This is a phase 1/2 trial of pacritinib in combination with azacitidine in patients with
Chronic Myelomonocytic Leukemia (CMML). Patients will be newly diagnosed or previously
treated but could not have received a prior JAK inhibitor. Patients who have previously been
treated with a hypomethylating agent (HMA) must have received ≤ 1 cycle. Pacritinib will be
initially tested at a dose of 200mg twice daily (dose level 0) in combination with
azacitidine 75mg/m2, which can be administered subcutaneously or intravenously, for 7 days in
a 28-day cycle. If there are 2 DLTs in the first 6 patients, there will be a dose escalation
to pacritinib 100mg twice daily (dose level -1) and an additional 6 patients will be
enrolled. Based on the phase 1, 3+3 dose de-escalation design, 6-12 patients will be enrolled
in the phase 1 portion. After the completion of phase 1 and identification of the recommended
phase 2 dose (RP2D), the trial will then proceed to phase 2 which will employ a Simon two
stage design. This portion will include the 6 patients enrolled during the phase 1 portion at
the MTD. An interim analysis for futility will occur. If 3 or fewer patients have had a
clinical benefit (CB) or better, as defined by 2015 MDS/MPN IWG criteria, the PI and DSMC
will meet to discuss the totality of the evidence and determine if the trial shall proceed.
In the second stage, an additional 12 patients will be enrolled.