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

Overview

About this study

The purpose of this study is to compare the effectiveness of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Men and women aged 18 years or older (20 or older in Japan).
  • Diagnosis of primary myelofibrosis (PMF), post–polycythemia vera myelofibrosis (PPV-MF), or post–essential thrombocythemia myelofibrosis (PET-MF).
  • DIPSS risk category of intermediate-1, intermediate-2, or high.
  • Evidence of need for treatment for MF (both must be satisfied):
    • 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 total symptom score (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 based on the criteria below:
    • Female participants without childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible;
    • Female participants with childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participant and their understanding confirmed;
    • Male participants with childbearing potential must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 93 days after the last dose of study drug and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and their understanding confirmed.

Exclusion Criteria:

  • Prior use of any Janus kinase (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 (except hydroxyurea) used for MF or another indication within 3 months of starting study drug and/or lack of recovery from all toxicities from previous therapy to ≤ Grade 1. Hydroxyurea used for MF or another indication must be discontinued 3 weeks prior to starting study drugs (Day 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; examples include but are not limited to the following:
    • Platelet count < 50 × 10^9 /L in the 4 weeks before screening or at the screening laboratory assessment; or platelet transfusion(s) within 8 weeks before screening;
    • Absolute neutrophil count < 0.5 × 10^9 /L in the 4 weeks before screening or at the screening laboratory assessment.
    • Peripheral blood blast count of > 10% at the screening hematology assessment.
    • Unwillingness to receive RBC transfusions to treat low hemoglobin levels.
  • Inadequate liver and renal function at screening:
    • Total bilirubin ≥ 2.0 × ULN;
      • Note: If total bilirubin is ≥ 2.0 × ULN, the participant may enroll if the direct bilirubin is <2.0 x ULN.
    • ALT or AST > 2.5 × ULN.
  • 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.
  • Unwillingness to receive RBC transfusions to treat low hemoglobin levels
  • Immediately eligible for allogeneic stem cell transplantation. 
  • Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib or excipients of parsaclisib/matching placebo or ruxolitinib formulations.

Eligibility last updated 1/6/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jeanne Palmer, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
.
CLS-20519534

Mayo Clinic Footer