Selinexor and Pacritinib in JAK Inhibitor-naïve MF Patients With Cytopenias

Investigator-Initiated, Open-Label, Phase II Trial of Selinexor in Combination With Pacritinib in Patients With Myelofibrosis Who Are JAK Inhibitor-Naïve and Have Cytopenias (ILLUMINATE)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
• Intervention / Treatment: Drug: Pacritinib; Drug: Selinexor

Detailed Description

This Phase II, multicenter, open-label will evaluate the safety and efficacy of pacritinib and selinexor in JAK inhibitor naïve patients with anemia and thrombocytopenia. Participants will receive pacritinib monotherapy for 1 cycle (4 weeks) and will be assessed for qualification to proceed to combination therapy at Cycle 2 Day 1. Participants who qualify for combination therapy will receiving pacritinib and selinexor for the remaining cycles. Participants who do not qualify at Cycle 2 Day 1 will have weekly assessments and count checks. If they meet criteria for combination therapy at any point, selinexor will be added onto pacritinib. Participants who do not qualify for combination therapy by Cycle 4 Day 1 will complete 6 cycles of pacritinib monotherapy, complete primary endpoint assessments after 24 weeks, and discontinue study participation. Participants receiving combination therapy must demonstrate clinical benefit at Cycle 7 Day 1 (24 weeks) to continue receiving therapy until loss of response, disease progression, unacceptable toxicity, participant/physician withdrawal, or the study is terminated.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gillian Sanchez; Phone Number: (917) 581-1774; Email: gillian.sanchez@mssm.edu
• Study Contact Backup: Name: Shakira Forde; Phone Number: 212-824-8334; Email: shakira.forde@mssm.edu

Study Locations

• United States
  • Kansas
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center-Westwood
      • Principal Investigator: Abdulraheem Yacoub
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai
      • Principal Investigator: John Mascarenhas
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health Comprehensive Cancer Center
      • Principal Investigator: Ruben Mesa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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)
• Baseline anemia, defined by hemoglobin < 10 g/dL within 28 days prior to Cycle 1 Day 1
• Baseline thrombocytopenia, defined by platelet count 50-150 x 109/L without platelet transfusions within 28 days prior to Cycle 1 Day 1

• Adequate organ function as demonstrated by the following within 28 days prior to Cycle 1 Day 1:

  • ALT (SGPT) and/or AST (SGOT) ≤ 3x the upper limit of normal (ULN), or ≤ 4 x ULN if, upon judgment of the treating physician, it is believed to be due to MF-related extramedullary hematopoiesis (EMH);
  • Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN if, upon judgment of the treating physician, it is believed to be due to MF-related extramedullary hematopoiesis (EMH) or documented Gilbert's syndrome;
  • Creatinine clearance ≥ 30 mL/min;
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (Exceptions to coagulation parameters may be considered for patients who are taking concomitant anticoagulation medications or have a documented anti-phospholipid antibody, after discussion with Study Chair approval)
  • Bone marrow and/or peripheral blood blast count < 5%; and
  • Absolute neutrophil count (ANC) ≥ 1500 mm3 without need for growth factors within 7 days prior to Cycle 1 Day 1.
• Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia
• Life expectancy of at least six months
• Patients with active hepatitis B virus are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and the viral load is <100 IU/mL.
• Patients with history of hepatitis C virus (HCV) are eligible if they have received adequate curative anti-HCV treatment and HCV viral load is below the limit of quantification.
• Patients with history of human immunodeficiency virus are eligible if they have cluster of differentiation (CD)4+ T-cell counts ≥350 cells/μL, negative viral load, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year and should be on established antiretroviral therapy for at least 4 weeks.
• Women of childbearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 90 days after the last dose of study therapy
• Able to adhere to the study visit schedule and all protocol requirements

Exclusion Criteria:

• 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)
• Prior splenectomy, splenic irradiation, or splenic artery embolization within 6 months of Cycle 1 Day 1
• Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of pacritinib or selinexor, including any unresolved nausea, vomiting, or diarrhea > National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v6.0 Grade 1
• Uncontrolled or currently progressing ocular toxicities

