Clinical trial NCT02436135: 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
Official title: A Phase 1b Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Idelalisib in Subjects Receiving Ruxolitinib as Therapy for Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis With Progressive or Relapsed Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Myelofibrosis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-05-06
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 28 days
measure: Percentage of Participants Experiencing Adverse Events Related to Idelalisib Within 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 28 days
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Within 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
timeFrame: First dose date up to 28 days
measure: Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Within 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 28 days
Secondary outcomes:
measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events Beyond 28 Days of Idelalisib Exposure
timeFrame: First dose date up to the last dose date (maximum:15.1 months) plus 30 days
measure: Percentage of Participants Experiencing Adverse Events Related to Idelalisib Beyond 28 Days of Idelalisib Exposure
timeFrame: First dose date up to the last dose date (maximum:15.1 months) plus 30 days
measure: Percentage of Participants Experiencing Abnormal Laboratory Abnormalities Beyond 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
timeFrame: First dose date up to the last dose date (maximum:15.1 months) plus 30 days
measure: Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Beyond 28 Days of Exposure
timeFrame: First dose date up to the last dose date (maximum:15.1 months) plus 30 days
measure: Rate of Overall Response
timeFrame: Start of treatment to end of treatment ( up to 15.1 months)
measure: Plasma Concentration of Idelalisib and GS-563117 (Idelalisib Metabolite)
timeFrame: Predose Week 2, 1.5 hour Week 2, and Predose Week 3
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: