To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)

Korábbi kezelés

• 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 used for MF (whether for treatment of MF or another indication) with the exception of ruxolitinib, within 3 months of starting study drug, and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.
• 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.
• 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

Más betegség

• 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.
• 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.
• 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.
• Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib or excipients of parsaclisib/matching placebo or ruxolitinib formulations.

Laborértékek

• Unwillingness to receive RBC transfusions to treat low hemoglobin levels.

Egyéb

• Inadequate liver and renal function at screening.
• Currently breastfeeding or pregnant.

• Diagnosis of PMF, PPV-MF, or PET-MF.
• DIPSS risk category of intermediate-1, intermediate-2, or high.
• Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8 weeks prior to Day 1
• 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 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.