Pacritinib w/ Talazoparib in Pts w/ Myeloproliferative Neoplasms Unresponsive to JAK2 Inhibition

Phase 1

Recruiting

• Conditions: Primary Myelofibrosis; Chronic Myelomonocytic Leukemia; Polycythemia Vera; Essential Thrombocytosis; Post-essential Thrombocythemia Myelofibrosis; Post-polycythemia Vera Myelofibrosis
• Interventions: Drug: Talazoparib; Drug: pacritinib

• Registration Number: NCT06218628
• Lead Sponsor: Fox Chase Cancer Center

Brief Summary

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.

Detailed 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. 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, p...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-01-12
• Study First Submitted QC: 2024-01-12
• Study First Posted: 2024-01-23
• Study Start: 2024-04-05
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-02
• Last Update Posted: 2024-05-03
• Primary Completion: 2029-08-22
• Study Completion: 2030-08-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Level -1	Talazoparib	0.25 mg (PO, QD) Talazoparib (Days 1-7) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level 1	Talazoparib	0.25 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level 1	pacritinib	0.25 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level 3	Talazoparib	0.75 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level 3	pacritinib	0.75 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level 4	Talazoparib	1 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level 4	pacritinib	1 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level -1	pacritinib	0.25 mg (PO, QD) Talazoparib (Days 1-7) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level 2	Talazoparib	0.5 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)
Dose Level 2	pacritinib	0.5 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD)	6 years	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 Outcome Measures

Name	Time	Method
Rate of grade 3 or higher toxicity	6 years	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	6 years	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	6 years	Disease control rate, defined by improvement in quality of life measures, spleen size, and hematological recovery
Progression free survival	6 years	Progression free survival, defined as the time of enrollment to disease progression
Overall survival	6 years	Overall survival, defined by time from enrollment to death from any cause

Trial Locations

Locations (1)

Fox Chase Cancer Center - Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States