Combining Pacritinib and Talazoparib for Patients with Myeloproliferative Neoplasms Not Responding to JAK2 Therapy
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
This study is testing a combination of two medications, pacritinib and talazoparib, to see if they can help patients with certain blood cancers who haven't responded to other treatments.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Fox Chase Cancer Center Academic / other |
| Drugs / interventions | pacritinib, ruxolitinib |
| Locations | 1 site (Philadelphia, Pennsylvania) |
| Trial ID | NCT06218628 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates include adults over 18 with specific types of myeloproliferative neoplasms who have progressed on or are intolerant to JAK2 inhibitors.
Not a fit: Patients who have not received prior JAK2 therapy or those with low-risk myelofibrosis may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with myeloproliferative neoplasms who have limited treatment options.
How similar studies have performed: While there have been studies on JAK2 inhibitors, this specific combination of pacritinib and talazoparib is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Philadelphia, Pennsylvania
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.