What Is Pacritinib?
Pacritinib is an investigational oral kinase inhibitor currently being studied in clinical trials. It works by blocking specific proteins such as JAK2 (including the mutant JAK2V617F), FLT3, IRAK1, and ACVR1. By inhibiting JAK2, pacritinib aims to interfere with cell growth and survival pathways. This drug is being investigated for the treatment of various blood cancers and related conditions, primarily myelofibrosis, a rare bone marrow disorder. It is also being explored for other conditions like acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), and Graft-versus-Host Disease (GVHD).
Clinical trials for pacritinib began on June 15, 2012, with the latest trial projected to conclude on March 4, 2026. A total of 49 trials have been conducted or are ongoing, enrolling 2,851 participants. Of these, 17 trials are currently recruiting new participants, and 12 trials have been completed.
Uses and Conditions Under Study
Pacritinib is being investigated across a range of conditions, with a primary focus on myelofibrosis and other hematologic (blood) disorders.
- Myelofibrosis: This group includes Primary Myelofibrosis, Myelofibrosis, Post-polycythemia Vera Myelofibrosis, and Post-essential Thrombocythemia Myelofibrosis. Myelofibrosis is a rare bone marrow cancer where scar tissue builds up, impairing the bone marrow's ability to produce blood cells. Pacritinib, as a JAK2 inhibitor, is being studied to address the underlying mechanisms of this disease. These conditions are being explored in a combined total of 23 trials.
- Other Blood Cancers and Disorders: Pacritinib is also under investigation for other serious blood conditions. This includes Chronic Myelomonocytic Leukemia (4 trials), Myelodysplastic Syndromes (3 trials), and Myeloproliferative Neoplasm (3 trials). Additionally, trials are exploring its potential in Acute Myeloid Leukemia (AML), Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), and Waldenström macroglobulinemia (WM). In these conditions, pacritinib's ability to inhibit specific kinases is being evaluated for its therapeutic effects.
- Inflammatory and Autoimmune Conditions: The drug is being studied for VEXAS syndrome (2 trials), a rare inflammatory disorder, and Graft-versus-Host Disease (GVHD). GVHD is a serious complication that can occur after a stem cell transplant, where donor immune cells attack the recipient's tissues. Pacritinib's immune-modulating properties are being assessed in these contexts.
- Other Cancers: Pacritinib is also being investigated in 2 trials for Prostate Cancer.
- Pharmacokinetic Studies: Pacritinib has been studied in 2 trials involving healthy subjects to understand how the body processes the drug.
Dosing
Pacritinib is administered orally, typically as a tablet. The most commonly studied dose in adult trials is 200 mg twice a day (BID), resulting in a total daily dose of 400 mg. Some studies have also investigated a total daily dose of 200 mg, given as 100 mg twice daily, or even 100 mg once daily (QD).
Patients usually take pacritinib by mouth, with doses spaced approximately 12 hours apart (e.g., once in the morning and once in the evening). Treatment is often continuous, administered in 28-day cycles without a break between cycles. The duration of treatment can vary, continuing until disease progression, unacceptable side effects occur, or the patient no longer benefits from the therapy.
Doses may be adjusted based on individual patient needs and tolerance. For example, the dose may be reduced to 100 mg BID (200 mg total daily dose) or 100 mg once daily (QD) to manage adverse events. While most detailed dosing information pertains to adult studies, pacritinib has also been investigated in pediatric populations, though specific pediatric dosing regimens are not detailed here.
Side Effects
In a clinical trial involving 96 patients treated with Pacritinib, the most common side effect was bradycardia (a slower-than-normal heart rate). 15.6% of patients taking Pacritinib experienced bradycardia, compared to 10.9% on placebo.
Other common side effects observed in patients taking Pacritinib, along with their rates compared to placebo, include:
- Increased alanine aminotransferase (a liver enzyme): 15.6% of patients on Pacritinib compared to 16.8% on placebo.
- Diarrhea: 12.5% of patients on Pacritinib compared to 4.0% on placebo.
- Hypokalemia (low potassium levels): 12.5% of patients on Pacritinib compared to 11.9% on placebo.
- Anemia (low red blood cell count): 12.5% of patients on Pacritinib compared to 17.8% on placebo.
- Acute kidney injury: 9.4% of patients on Pacritinib compared to 6.9% on placebo.
- Increased aspartate aminotransferase (another liver enzyme): 9.4% of patients on Pacritinib compared to 5.9% on placebo.
