This is an open label, phase II study to assess the efficacy, safety, and tolerability of Reparixin in patients with DIPSS intermediate-2, or high-risk primary myelofibrosis (PMF), post essential thrombocythemia/polycythemia vera related MF (Post ET/PV MF) after prior treatment, and those who are ineligible or refuse treatment, with a Janus kinase inhibitor (JAKi). 26 patients will be enrolled. Eligible patients will receive oral reparixin three times daily on a 4-week cycle for a core study period of 6 cycles (24 weeks). After cycle 6, patients may continue receiving reparixin once daily on a 4-week cycle if at least stable disease (SD) is met by IWG-MRT criteria until loss of response, disease progression, unacceptable toxicity, patient/physician withdrawal, or termination of study by sponsor.
Be ≥ 18 years of age at time of signing the informed consent form (ICF)
Willing to voluntarily sign the ICF
Have a pathologically confirmed diagnosis of PMF, post-ET-MF, or post-PV-MF as per the World Health Organization (WHO) diagnostic criteria with intermediate-2 or higher risk disease by DIPSS
Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer
Presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension
Documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments)
Single group
reparixin
Drugreparixin at 1200mg TID three times per day.
Efficacy of reparixin treatment per IWG/ELN criteria
To estimate the efficacy of reparixin treatment in DIPSS intermediate-2 or high-risk subjects with PMF, post PV-MF, or post ET-MF as assessed by IWG/ELN criteria. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission
Response Assessment of IWG/ELN
Response by IWG/ELN criteria at the end of Cycle 6. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission
Response Assessment of IWG/ELN
Response by IWG/ELN criteria at the end of Cycle 12. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission
Bone marrow fibrosis grade
Bone marrow fibrosis grade at the end of Cycle 6. Bone marrow fibrosis (MF) is graded as MF-0 to MF-3, with higher number indicating more disease.
Bone marrow fibrosis grade
Bone marrow fibrosis grade at the end of Cycle 12. Bone marrow fibrosis (MF) is graded as MF-0 to MF-3, with higher number indicating more disease.
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Icahn School of Medicine at Mount Sinai
Lead sponsor
Dompé Farmaceutici S.p.A
Collaborator