• Moderate or severe cardiovascular disease meeting one or both of the below criteria:

  • Presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension
  • Documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments)
• Grade 2 or greater bleeding event within the past 6 months
• QT corrected by the Fridericia method (QTcF) prolongation > 480 ms or other factors that increase the risk for QT interval prolongation (eg, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or history of long QT interval syndrome)
• Recipient of organ transplant
• History of major surgery or any planned surgical procedures within 28 days prior to Cycle 1 Day 1
• Other malignancy within the last three years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated non-metastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial/non-invasive transitional cell bladder carcinoma.
• Presence of active serious infection
• Use of any prohibited medications (5.8) within two weeks or five half-lives, whichever is longer, prior to Cycle 1 Day 1
• Women who are pregnant or lactating
• Any serious, unstable medical or psychiatric condition that would prevent (as judged by the Investigator) the subject from signing the informed consent form (ICF) or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pacritinib/Selinexor; Study participants will receive pacritinib monotherapy (200mg BID orally) for the first cycle (28 days). If they qualify to add on selinexor at any point from Cycle 2 Day 1 to Cycle 4 Day 1, participants will have selinexor (60mg QW orally) added onto their pacritinib regimen.	Drug: Pacritinib; Pacritinib 200mg twice a day (BID) by mouth (PO); Other Names: VONJO; Drug: Selinexor; Selinexor 60mg once weekly (QW) by mouth (PO); Other Names: KPT-330; XPOVIO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	At 24 weeks and 48 weeks
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.	At 24 weeks and 48 weeks
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.	At 24 weeks and 48 weeks
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.	At 24 weeks and 48 weeks
Change in hemoglobin level	Hemoglobin is the protein molecule in red blood cells that carries oxygen from the lungs to the body's tissues and returns carbon dioxide from the tissues back to the lungs.	Continuously across all cycles of treatment, up to 48 weeks
Change in platelet count	Platelets are part of the blood cells. Platelets are a part of the blood clotting system and help in preventing bleeding.	Continuously across all cycles of treatment, up to 48 weeks
Progression-free survival	Progression-free survival (PFS) is defined as time from first treatment to disease progression by IWG-ELN criteria	At time of disease progression or at 48 weeks, whichever occurs first
Overall survival	Overall survival (OS) is defined as time from first treatment to death due to any cause or censored at last follow-up	At time of death or censored at last follow-up, at 48 weeks
Number of participants achieving RBC transfusion independence)	The number of participants achieving transfusion independence will be divided by the number of participants who were transfusion-dependent at baseline	at 24 weeks and at 48 weeks
Number of participants achieving platelet transfusion independence	The number of participants achieving transfusion independence will be divided by the number of participants who were transfusion-dependent at baseline	at 24 weeks and at 48 weeks

Collaborators and Investigators

• Sponsor: John Mascarenhas
• Collaborators: National Cancer Institute (NCI); Karyopharm Therapeutics Inc; Sobi, Inc.
• Investigators: Study Chair: John Mascarenhas, MD, ICAHN School of Medicine at Mount Sinai; Study Chair: Abdulraheem Yacoub, MD, University of Kansas School of Medicine; Study Chair: Ruben Mesa, MD, FACP, Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 4, 2026
• Primary Completion (Estimated): May 24, 2030
• Study Completion (Estimated): May 24, 2030

Study Registration Dates

• First Submitted: February 25, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Anemia; Myelofibrosis; Thrombocytopenia; Selinexor; Pacritinib
• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Bone Marrow Diseases; Blood Platelet Disorders; Myeloproliferative Disorders; Hemic and Lymphatic Diseases; Thrombocytopenia; Anemia; Primary Myelofibrosis; 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; selinexor
• Other Study ID Numbers: STUDY-26-00174; 5P01CA108671 (U.S. NIH Grant/Contract); MPN-RC 126 (Other Identifier: The Myeloproliferative Neoplasm Research Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The completed dataset is the sole property of the Sponsor-Investigator's institution and should not be exported to third parties, except for authorized representatives of appropriate Health/Regulatory Authorities, without permission from the Sponsor-investigator and their institution.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No