This phase I trial tests the safety, side effects and best dose of talazoparib in combination with pacritinib in treating patients with myeloproliferative neoplasms that did not respond to frontline JAK2 inhibitors. Talazoparib is a PARP inhibitor. PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA). Blocking PARP may prevent cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Pacritinib is in a class of medications called JAK2 inhibitors. Some specific gene changes in blood cells can send faulty signals to the bone marrow, the spongy tissue inside the bones, and lead to myeloproliferative neoplasms. Pacritinib can interrupt these signals that may be causing the myeloproliferative neoplasms. Giving talazoparib together with pacritinib may be safe, tolerable, and/or effective in treating patients with myeloproliferative neoplasms that did not respond to frontline JAK2 inhibitors.
Additional locations may be listed on ClinicalTrials.gov for NCT06218628.
Locations matching your search criteria
United States
Pennsylvania
Philadelphia
Fox Chase Cancer CenterStatus: Active
Contact: Peter Abdelmessieh
Phone: 215-214-3119
Temple Health Jeanes HospitalStatus: Active
Contact: Peter Abdelmessieh
Phone: 215-214-3119
PRIMARY OBJECTIVE:
I. 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).
SECONDARY OBJECTIVE:
I. To define the safety of talazoparib in combination with pacritinib including the rate of grade 3 or higher adverse events.
EXPLORATORY OBJECTIVES:
I. To estimate the efficacy in terms of response rate (RR), overall survival (OS), progression free survival (PFS) and disease control rate (DCR).
II. To evaluate the optimal dose of talazoparib for maximum gamma-H2AX expression in malignant myeloproliferative cells.
III. To measure the efficacy of this combination therapy on mutational allelic burden.
OUTLINE: This is a dose-escalation study of talazoparib in combination with pacritinib.
Patients receive pacritinib orally (PO) twice daily (BID) on days -7-28 of cycle 1 and on days 1-28 of subsequent cycles and receive talazoparib PO once daily (QD) on days 1-7 or 1-14 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment if the treating physician determines the patient may continue benefitting from the combination. Additionally, patients may undergo bone marrow aspiration and/or biopsy on study and during follow-up, and undergo collection of blood samples and ultrasound on study.
Upon completion of study treatment, patients are followed up every 3 months for 2 years.
Lead OrganizationFox Chase Cancer Center
Principal InvestigatorPeter Abdelmessieh
