Recruiting

Phase 1

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

Sponsor:

Fox Chase Cancer Center

Code:

NCT06218628

Conditions

Primary Myelofibrosis

Post-polycythemia Vera Myelofibrosis

Post-essential Thrombocythemia Myelofibrosis

Chronic Myelomonocytic Leukemia

Polycythemia Vera

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Talazoparib

pacritinib

Study Details

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.

Conditions

Primary Myelofibrosis

Post-polycythemia Vera Myelofibrosis

Post-essential Thrombocythemia Myelofibrosis

Chronic Myelomonocytic Leukemia

Polycythemia Vera

Study ID

NCT06218628

Start date

Apr 5, 2024

Status verified date

May, 2024

Completion date

Aug 27, 2030

Anticipated

Primary completion date

Aug 22, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

24 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Level -1

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)

experimental: Dose Level 1

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)

experimental: Dose Level 2

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)

experimental: Dose Level 3

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)

experimental: Dose Level 4

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)

Interventions

Talazoparib

pacritinib in combination with talazoparib

pacritinib

pacritinib in combination with talazoparib

Primary outcome measure

Maximum Tolerated Dose (MTD) [ Time Frame: 6 years ]

Central Contacts and Locations

Central contacts

Abigail Protocol Development Coordinator

215-728-2451 abigail.okeefe@fccc.edu

Locations

Fox Chase Cancer Center - Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19111-2497

Contacts

Abigail Protocol Development Coordinator

215-728-2451 abigail.okeefe@fccc.edu

More Information

Sponsor

Fox Chase Cancer Center

Last update posted

May 3, 2024

Last verified

May, 2024

Keywords

Talazoparib
Pacritinib
JAK2 Inhibition
Myeloproliferative Neoplasm

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Fox Chase Cancer Center on 2024-05-03.