- Anxiety: 6.3% of patients on Pacritinib compared to 3.0% on
Currently Recruiting Trials
Pacritinib is currently being investigated in a variety of clinical trials for patients with different blood disorders and cancers. These studies aim to understand how safe and effective pacritinib is, sometimes alone and sometimes in combination with other treatments. One trial, NCT06675123, is a Phase 1 study enrolling up to 10 patients with relapsed or refractory mantle cell lymphoma. This trial, sponsored by City of Hope Medical Center, tests pacritinib in combination with a BTK inhibitor. The National Cancer Institute is sponsoring a Phase 1/Phase 2 study, NCT06303193, for adults and pediatric participants 12 years or older with myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms, with an enrollment target of 160 individuals. For patients with myelofibrosis who have thrombocytopenia, the Grupo Español de Enfermedades Mieloproliferativas Crónicas PH Negativas is conducting a Phase 2 trial, NCT07394153, planning to enroll 30 participants. Another Phase 2 study from the University of Washington, NCT07148947, is exploring pacritinib with standard azacitidine or decitabine as a bridge to stem cell transplant for patients with accelerated and blast phase myeloproliferative neoplasms, aiming for 27 patients. Theradex is sponsoring NCT07033598, a Phase 2 trial comparing pacritinib to hydroxyurea in 66 adults with advanced proliferative chronic myelomonocytic leukemia. A Phase 2 study, NCT06986174, is evaluating pacritinib's safety and efficacy in 30 patients with relapsed or refractory Waldenström macroglobulinemia. Several trials are exploring pacritinib in combination therapies or for rare conditions. The University of Kansas Medical Center's NCT06414681, an Early Phase 1 study, combines tagraxofusp with pacritinib for 20 patients with myelofibrosis who have previously received or cannot take approved JAK inhibitors. Swedish Orphan Biovitrum is sponsoring NCT06782373, a Phase 2 study assessing pacritinib's effectiveness and safety in 78 patients with VEXAS syndrome. Other studies include NCT06052618, a Phase 2 trial by the National Cancer Institute for 75 patients with Kaposi Sarcoma Herpesvirus-associated Multicentric Castleman Disease and KSHV-associated Inflammatory Cytokine Syndrome. Washington University School of Medicine is conducting NCT06538181, a Phase 1 study of pacritinib in 15 patients with VEXAS syndrome. For advanced lung adenocarcinoma, The University of Texas Health Science Center at San Antonio is running NCT06516887, a Phase 1/Phase 2 study of bemcentinib plus pacritinib, targeting 44 participants. Douglas Tremblay's NCT06159491 is a Phase 1/Phase 2 trial of pacritinib combined with azacitidine in 26 patients with chronic myelomonocytic leukemia. Fox Chase Cancer Center is leading NCT06218628, a Phase 1 study of pacritinib with talazoparib in 24 patients with myeloproliferative neoplasms unresponsive to JAK2 inhibition. The University of Michigan Rogel Cancer Center's NCT04858256 is a Phase 2 study of pacritinib in 100 patients with relapsed/refractory T-cell lymphoproliferative neoplasms. Finally, the National Cancer Institute is sponsoring NCT05531786, a Phase 1/Phase 2 study of pacritinib in 50 patients with refractory chronic graft-versus-host disease after stem cell transplantation. The University of Washington's NCT04282187 is a Phase 2 study of decitabine with ruxolitinib, fedratinib, or pacritinib for 25 patients with accelerated/blast phase myeloproliferative neoplasms.Where to Participate
Clinical trials for pacritinib are currently recruiting across the United States, with studies active at 34 sites in 22 cities across 17 states. This broad reach helps ensure that patients in various regions have access to potential new treatments. The cities with the most active recruiting sites include:- Bethesda, Maryland (3 sites)
- Duarte, California (3 sites)
- Houston, Texas (3 sites)
- Seattle, Washington (3 sites)
- New York, New York (3 sites)
- Boston, Massachusetts (2 sites)
- Rochester, Minnesota (2 sites)
- Tampa, Florida (2 sites)
- Durham, North Carolina (2 sites)
- Cleveland, Ohio (2 sites)
Development Timeline
The journey of pacritinib in clinical development began on June 15, 2012, with its first clinical trial. Since then, a robust program has unfolded, encompassing a total of 49 trials and enrolling 2,851 participants. The latest trial is projected to conclude on March 4, 2026, indicating ongoing research and commitment to understanding pacritinib's full potential. Initial investigations for pacritinib explored conditions such as IBS-C and hyperphosphatemia. Over time, the development pipeline significantly expanded, focusing on a range of hematologic disorders. Key areas of expansion included myeloproliferative neoplasms like Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, and Chronic Myelomonocytic Leukemia, as well as Myelodysplastic Syndromes and Myelofibrosis. More recently, studies have also broadened to include conditions like VEXAS syndrome, Waldenström Macroglobulinemia, and various lymphoproliferative disorders. The majority of pacritinib's clinical studies have progressed through early and mid-stage development, with 21 trials reaching Phase 2, 16 in Phase 1, and 8 as Phase 1/Phase 2 studies. There have also been 3 Phase 3 trials and 1 Early Phase 1 study. CTI BioPharma has been a significant driver of this research, sponsoring 13 trials, alongside contributions from institutions like Washington University School of Medicine, University of Michigan Rogel Cancer Center, and the National Cancer Institute. This progression through phases reflects a continuous effort to evaluate pacritinib's safety and efficacy across a growing spectrum of medical needs.