Interim Analysis on a Dutch HOVON Multicenter Randomized Open Label Phase II Trial on 3 Rituximab Dosing Schemes In Chronic ITP Patients:

Abstract

Abstract 2514The overall short term effectivity of Rituximab in the treatment of ITP is reported to be around 50%. In most studies the traditional CD20 dosing scheme of 4 weekly interspaced 375 mg/m2 doses is used although other single-arm studies suggest comparable effectivity of lower doses. To investigate alternative dosing schemes, we conducted an open label phase II multicenter trial and randomized 156 ITP patients that were refractory for corticosteroid treatment, between three schemes. Questions were: are higher CD20 peak levels of value and is dose saving a feasible approach in early responding patients? The treatment arms were: A) 375 mg/m2 once a week for 4 weeks, B) 750 mg/m2 once a week for 2 weeks and C) 375 mg/m2 once a week for 2 weeks, in early and sustained responding patients (= within 15 days and still responding at 43 days) and another 2 × 375 mg/m2 to patients not fulfilling these criteria. In retrospect, seven of the 156 patients appeared ineligible at randomization and were therefore excluded from all analyses. Here we report on the best response within 71 days as primary end point for the first 105 patients that were included, i.e. 35 per treatment armArm A (n=35) 4 × 375 mg/m2 Arm B (n=35) 2 × 750 mg/m2 Arm C (n=35) 2 or 4 × 375 mg/m2 Patient characteristics Male/female, % 37/63 49/51 43/57 WHO 0/1/2/not reported, % 86/6/–/9. 77/20/3/– 91/9/–/– Age in years, median (range) 56 (19–77) 56 (17–82) 41 (18–80) On stable corticosteroid, % 36 29 46 Splenectomized, % – 15 11 Baseline plt count × 109/l, median (range) 16 (3–31) 15 (1–30) 19 (2–30) Treatment outcome, % Early responses in Arm C 26 All best responses within 71d 46 42 51 CR: >150 × 109 plt/l 20 14 14 GR: >50 × 109 plt/l 20 14 23 MR: >30 × 109 plt/l AND >2 × baseline 6 14 14 No response 54 58 49 Treatment failure at 6 months, % (standard error) 57 (8) 60 (8) 54 (9)So far, on the basis of the within 71 days overall response data, no superior dosing scheme of CD20 can yet be discerned.