of response after the initial anti-Rh(D) infusion in three patients in this study appears longer than that in patients treated with anti-Rh(D) alone, but further accrual and follow-up will be required to define toxicity and efficacy. Efficacy of anti-Rh(D) and danazol as of 07/27/06 Pt. Pt. Prior therapy Duration of danazol therapy (wks) # of anti-Rh(D) infusions administered Toxicities Comments 1 Prednisone, Anti-Rh(D)x1 47 2 Second course of anti-Rh(D) was required 40 weeks after the initial course. 2 Dexamethasone, IVIG, Anti-Rh(D)x3 14 1 Gr 1 alopecia, Gr 2 myalgias Disenrolled due to toxicity. Has maintained PLT > 30,000/ μL 6 weeks after disenrollment. 3 None 43 1 4 Dexamethasone 44 9 5 Dexamethasone, IVIG 6 4 Gr 2 anemia Disenrolled due to progressive disease (retroperitoneal bleed). 6 Prednisone 6 1 Disenrolled due to technical limitations (lack of IV access). 7 Dexamethasone 3 1 Gr 3 acne Disenrolled due to toxicity. Has maintained PLT > 30,000/ μL 35 weeks after disenrollment.