Phase II Study of Reparixin in Patients With Myelofibrosis Myeloproliferative Neoplasms Research Consortium [MPN-RC 120]
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 ICF
• Able to voluntarily sign the ICF
• Have a pathologically confirmed diagnosis of PMF, post-ET-MF, or post-PV-MF as per the WHO diagnostic criteria with intermediate-2 or higher risk disease by DIPSS
• Have an ECOG performance status ≤ 2
• Willing to undergo a bone marrow biopsy at screening; however, a bone marrow biopsy obtained within 90 days of screening without intervening treatments and approved by the study chair may suffice.
• Be refractory/resistant to or intolerant of/inappropriate for JAKi therapy as defined by at least one of the following:
‣ Treatment for ≥ 3 months with inadequate efficacy as demonstrated by persistent palpable splenomegaly ≥ 5cm or symptoms related to splenomegaly.
⁃ Treatment for ≥ 28 days complicated by either:
• Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months)
∙ NCI CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of \< 20 mg BID
⁃ In the Investigator's judgment, are not candidates for available approved JAKi
• Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia
• At least two weeks must have elapsed between the last dose of any MF-directed drug treatments (including investigational therapies and excluding hydroxyurea) and study enrollment
• Have adequate organ function as demonstrated by the following:
‣ ALT (SGPT) and/or AST (SGOT) ≤ 3x ULN, or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related EMH);
⁃ Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related EMH or documented Gilbert's syndrome);
⁃ Creatinine clearance ≥ 40 mL/min ;
⁃ Platelet count ≥ 25 x 109/L;
⁃ Bone marrow and peripheral blood blast count \< 10%;
⁃ ANC ≥ 1000 mm3.
• Life expectancy of at least six months
• Women of childbearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 120 days following completion of therapy. WCBP must also have a negative serum pregnancy test at screening and Cycle 1 Day 1. Should a woman become pregnant or suspect she is pregnant while participating, she should inform her treating physician immediately.
• Ability to adhere to the study visit schedule and all protocol requirements.