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

NCT06414681 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00160238
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Myelofibrosis，MF

Keywords

Myelofibrosis; MF; JAK 1/2; Tagraxofusp; TAG; Pacritinib; PAC; Tagraxofusp with Pacritinib; Intermediate II Myelofibrosis; Higher Myelofibrosis

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline to up to 24 weeks

• 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.

  Baseline to up to 24 weeks

Secondary Outcomes (7)

• 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).

  Baseline to End of Safety follow up to End of Treatment (up to 1 year)

• Change from baseline in Anemia (hemoglobin GM/DL, iron ug/DL, and hematocrit %) improvement within or at 1 year

  Baseline, Week 24 and End of Treatment (up to 1 year)

• Patient's Global Impression (perception) of Change

  Every cycle (each cycle is 28 days) day 1 starting at Cycle 2 to End of Treatment (up to 1 year)

• 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."

  Baseline to up to 24 weeks

• Change from baseline in platelet count in K/UL within 1 year

  Baseline, up to 24 weeks and End of Treatment (up to 1 year)

Study Arms (1)

Tagrxofusp (IV) in combination with Pacritinib (Oral)

EXPERIMENTAL

Tagraxofusp Patients will receive 12 micrograms/kg of Tagraxofusp (TAG) by IV infusion once daily for 3 consecutive days. Pacritinib 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).

Drug: Tagraxofusp; Drug: Pacritinib

Interventions

Tagraxofusp DRUG

Tagraxofusp Patients will receive 12 micrograms/kg of Tagraxofusp (TAG) by IV infusion once daily for 3 consecutive days.

Tagrxofusp (IV) in combination with Pacritinib (Oral)

Pacritinib DRUG

Pacritinib 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).

Tagrxofusp (IV) in combination with Pacritinib (Oral)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation.
• Any condition or other contraindication to therapy as deemed by the principal investigator to place the subject at an unacceptably high risk for toxicities.
• Is pregnant or breastfeeding.
• Has a known allergic reaction to any excipient contained in the study drug formulation.
• Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment.
• Prior therapy with Tagraxofusp or Pacritinib.
• Presence of peripheral blood or bone marrow blast count \> 10%
• Active Graft versus Host Disease (GVHD)
• For patients who have previously had Stem Cell Therapy (SCT) - The patient is receiving immunosuppressive therapy.
• EXCEPTION: low-dose prednisone (≤10 mg/day) - for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days prior to study treatment and there must be no evidence of Grade ≥ 2 GVHD.

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

The University of Kansas Cancer Center

Fairway, Kansas, 66204, United States

RECRUITING

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Related Links

• U.S Food and Drug Administration - News and Events for Human Drugs. FDA approves drug for adults with rare form of bone marrow disorder
• Pacritinib Granted Accelerated Approval for Use in Myelofibrosis With Severe Thrombocytopenia
• U.S. Food \& Drug Administration. For Healthcare Professionals \| FDA's Examples of Drugs that Interact with CYP Enzymes and Transporter Systems

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

tagraxofusp; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Abdulraheem Yacoub, Doctor of Medicine

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

KUCC Navigation

CONTACT

913-588-3671; kucc_navigation@kumc.edu

Victoria Guinn, B.S

CONTACT

913-574-1446; vguinn@kumc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: May 16, 2024
• Study Start: August 25, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)