Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Idelalisib in Adults Receiving Ruxolitinib as Therapy for Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis With Progressive or Relapsed Disease
Condition: Myelofibrosis
MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: Idelalisib; Ruxolitinib
Intervention description: Idelalisib tablets administered orally for 24 weeks; Ruxolitinib will be administered per standard of care according to package insert
Intervention MeSH terms: Idelalisib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the safety, tolerability, and
      pharmacokinetics of idelalisib in adults receiving ruxolitinib as therapy for intermediate to
      high-risk primary myelofibrosis (PMF), post-polycythemia vera, or post-essential
      thrombocythemia myelofibrosis (post-PV MF or post-ET MF) with progressive or relapsed
      disease.

      This is a dose-escalation study. There will be 4 cohorts (A, B, C, D). Participants will
      receive an escalating dose or dose frequency of idelalisib based on the safety data of
      available cohort(s).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Individuals must have been on a stable dose of ruxolitinib for at least 4 weeks prior
             to study entry

          -  Individuals with PMF, post-PV MF, or post-ET MF classified as high risk or
             intermediate risk as defined by the Dynamic International Prognostic Scoring System
             (DIPSS) for PMF or DIPSS Plus, if cytogenetics are available

          -  Individuals with PMF, post-PV MF, or post-ET MF who are receiving ruxolitinib and meet
             2013 Revised International Working Group for Myelofibrosis Research and Treatment
             (IWG-MRT) and European Leukemia Net (ELN) response criteria with progressive and
             relapsed disease, with modifications for progressive disease complete remission (CR),
             partial remission (PR), or clinical improvement (CI)

          -  European Cooperative Oncology Group (ECOG) performance status of ≤ 2

          -  Required screening laboratory values as described in the protocol

          -  Willing and able to comply with scheduled visits, drug administration plan, imaging
             studies, laboratory tests, other study procedures, and study restrictions including
             mandatory prophylaxis for pneumocystis jiroveci pneumonia (PJP)

          -  Able to understand and willing to sign the informed consent form

        Key Exclusion Criteria:

          -  Individuals on a stable ruxolitinib dose of 5 mg once daily

          -  History of prior allogeneic bone marrow progenitor cell or solid organ transplantation

          -  Ongoing drug-induced liver injury, alcoholic liver disease, non-alcoholic
             steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by
             cholelithiasis, cirrhosis of the liver

          -  Ongoing drug-induced pneumonitis

          -  Ongoing inflammatory bowel disease

          -  Ongoing alcohol or drug addiction

          -  Symptomatic congestive heart failure (New York Heart Association Classification >
             Class II), unstable angina, or unstable cardiac arrhythmia requiring medication

          -  Known hypersensitivity to the study investigational medicinal product (IMP), the
             metabolites, or formulation excipients

          -  Unwilling or unable to take oral medication

          -  Unresolved non-hematologic toxicities from prior therapies that are > Common
             terminology Criteria for Adverse Events (CTCAE) Grade 1 (with the exception of
             alopecia [Grade 1 or 2 permitted])

          -  Pregnant or lactating females

          -  Cytomegalovirus (CMV): Ongoing infection, treatment, or prophylaxis within the past 28
             days

        NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.