Clinical Trials /

To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis

NCT04551066

Description:

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.

Related Conditions:
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis
  • Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Combination of PI3Kδ Inhibitor Parsaclisib and Ruxolitinib in Participants With Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: INCB 50465-313
  • NCT ID: NCT04551066

Conditions

  • Myelofibrosis
  • Primary Myelofibrosis
  • Post Essential Thrombocythemia Myelofibrosis
  • Post Polycythemia Vera Myelofibrosis

Interventions

DrugSynonymsArms
parsaclisibINCB050465Group A : parsaclisib + ruxolitinib
ruxolitinibJakafi, JakaviGroup A : parsaclisib + ruxolitinib
placeboGroup B : placebo + ruxolitinib

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Group A : parsaclisib + ruxolitinibExperimentalParticipants will receive parsaclisib and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.
  • parsaclisib
  • ruxolitinib
Group B : placebo + ruxolitinibPlacebo ComparatorParticipants will receive placebo and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.
  • ruxolitinib
  • placebo

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of participants achieving targeted reduction in spleen volume
Time Frame:Baseline to Week 24
Safety Issue:
Description:Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).

Secondary Outcome Measures

Measure:Proportion of participants who have a targeted reduction in Total Symptom Score (TSS)
Time Frame:Baseline to Week 24
Safety Issue:
Description:Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
Measure:Change in TSS
Time Frame:Baseline to Week 24
Safety Issue:
Description:Change in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
Measure:Time to the first ≥ 50% reduction in TSS
Time Frame:Baseline to Week 24
Safety Issue:
Description:Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 36 months
Safety Issue:
Description:OS is defined as randomization date to death due to any cause.
Measure:Number of Treatment Emergent Adverse Events (TEAE)
Time Frame:Up to approximately 36 months
Safety Issue:
Description:Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 35 days after last dose of study drug.
Measure:Time of onset of targeted reduction in spleen volume
Time Frame:Baseline to Week 144
Safety Issue:
Description:Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).
Measure:Duration of maintenance of targeted reduction in spleen volume
Time Frame:Baseline to Week 144
Safety Issue:
Description:Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • INCB050465
  • ruxolitinib
  • parsaclisib

Last Updated

January 22, 2021