Ensayos clínicos

Inclusion Criteria

• Age ≥ 18 years at the time of signing the ICF
• Voluntarily sign an ICF
• Pathologically confirmed PMF or post ET/PV MF as per the WHO diagnostic criteria with intermediate-1, intermediate -2, or high risk disease according to the IWG prognostic scoring system
  • Must include at least Grade 1 marrow fibrosis
  • If patients have low risk disease, then they must have symptomatic splenomegaly that is ≥ 10 cm below left costal margin by physical exam
• ECOG performance of 0-2
• Life expectancy of at least 3 months
• Recovery to Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia
• Females
  • Be of non-child bearing potential 
  • If of child-bearing potential defined as a sexually mature woman who
    • Has not undergone surgical sterilization
    • Has not been naturally post-menopausal for at least 24 consecutive months for women ≤ 55 years, or 12 consecutive months for women > 55 years
  • must have a negative serum or urine pregnancy test result within 2 weeks of first dose of study drug
• All sexually active males and females with child bearing potential must agree to use adequate methods of birth control throughout the study
  • Adequate methods of contraception include use of oral contraceptives with an additional barrier method, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, and total abstinence
• Ability to adhere to the study visit schedule and all protocol requirements

Exclusion Criteria

• Prior treatment with any inhibitor of the hedgehog pathway (e.g. GDC-0449)
• Received any treatment for myelofibrosis within 2 weeks of study entry
• Other invasive malignancies diagnosed within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer
• Inadequate hepatic function defined by
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN)
  • Direct bilirubin >1.5 x ULN
  • Cirrhotic liver disease, ongoing alcohol abuse, or known chronic active or acute hepatitis
• Inadequate renal function defined by serum creatinine >2 x ULN
• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
• Presence of active infection or systemic use of antibiotics within 72 hours of treatment
• Significant co-morbid condition or disease, which in the judgment of the Investigator, would place the patient at undue risk or interfere with the study
• Known human immunodeficiency virus (HIV) positivity
• Known hypersensitivity to IPI-926, or any of the excipients in IPI-926 capsules
• Pregnant or lactating women