Ensayos clínicos

Inclusion Criteria:

• Men and women aged 18 years or older (20 or older in Japan).
• Diagnosis of primary myelofibrosis (PMF), post–polycythemia vera myelofibrosis (PPV-MF), or post–essential thrombocythemia myelofibrosis (PET-MF).
• DIPSS risk category of intermediate-1, intermediate-2, or high.
• Evidence of need for treatment for MF (both must be satisfied):
  • Palpable spleen of ≥ 5 cm below the left costal margin on physical examination at the screening visit;
  • Active symptoms of MF at the screening visit, as demonstrated by the presence of a total symptom score (TSS) of ≥ 10 using the Screening Symptom Form.
• Participants with an ECOG performance status score of 0, 1, or 2.
• Screening bone marrow biopsy specimen and pathology report(s) available that was obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF.
• Life expectancy of at least 24 weeks.
• Willingness to avoid pregnancy or fathering children based on the criteria below:
  • Female participants without childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible;
  • Female participants with childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participant and their understanding confirmed;
  • Male participants with childbearing potential must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 93 days after the last dose of study drug and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and their understanding confirmed.

Exclusion Criteria:

• Prior use of any Janus kinase (JAK) inhibitor.
• Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not limited to INCB040093, idelalisib, duvelisib, buparlisib, copanlisib, and umbralisib).
• Use of experimental drug therapy for MF or any other standard drug (except hydroxyurea) used for MF or another indication within 3 months of starting study drug and/or lack of recovery from all toxicities from previous therapy to ≤ Grade 1. Hydroxyurea used for MF or another indication must be discontinued 3 weeks prior to starting study drugs (Day 1).
• Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
• Recent history of inadequate bone marrow reserve; examples include but are not limited to the following:
  • Platelet count < 50 × 10^9 /L in the 4 weeks before screening or at the screening laboratory assessment; or platelet transfusion(s) within 8 weeks before screening;
  • Absolute neutrophil count < 0.5 × 10^9 /L in the 4 weeks before screening or at the screening laboratory assessment.
  • Peripheral blood blast count of > 10% at the screening hematology assessment.
  • Unwillingness to receive RBC transfusions to treat low hemoglobin levels.
• Inadequate liver and renal function at screening:
  • Total bilirubin ≥ 2.0 × ULN;
    • Note: If total bilirubin is ≥ 2.0 × ULN, the participant may enroll if the direct bilirubin is <2.0 x ULN.
  • ALT or AST > 2.5 × ULN.
• Active bacterial, fungal, parasitic, or viral infection that requires therapy.
• Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.
• Known HIV infection.
• Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion may jeopardize the safety of the participant or compliance with the Protocol.
• Active invasive malignancy over the previous 2 years.
• Splenic irradiation within 6 months before receiving the first dose of study drug.
• Concurrent use of any prohibited medications.
• Active alcohol or drug addiction that would interfere with the ability to comply with the study requirements.
• Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives(whichever is longer) before the first dose of study drug or anticipated during the study.
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
• Currently breastfeeding or pregnant.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
• History of Grade 3 or 4 irAEs from prior immunotherapy.
• Receipt of any live vaccine within 30 days of the first dose of study drug.
• Unwillingness to receive RBC transfusions to treat low hemoglobin levels
• Immediately eligible for allogeneic stem cell transplantation. 
• Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib or excipients of parsaclisib/matching placebo or ruxolitinib formulations.

Eligibility last updated 1/6/22. Questions regarding updates should be directed to the study team contact.