Clinical Trials /

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

NCT04551053

Description:

The purpose of the study is to compare the efficacy and safety of parsaclisib when combined with ruxolitinib versus placebo combined with ruxolitinib in participants with myelofibrosis who have suboptimal response while receiving ruxolitinib monotherapy.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib
  • Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of the PI3Kδ Inhibitor Parsaclisib Plus Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib

Clinical Trial IDs

  • ORG STUDY ID: INCB 50465-304
  • NCT ID: NCT04551053

Conditions

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

Interventions

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

Purpose

The purpose of the study is to compare the efficacy and safety of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis who have suboptimal response while receiving ruxolitinib monotherapy.

Detailed Description

      Prospective participants must be on stable doses of ruxolitinib ranging from 5 mg BID to 25
      mg BID and will have been on that dose for at least the last 8 weeks prior to Day 1. At least
      3 months duration of prior ruxolitinib is required. Participants must meet Protocol-defined
      criteria for suboptimal response to ruxolitinib monotherapy. 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 a participant has completed the week 24 assessments, the participant's treatment
      assignment will then be unblinded and if found to be placebo, the participant will have the
      opportunity to crossover to begin receiving parsaclisib, together with continued ruxolitinib,
      as long as hematology parameters are adequate.
    

Trial Arms

NameTypeDescriptionInterventions
Group A : ruxolitinib +parsaclisibExperimentalParticipants will receive parsaclisib starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.
  • parsaclisib
  • ruxolitinib
Group B : ruxolitinib + placeboPlacebo ComparatorParticipants will receive placebo starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.
  • ruxolitinib
  • placebo

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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 (eg,
             danazol, hydroxyurea) 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.

          -  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 108
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 108
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:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • INCB050465
  • ruxolitinib
  • parsaclisib

Last Updated

November 27, 2020