Polycythemia Vera (PV)Myelofibrosis (MF)Myeloproliferative Neoplasms (MPNs)Post-Polycythemia Vera MyelofibrosisPost-Essential Thrombocythemia MyelofibrosisPrimary Myelofibrosis (PMF)
Investigational drug(s) / intervention(s)
PRT12396
PRT12396: PRT12396 is an investigational oral capsule administered twice daily at the assigned dose level or RDE. Capsules are swallowed whole with water and may be taken one hour before or two hours after meals.
Study summary
This is a first-in-human, open-label, multi-center Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of PRT12396 in participants with high-risk polycythemia vera (PV) and myelofibrosis (MF), and to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE\[s\]). The study consists of a dose-escalation phase followed by a dose-expansion phase to further evaluate selected dose level(s).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures.
* Confirmed diagnosis of PV or MF according to WHO 2016 or revised ICC/WHO 2022 criteria
* Documented presence of a JAK2 V617 mutation
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Estimate life expectancy of ≥12 weeks per investigator assessment.
* Negative serum or urine pregnancy test and agree to use contraception or maintain true abstinence.
* Adequate organ function and bone marrow reserves (hematology, renal, and hepatic)
Exclusion Criteria:
* History of another malignancy within 3 years prior to enrollment, except for malignancy considered cured with low risk of recurrence.
* Clinically significant anemia due to nutritional deficiency or hemolytic disorders.
* Active or uncontrolled infection requiring systemic therapy or hospitalization.
* Any other medical or psychiatric conditions that, in the Investigator's judgment, would increase risk or interfere with study participation or interpretation of results.
* Clinically significant or uncontrolled medical conditions, including active infection or cardiovascular disease, that would increase risk or interfere with study participation.
* Unresolved toxicity Grade \>1 from prior anticancer therapy, except for alopecia or peripheral neuropathy Grade ≤2.
* Pregnancy or breastfeeding
* Known sensitivity or contraindication to any component of study, or the excipients of study treatment.
* Prior systemic therapy for PV or MF, prior or planned allogeneic hematopoietic stem-cell transplantation, recent major surgery, prior splenectomy or prior splenic irradiation, or use of hematopoietic growth factors within protocol-defined washout periods.
* Use of strong or moderate cytochrome P450 (CYP) 3A4 inhibitor or inducer, sensitive CYP3A substrates with narrow therapeutic range, or acid-reducing agents that cannot be discontinued prior to study treatment.
* Participation in another interventional clinical study.
Primary outcome measure(s)
Dose limiting toxicity (DLT) of PRT12396 — Through cycle 1 (4 weeks) Incidence of dose limiting toxicities, defined according to protocol-specified criteria
Incidence and severity of Adverse events — Through study completion, an average of 2 years Incidence and severity of treatment-emergent adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 6.0
Adverse Events Leading to Dose Modifications or Discontinuation — Through study completion, an average of 2 years Incidence of AEs leading to dose reductions, dose interruptions, treatment discontinuations, and clinically significant laboratory abnormalities
Maximum tolerated dose (MTD) and Recommended Dose(s) for Expansion (RDE[s]) of PRT12396 — Through study completion, an average of 2 years Determination of the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE\[s\]) based on evaluation of DLTs, safety, and tolerability data
Trial sites (9)
Facility
City
Region
Status
Colorado Blood Cancer Institute
Denver
Colorado
Recruiting
BRCR Global - Coral Springs
Coral Springs
Florida
Recruiting
Moffitt Cancer Center
Tampa
Florida
Recruiting
START Midwest, LLC
Grand Rapids
Michigan
Recruiting
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Trials Office
Philadelphia
Pennsylvania
Recruiting
Tennessee Oncology, PLLC - Investigational Drug Services
Nashville
Tennessee
Recruiting
Tristar BMT
Nashville
Tennessee
Recruiting
The University of Texas, MD Anderson Cancer Center
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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