Purpose

The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of parsaclisib and ruxolitinib in subjects with myelofibrosis.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis
  • Palpable spleen of > 10 cm below the left subcostal margin on physical examination at the screening visit OR
  • Palpable splenomegaly of 5 to 10 cm below left subcostal margin on physical exam AND active symptoms of MF at the screening visit as demonstrated by presence of 1 symptom score ≥ 5 or 2 symptom scores ≥ 3 using the Screening Symptom Form
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria

  • Use of experimental drug therapy for myelofibrosis, or any other standard drug (eg, danazol, hydroxyurea, etc) with the exception of ruxolitinib within 6 months of starting study (combination) therapy 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
  • Unwillingness to be transfused with blood components
  • Recent history of inadequate bone marrow reserve as demonstrated by the following:
  • Platelet count < 50 × 10^9/L in the 4 weeks before screening or platelet transfusion(s) within 8 weeks before screening
  • Absolute neutrophil count levels < 0.5 × 10^9/L in the 4 weeks before screening
  • Subjects with peripheral blood blast count of > 10% at the screening or baseline hematology assessments
  • Subjects who are not willing to receive red blood cell (RBC) transfusions to treat low hemoglobin levels
  • Inadequate liver function at screening as demonstrated by the following:
  • Direct bilirubin ≥ 2.0 × the upper limit of laboratory normal (ULN). (NOTE: direct bilirubin will only be determined if total bilirubin is ≥ 2.0 × ULN)
  • alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN
  • Inadequate renal function at screening as demonstrated by creatinine clearance < 50 mL/min or glomerular filtration rate < 50 mL/min/1.73 m^2

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1: Ruxolitinib + Parsaclisib
Initial cohort dose of parsaclisib added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria.
  • Drug: Parsaclisib
    Up to 3 oral once a day (QD) doses of parsaclisib. Doses will be taken once daily for 8 weeks, followed by once weekly dosing at the same dose level.
    Other names:
    • INCB050465
  • Drug: Ruxolitinib
    The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib.
    Other names:
    • Jakafi®
Experimental
Part 2: Ruxolitinib + Parsaclisib
Part 2 will compare 2 doses of parsaclisib .
  • Drug: Parsaclisib
    Two recommended oral QD doses of parsaclisib. Once daily doses of parsaclisib will be taken for 8 weeks, followed by once weekly dosing at the same dose level.
    Other names:
    • INCB050465
  • Drug: Ruxolitinib
    The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib.
    Other names:
    • Jakafi®
Experimental
Part 3: Ruxolitinib + Parsaclisib
Part 3 will compare 2 different long term dosing strategies.
  • Drug: Ruxolitinib
    The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib.
    Other names:
    • Jakafi®
  • Drug: Parsaclisib
    20 mg oral QD dose of parsaclisib for 8 weeks. After 8 weeks patients will take either 20 mg once weekly or 5 mg once daily.
    Other names:
    • INCB050465
Experimental
Part 4: Ruxolitinib + Parsaclisib
Part 4 will compare 2 different daily dosing strategies.
  • Drug: Ruxolitinib
    The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib.
    Other names:
    • Jakafi®
  • Drug: Parsaclisib
    2 dose strategies will be compared: 5 mg parsaclisib beginning on Day 1 until end of treatment. 20 mg oral QD dose of parsaclisib for 8 weeks; after 8 weeks patients will take 5 mg once daily.
    Other names:
    • INCB050465

Recruiting Locations

Montefiore Medical Center by Agent Biomedical Research Assoc. of New York
Bronx, New York 10467
Contact:
Study Coordinator
718-920-4137

More Details

Status
Recruiting
Sponsor
Incyte Corporation

Study Contact

Incyte Corporation Call Center
1.855.463.3463

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.