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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-05

Study Completion Date

2030-08-27

Brief Summary

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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.

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Detailed Description

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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 (dose-limiting toxicity) rate will inform the subsequent dose levels (DLs).

Investigators plan to use a Bayesian Optimal Interval Design (BOIN) to determine the maximum tolerated dose (MTD) in patients with Ph-MPNs (Philadelphia chromosome negative myeloproliferative neoplasms) who have either not responded to or cannot tolerate ruxolitinib monotherapy. Subjects who are currently receiving JAK2-directed therapy will undergo a one-day washout period before starting the study treatment, as abrupt discontinuation of JAK2 inhibition can lead to side effects. This brief interval allows for the resolution of any lingering effects before initiating the new treatment. A bone marrow aspirate and or biopsy will be obtained to assess response to therapy at the end of each cycle of treatment (28 days), prior to beginning the next cycle as per physician discretion. Peripheral blood and bone marrow mononuclear cells will be checked for γ-H2AX (histone H2A family X) at set time points as a biomarker assay to assess for DNA damage in the same manner as the pre-clinical models published in our previous studies. Patients may remain on study drug unless they experience an unacceptable toxicity, fail to show a benefit, or they attain remission and it is felt by the investigator that they can proceed to an allogenic stem cell transplant.

Conditions

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Primary Myelofibrosis Post-polycythemia Vera Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Chronic Myelomonocytic Leukemia Polycythemia Vera Essential Thrombocytosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Intervention Type DRUG

pacritinib in combination with talazoparib

Interventions

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Talazoparib

pacritinib in combination with talazoparib

Intervention Type DRUG

pacritinib

pacritinib in combination with talazoparib

Intervention Type DRUG

Other Intervention Names

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talzenna vonjo

Eligibility Criteria

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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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No