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

NCT07447817 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: STUDY-26-001745P01CA108671MPN-RC 126
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis

Keywords

Myelofibrosis; Anemia; Thrombocytopenia; Pacritinib; Selinexor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Spleen response rate

  At 24 weeks and 48 weeks

• Change in the Myelofibrosis-Symptom Assessment Form Total Symptom Score (MF-SAF TSS)

  At 24 weeks and 48 weeks

• Change in Patient Global Impression of Change (PGIC)

  At 24 weeks and 48 weeks

• Anemia response

  At 24 weeks and 48 weeks

• Change in hemoglobin level

  Continuously across all cycles of treatment, up to 48 weeks

Study Arms (1)

Pacritinib/Selinexor

EXPERIMENTAL

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; Drug: Selinexor

Interventions

Pacritinib DRUG

Pacritinib 200mg twice a day (BID) by mouth (PO)

Also known as: VONJO

Pacritinib/Selinexor

Selinexor DRUG

Selinexor 60mg once weekly (QW) by mouth (PO)

Also known as: KPT-330; XPOVIO

Pacritinib/Selinexor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• John Mascarenhas: lead
• Sobi, Inc.: collaborator
• Karyopharm Therapeutics Inc: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (3)

The University of Kansas Cancer Center-Westwood

Westwood, Kansas, 66205, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Wake Forest Baptist Health Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis; Anemia; Thrombocytopenia

Interventions

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

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Platelet Disorders; Cytopenia

Study Officials

• 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 CHAIR

Central Study Contacts

Gillian Sanchez

CONTACT

(917) 581-1774; gillian.sanchez@mssm.edu

Shakira Forde

CONTACT

212-824-8334; shakira.forde@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 4, 2026
• Study Start: May 4, 2026
• Primary Completion (Estimated): May 24, 2030
• Study Completion (Estimated): May 24, 2030
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)