To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313)
Purpose
The purpose of the study is to compare the efficacy of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis.
Conditions
- Myelofibrosis
- Primary Myelofibrosis
- Post Essential Thrombocythemia Myelofibrosis
- Post Polycythemia Vera Myelofibrosis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Diagnosis of PMF, PPV-MF, or PET-MF. - DIPSS risk category of intermediate-1, intermediate-2, or high. - 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.
Exclusion Criteria
- Prior use of any 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 (eg, danazol, hydroxyurea) used for MF within 3 months of starting study drug and/or lack of recovery from all toxicities from previous therapy to ≤ Grade 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. - Inadequate liver and renal function at screening. - 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
- Masking Description
- Triple blind
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Group A : parsaclisib + ruxolitinib |
Participants will receive parsaclisib and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count. |
|
|
Placebo Comparator Group B : placebo + ruxolitinib |
Participants will receive placebo and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count. |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Incyte Corporation
Study Contact
Detailed Description
This is a Phase 3, randomized, double-blind study of the combination of the PI3Kδ inhibitor parsaclisib or matching placebo and the JAK1/2 inhibitor ruxolitinib in participants with PMF or secondary MF (PPV-MF or PET-MF) with DIPSS risk category of intermediate or high. Prospective participants must have not received prior MF therapy with a JAK inhibitor or a PI3K inhibitor. After participants have been determined to be eligible for the study and completed the baseline symptom diary assessment for 7 days, they will be randomized to 1 of 2 treatment groups, with stratification for platelet count (≥ 100 × 10^9/L vs 50 to < 100 × 10^9/L inclusive) and DIPSS risk category (high vs intermediate-2 vs intermediate-1). Once all enrolled participants completed the week 24 assessments the study will be unblinded and and participants randomized to placebo will have the opportunity to cross over to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.