Table 1.

Recommendations for appropriateness of patient populations and primary end points in clinical trials in Ph-neg MPNs according to the therapy key questions

Key question: Developing new drug therapies in MPNs  Phase I trials should enroll patients with high-risk prognostic categories. Dose-limiting toxicity, maximum tolerated dose, pharmacokinetic and pharmacodynamic profile are the most appropriate primary end points  Phase II trials in PV or ET should enroll patients in need of therapy for the disease. Phase II trials in MF should enroll patients in need of therapy for contrasting the major disease manifestations, excluding rare or life-threatening complications. Overall response rate and duration of response are the most appropriate primary end points  Phase III trials should enroll patients in need of therapy for the disease. Overall survival or progression-free survival are the most appropriate primary end points Key question: Preventing disease progression in MF patients with early disease  Trials should enroll previously untreated patients with IPSS score 0 (low-risk disease). Progression-free survival or event-free survival are the most appropriate primary end points Key question: Testing new drugs for the relief of MF-associated symptoms  Trials aimed at evaluating drugs efficacy on splenomegaly should enroll patients in need of therapy for splenomegaly. The efficacy end point should be response on splenomegaly according to the IWG-MRT/ELN criteria  Trials aimed at evaluating the drugs efficacy on anemia should enroll patients in need of therapy for anemia. The efficacy end point should be response on anemia according to the IWG-MRT/ELN criteria Key question: Preventing vascular events in PV and ET  Trials aimed at preventing vascular events in PV and ET should enroll patients with high risk of thrombosis. The efficacy end point should be time to vascular event

Abbrevations: ELN, European LeukemiaNet; ET, essential thrombocythemia; IPSS, International Prognostic Scoring System; IWG-MRT, International Working Group for MPN Research and Treatment; MF, myelofibrosis; MPN, myeloproliferative neoplasm; PV, polycythemia vera.