[logo] HealthTree Foundation
search more_vert
close
person Sign In / Create Account
arrow_back

Go back to trials list

Phase I Study Accessing the Safety of Pacritinib in Combination With Talazoparib in Patients With Myeloproliferative Neoplasms Unresponsive to Frontline JAK2 (Janus Kinase 2) Inhibition


Description

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.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. Subjects must have a diagnosis of a myeloproliferative neoplasm and progressed or become intolerant to any JAK2 directed therapy. To be eligible for the therapy, patients are required to consent to a bone marrow biopsy at the beginning of study treatment. The treatment protocol involves initiating pacritinib on day -7 (lead-in phase, starting day -7 for cycle 1) with a standard of care dose of 200mg twice daily (BID). Subsequently, talazoparib will be given on day 1 of the treatment cycle. Cohort 1 will enroll patients at the starting dose of 0.25mg talazoparib for 14 days (dose level 1) and DLT (dos

Trial Eligibility

Inclusion Criteria: * 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. * ECOG (Eastern Cooperative Oncology Group) performance status 0-2 * Subject must have received prior treatment with a single JAK2 inhibitor 4.1.6 for at least 12 weeks with documented disease progression OR subject must have appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in subjects with no evidence of splenomegaly prior to the initiation of any first line JAK2 inhibitor * Baseline QTc (corrected QT interval) \<0.47 seconds (Bazett formula) * Patients must have normal organ function as defined in protocol. * Ability to understand and willingness to sign a written informed consent and HIPAA consent document Exclusion Criteria: * 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. * Patients with history of hemorrhagic stroke and evidence of uncontrolled bleeding as well as bleeding disorder * Known HIV positive patients on combination antiretroviral therapy are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. * Pregnant or breast-feeding.

Study Info

Organization

Fox Chase Cancer Center


Primary Outcome

Maximum Tolerated Dose (MTD)


Outcome Timeframe 6 years

NCTID NCT06218628

Phases PHASE1

Primary Purpose TREATMENT

Start Date 2024-04-05

Completion Date 2029-08-22

Enrollment Target 24

Interventions

DRUG Talazoparib

DRUG pacritinib

Locations Recruiting

Fox Chase Cancer Center - Philadelphia

United States, Pennsylvania, Philadelphia


Interested in joining this trial?

Our dedicated patient navigators are here to support you by reviewing the eligibility criteria to see if you might qualify for this trial.

newsletter icon

Get the latest thought leadership on your Myelofibrosis delivered straight to your inbox

Subscribe to the weekly newsletter for news, stories, clinical trial updates, and helpful resources and events with cancer experts.

Thanks to our HealthTree Community for Myelofibrosis Sponsors:

regeneron
Karyopharm Therapeutics

Follow Us

facebook instagram youtube