Safety Study Evaluating Twice-Daily Administration of Momelotinib in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis

This is an interventional treatment trial for Primary Myelofibrosis Read More

Inclusion Criteria:

• Diagnosis of PMF or post-ET/PV MF as per revised World Health Organization (WHO) criteria (Section 16.4, Appendix 3).
• High-risk or Intermediate-2 risk MF (as defined by the International Prognostic Scoring System [IPSS]; Section 16.6, Appendix 5); or Intermediate-1 risk MF (IPSS) associated with symptomatic splenomegaly/hepatomegaly and/or unresponsive to available therapy.
• Must be at least 18 years of age with life expectancy of ≥ 12 weeks.
• Must be able to provide informed consent and be willing to sign an informed consent form.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Section 16.3, Appendix 2).
• Must have evidence of acceptable organ function within 7 days of initiating study drug as evidenced by the following:
• AST or ALT less than or equal 2.5 x upper limit of normal (ULN) (or less than or equal to 5 x ULN if in the investigator's opinion the elevation is due to extramedullary hematopoiesis)
• Direct Bilirubin less than or equal to 2.0 x ULN
• Serum creatinine less than or equal to 2.5 x ULN
• Absolute neutrophil count ≥ 500/µL
• Platelet count ≥ 50,000/µL
• Females of childbearing potential must have a negative pregnancy test within 4 days of initiating study drug.

Exclusion Criteria:

• Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g., thalidomide), immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of study drug.
• Incomplete recovery from major surgery within four weeks of study entry.
• Radiation therapy within four weeks of study entry.
• Women of childbearing potential, unless surgically sterile for at least 3 months (i.e., hysterectomy), OR postmenopausal for at least 12 months (FSH > 30 U/mL), OR unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.
• Men who partner with a woman of childbearing potential, unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through to the end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.
• Females who are pregnant or are currently breastfeeding.
• Known positive status for HIV.
• Positive serologic testing for hepatitis B (HBsAg and HBcAb total) and hepatitis C (anti-HCV)
• Diagnosis of another malignancy unless free of disease for at least three years following therapy with curative intent. Patients with early-stage basal cell or squamous cell skin cancer, cervical intraepithelial neoplasia, cervical carcinoma in situ or superficial bladder cancer may be eligible participate at the Investigator's discretion.
• Any acute active infection.
• Cardiac dysrhythmias requiring treatment, or prolongation of the QTc (Fridericia) interval to >480 at pre-study screening, unless attributable to pre-existing bundle branch block.
• Presence of ≥ grade 2 peripheral neuropathy.
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), uncontrolled or unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism within 3 months prior to initiation of study drug.
• Uncontrolled intercurrent illness or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.