An Open Label Pilot Trial of the Combination of Tagraxofusp With Pacritinib in Patients With Intermediate-1 or Higher Myelofibrosis, Who Have Had Prior Therapy With the Approved JAK Inhibitors or in Which Therapy With the Approved JAK Inhibitors is Not Appropriate, Contraindicated or Declined
The goal of this open-label, single-center, pilot trial is to test the combination of Tagraxofusp (TAG) with Pacritinib (PAC) in patients with intermediate-II or higher myelofibrosis (MF), who have had prior therapy with the approved JAK1/2 inhibitor or in which therapy with the approved JAK1/2 inhibitors is not appropriate, contraindicated or declined by the subjects. The Primary Objective is to: 1\. Characterized efficacy of the combination of Tagraxofusp and Pacritinib. The Secondary Objective is to: 1\. characterize the safety profile of the combination Tagraxofusp and Pacritinib. 2, Characterize the feasibility of the combination Tagraxofusp and Pacritinib. 3. Characterize hematologic improvement with the combination Tagraxofusp and Pacritinib. 4\. Evaluate and compare the effect of Tagraxofusp and Pacritinib on participant reports of MF symptoms. Exploratory: Pharmacokinetic (PK) testing of Tagraxofusp and Pacritinib to assess clinical predictors of response. Next Generation Sequencing (NGS) Testing to define the number and the allele burden of pathological mutations, as well as the changes over the course of therapy, both in regard to progression and response. Blood will be collected and stored at KU BRCF for future study related PK analysis
• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent.
• The participant or LAR has signed informed consent prior to initiation of any study-specific procedures or treatment.
• The patient is able to adhere to the study visit schedule and other protocol requirements.
• Males and females age ≥ 18 years.
• ECOG Performance Status 0 - 2 (Appendix A).
• Life expectancy of \> 6 months.
• Patient meets the 2016 WHO diagnostic criteria for MF and has an IPSS/DIPSS/DIPSS-plus intermediate-II or higher-risk disease.
• Patients who have indications for therapy per investigator or patient's choice, such as Splenomegaly, \>5 CM BCM or mTSS ≥ 8 or mTSS Itching, night sweats, or bone pain ≥ 5 or Significant cytopenias including Hgb \<10 g/dl, Platelet count less than 75 k/UL
• Patients treated with a JAK inhibitor for \>3 months and:
• had inadequate response to treatment, i.e., \< 10% reduction of spleen by imaging, or less than 25% reduction by spleen length on physical exam or lack of control of MF symptoms that is not satisfactory to the patient. NOTE: Participants who had contraindication to therapy with the approved JAK inhibitor including subject's refusal of therapy are eligible.
⁃ A least 4 weeks have elapsed between the last dose of any MF-directed drug treatments, including hydroxyurea (HU), Interferon or glucocorticosteroids. NOTE: If patient is on a stable dose of glucocorticosteroids for another indication, they will be allowed into this study, AND patients on a stable dose of erythropoiesis-stimulating agents (ESA) are allowed on the study.
⁃ Patient is not eligible for an immediate allo-SCT.
⁃ Adequate baseline organ, cardiac, and renal function as defined by:
⁃ LVEF ≥ 50% by ECHO within 6 months of study treatment initiation No clinically significant abnormalities on a 12-lead ECG, and no QTcF ≥ 480 msec Serum creatinine ≤ 1.5 mg/dL Serum albumin ≥ 3.2 g/dL (Note: albumin infusions are not permitted to enable eligibility) INR and PTT ≤ 1.5x ULN Albumin Supplementation Prior to the first dose, participant must have serum albumin ≥ to 3.2 g/dL.
⁃ Note- for any participants with serum albumin ≤ to 4.0 g/dL, it will be advisable but up to physician's discretion to administer 25g increments of albumin infusion before the first dose.
⁃ Total bilirubin ≤ 4x ULN AST and ALT ≤ 5 x ULN ANC ≥ 0.5 x 109/L PT or INR and PTT \< = 1.5 x ULN
⁃ If the patient is a woman of child-bearing potential (WOCBP), they should have a negative serum pregnancy test no more than 7 days prior to start of treatment.
⁃ (Note: WOCBP include any female who has experienced menarche and who has not undergone successful sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level ≥ 35 mIU/mL).
⁃ Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 3 months following completion of therapy.