This is a prospective phase I dose-escalation study, with the primary objective to access the MTD and find the RP2D of talazoparib, given in combination with standard of care dosing of pacritinib.
Patients must have histologically or cytologically confirmed primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF), post-essential thrombocythemia-myelofibrosis (PET-MF), chronic myelomonocytic leukemia, polycythemia vera, or essential thrombocytosis according to the 2008 World Health Organization criteria
Subject has at least 2 symptoms with a score ≥ 3 or a total score of ≥ 12, as measured by the MFSAF(Myelofibrosis Symptom Assessment Form) v4.0
Subject classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+70).
Age > 18 years.
Patients may not be receiving any other investigational agents
Subjects must not be experiencing toxicity due to prior therapy that has not resolved to ≤Grade 1 by study registration, with the exception of sensory neuropathy related to previous systemic therapy exposure, alopecia and fatigue.
Patients that have transformed to Acute Myeloid Leukemia defined by >20% blasts count on peripheral blood smear or bone marrow biopsy evaluation
Uncontrolled inter-current illness including, but not limited to, any other malignancy (with the exception of hormonal therapy for breast cancer/prostate cancer in remission >1 year and for non-hormonal therapies for other cancers in remission for >3 years), other ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Sequential
Talazoparib
Drugpacritinib in combination with talazoparib
pacritinib
Drugpacritinib in combination with talazoparib
Maximum Tolerated Dose (MTD)
To define the maximum tolerated dose (MTD) of talazoparib in combination with standard of care dosing of pacritinib in order to establish a recommended phase II dose (RP2D).
Rate of grade 3 or higher toxicity
Rate of grade 3 or higher toxicities occurring with the combination of talazoparib and pacritinib in patients with MPNs that have failed to respond to one line of JAK2 directed therapy.
Response rate
Response rate defined by a 35% or greater spleen volume reduction (SVR) or a \>25% reduction in total symptom score (TSS) at week 24 (per IWG-MTR (International Working Group for Myelofibrosis Research and Treatment) criteria).
Disease control rate
Disease control rate, defined by improvement in quality of life measures, spleen size, and hematological recovery
Progression free survival
Progression free survival, defined as the time of enrollment to disease progression
Click on the lead sponsor to view all of their trials.
