This is a phase II, multicenter, open-label trial evaluating the safety and efficacy of pacritinib and selinexor in JAK inhibitor naïve patients with anemia and thrombocytopenia.
Adults ≥ 18 years of age capable of providing informed consent
Pathologically confirmed diagnosis of PMF, post-ET MF, or post-PV MF as per the World Health Organization (WHO) diagnostic criteria - Intermediate-1, Intermediate-2, or High-Risk disease by the Dynamic International Prognostic Scoring System (DIPSS)
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Baseline splenomegaly ≥ 5cm palpable below the left costal margin and in the midclavicular line OR ≥ 450cc by imaging (i.e. ultrasound, CT, MRI)
Prior treatment with Janus kinase (JAK) inhibitors
Prior treatment with selinexor or other Exportin 1 (XPO1) inhibitors
Treatment with any MF-directed therapy (including investigational therapies and excluding hydroxyurea) within 2 weeks or 5.5 half-lives, whichever is shorter, of Cycle 1 Day 1
Completed hematopoietic cell transplant (HCT)
Single group
Pacritinib
DrugPacritinib 200mg twice a day (BID) by mouth (PO)
Selinexor
DrugSelinexor 60mg once weekly (QW) by mouth (PO)
Change in spleen volume
Evaluate clinical efficacy of pacritinib and selinexor in myelofibrosis patients who are JAK inhibitor-naïve and have anemia and thrombocytopenia by assessing spleen volume reduction (SVR) of 35% or greater compared to baseline as measured by imaging (MRI/CT)
Spleen response rate
Spleen response rate (by palpation) after 6 and 12 cycles; spleen response is defined as baseline splenomegaly palpable at 5-10cm that becomes not palpable, or baseline splenomegaly of \>10cm that decreases by ≥ 50%, as measured by palpation
Change in the Myelofibrosis-Symptom Assessment Form Total Symptom Score (MF-SAF TSS)
Evaluate change in patient reported outcomes of treatment Change in MF-SAF TSS from baseline after 6 and 12 cycles; symptom response will be determined in participants with baseline MF-SAF TSS ≥ 10. The MF-SAF TSS comprises 7 items measuring MF-related symptoms. Each item is scored on a scale ranging from 0 (absent) to 10 (worst imaginable) and the items are summed for a total score. The Mf-SAF TSS is the summation of all the individual scores (0-70 scale). Symptoms response requires ≥50% reduction in the MPN-SAF TSS and will be evaluable only in patients with a baseline TSS \>= 10.
Change in Patient Global Impression of Change (PGIC)
Patient Global Impression of Change (PGIC) response after 6 and 12 cycles; PGIC response is defined as "minimally improved" or better The Patient Global Impression of Change (PGIC) will be used to assess self-reported belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Patients rate their change as "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse. Total scale from 1-7, with higher score indicating poorer health outcomes.
Anemia response
Anemia response after 6 and 12 cycles; anemia response is determined according to revised 2024 International Working Group-European LeukemiaNet (IWG-ELN) criteria and includes major response rate and minor response rate for transfusion-dependent anemia. Major response: No transfusions for 12 weeks alongside a 12-week average hemoglobin increase of 150g/L Minor response: A 50% or more reduction in transfusions and failure to meet major response thresholds.
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John Mascarenhas
Lead sponsor
Icahn School of Medicine at Mount Sinai
Sponsor institution
Sobi, Inc.
Collaborator
Karyopharm Therapeutics Inc
Collaborator
National Cancer Institute (NCI)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
