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

Conditions: Myelofibrosis

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.