Methods
toxicity, bone pain, pruritus, sweats
REMISSION
Ruxo-BEAT (NCT02577926) is a multicenter, open-label, two-arm phase 2b trial with a target population of 380 pts, divided into two strata of 190 untreated PV (a maximum of previous 6 weeks of HU, anagrelide, or interferon therapy was allowed) and 190 untreated or pretreated ET pts. All patients provided written informed consent, and the study was approved by the central ethics committee at RWTH Aachen University Hospital (EK 345/14) and at the local ethics committee of each center. The most relevant inclusion criteria were an age of 18 years of age or older, ECOG performance status of ≤ 2, a diagnosis of either PV or ET according to the WHO 2008 classification. Moreover, PV pts and ET pts had to be classified as high risk according to defined criteria as outlined below: for patients with high-risk PV or PV with indication for cytoreductive therapy due to progressive myeloproliferation, any one of the following had to be fulfilled ([Pts in each stratum were randomized in a 1:1 ratio to receive either RUX or best available therapy (BAT). Crossover from BAT to RUX was allowed in eligible patients after 6 months who did not achieve complete remission but still had sufficient hematologic reserves (platelet count ≥ 140 × 10The current futility analysis of PV patients randomized to RUX, after 50 PV patients overall had been enrolled, was pre-specified in the trial protocol in order to exclude early failure or excessive toxicity. Of these 50 patients, 28 patients were randomized into the RUX arm. Closure of the PV subgroup was pre-specified if no favorable trend were observed for any of the following variables: (1) improvement (decrease) in the hematocrit level during 6 months of treatment or (2) improvement of one of the following three symptom variables assessed by physician’s judgement or via MPN-SAF during 6 months of treatment: pruritus, night sweats, or bone pain. Furthermore, the change in JAK2V617F allele burden during the first 6 months of treatment was analyzed as part of the scientific research program. Differences between screening (Hct) or baseline (all other variables) and end of month 6 (EOM6) (all variables) were calculated using McNemar’s test (for physician-assessed pruritus and night sweats) or the Wilcoxon signed rank test (all other variables). Probability values of < 0.05 were considered significant.