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.
Simultaneously enrolled in any therapeutic clinical trial
Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study.
The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry.
The patient has received treatment with another investigational agent within 14 days of study entry.
Single group
Tagraxofusp
DrugTagraxofusp Patients will receive 12 micrograms/kg of Tagraxofusp (TAG) by IV infusion once daily for 3 consecutive days.
Pacritinib
DrugPacritinib Pacritinib (PAC) will be given orally, 200 mg twice per day starting at C2D4 and administered continuously (Subsequent cycles start on Day 1 of the Cycle).
Spleen volume reduction by MRI or CT imaging, achieving ≥ 35% reduction in spleen volume imaging from baseline to week 24.
MRI of abdomen will be performed WITHOUT contrast. If MRI is contraindicated - CT scan will be allowed (IV contrast will be used unless contraindicated). The same type of Imaging used at screening must continue to be used throughout the study.
Change from baseline in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score Version 2.0 (MPN-SAF TSS 2.0) to week 24.
Improvement in symptoms: \>/= 50% reduction in Modified Total Symptom Score (mTSS) from baseline to week 24 as measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score Version 2.0 (MPN-SAF TSS 2.0). The MPN Symptom Assessment Form) includes the assessment of symptoms that are relevant to myelofibrosis. MPN-SAF was simplified to a concise and abbreviated tool called the MPN-SAF Total Symptom Score (MPN-SAF TSS), that is used for the assessment of the 10 most relevant symptoms in subjects with MPN (fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fever) in both clinical practice and clinical trial settings. The symptom severity is rated by subjects on a scale of 1 to10 MPN-SAF-TSS: a total score will be calculated by the addition of every individual symptom score. The change from baseline will be statically measured and reported.
Number of participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0 from baseline to End of Safety Follow-up (30 days after end of treatment).
Number of participants with treatment related adverse events a assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Change from baseline in Anemia (hemoglobin GM/DL, iron ug/DL, and hematocrit %) improvement within or at 1 year
From Baseline to best response within 1 year
Patient's Global Impression (perception) of Change
Improvement in Quality of Life based on Patient Impression of Global Change (PGIC). A PGIC score of 2 for "much improved" or a score of 1 for "very much improved."
Based on the proportion of patients who report "much improved" or "very much improved" symptoms at Week 24 based on the Patient Impression of Global Change (PGIC). A PGIC score of 2 for "much improved" or a score of 1 for "very much improved." The PGIC uses a score between 1 and 7 (1 being "very much improved" to 7 being "very much worse)."
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