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

Phase 3

Terminated

• Conditions: Myelofibrosis; Primary Myelofibrosis; Post Essential Thrombocythemia Myelofibrosis; Post Polycythemia Vera Myelofibrosis

• Registration Number: NCT04551053
• Lead Sponsor: Incyte Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-9-11
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Terminated
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria:<br><br> - Diagnosis of PMF, PPV-MF, or PET-MF.<br><br> - DIPSS risk category of intermediate-1, intermediate-2, or high.<br><br> - Treated with ruxolitinib for = 3 months with a stable dose for at least the last 8<br> weeks prior to Day 1<br><br> - Palpable spleen of = 5 cm below the left costal margin on physical examination at<br> the screening visit.<br><br> - Active symptoms of MF at the screening visit, as demonstrated by the presence of a<br> TSS of = 10 using the Screening Symptom Form.<br><br> - Participants with an ECOG performance status score of 0, 1, or 2.<br><br> - Screening bone marrow biopsy specimen and pathology report(s) available that was<br> obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at<br> screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every<br> 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF.<br><br> - Life expectancy of at least 24 weeks.<br><br> - Willingness to avoid pregnancy or fathering children.<br><br>Exclusion Criteria:<br><br> - Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this<br> pathway include but are not limited to INCB040093, idelalisib, duvelisib,<br> buparlisib, copanlisib, and umbralisib).<br><br> - Use of experimental drug therapy for MF or any other standard drug used for MF<br> (whether for treatment of MF or another indication) with the exception of<br> ruxolitinib, within 3 months of starting study drug, and/or lack of recovery from<br> all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.<br><br> - Inability to swallow food or any condition of the upper gastrointestinal tract that<br> precludes administration of oral medications.<br><br> - Recent history of inadequate bone marrow reserve.<br><br> - Inadequate liver and renal function at screening.<br><br> - Active bacterial, fungal, parasitic, or viral infection that requires therapy.<br><br> - Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.<br><br> - Known HIV infection.<br><br> - Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion<br> may jeopardize the safety of the participant or compliance with the Protocol.<br><br> - Active invasive malignancy over the previous 2 years.<br><br> - Splenic irradiation within 6 months before receiving the first dose of study drug.<br><br> - Concurrent use of any prohibited medications.<br><br> - Active alcohol or drug addiction that would interfere with the ability to comply<br> with the study requirements.<br><br> - Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half<br> lives(whichever is longer) before the first dose of study drug or anticipated during<br> the study.<br><br> - Inadequate recovery from toxicity and/or complications from a major surgery before<br> starting therapy.<br><br> - Currently breastfeeding or pregnant.<br><br> - Any condition that would, in the investigator's judgment, interfere with full<br> participation in the study, including administration of study drug and attending<br> required study visits; pose a significant risk to the participant; or interfere with<br> interpretation of study data.<br><br> - History of Grade 3 or 4 irAEs from prior immunotherapy.<br><br> - Receipt of any live vaccine within 30 days of the first dose of study drug<br><br> - Unwillingness to receive RBC transfusions to treat low hemoglobin levels.<br><br> - Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib or<br> excipients of parsaclisib/matching placebo or ruxolitinib formulations.

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving =25% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants)

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Have a =50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v.4.0 (MFSAF v4.0) Diary;Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary;Time to the First =50% Reduction in TSS as Measured by the MFSAF v4.0 Diary;Overall Survival;Number of Participants With Any Treatment-emergent Adverse Event (TEAE);Number of Participants With Any Grade 3 or Higher TEAE;Time to the First =25% Reduction in Spleen Volume;Duration of Maintenance of a =25% Reduction in Spleen Volume