Combining Pacritinib and Talazoparib for Patients with Myeloproliferative Neoplasms Not Responding to JAK2 Therapy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase I dose-escalation study aims to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of talazoparib when combined with standard dosing of pacritinib in patients with myeloproliferative neoplasms who have not responded to or cannot tolerate JAK2 inhibitors. Patients will undergo a lead-in phase with pacritinib before starting talazoparib, and the study will utilize a Bayesian Optimal Interval Design to assess dose-limiting toxicities. Eligibility requires a confirmed diagnosis of specific myeloproliferative neoplasms and a history of JAK2 therapy. Bone marrow biopsies will be performed to monitor treatment effects.

Why it matters

Who can join: the full rules

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.

Where it's running

• Fox Chase Cancer Center - Philadelphia
  Philadelphia, Pennsylvania, United States Recruiting

Study contacts

• Principal investigator: Peter Abdelmessieh, DO, MSc — Fox Chase Cancer Center
• Study coordinator: Abigail Protocol Development Coordinator
• Email: abigail.okeefe@fccc.edu
• Phone: 215-728-2451

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.