Clinical trial NCT05980806: A Study of Selinexor Monotherapy in Subjects with JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia
Official title: A Phase 2 Study to Evaluate the Efficacy and Safety of Selinexor Monotherapy in Subjects with JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myelofibrosis
Moderate Thrombocytopenia
Keywords: Myelofibrosis
Selinexor
Total Symptom Score
Myelofibrosis Symptom Assessment Form
Spleen Volume Reduction
TSS50
SVR35
JAK2
KPT-330
Pacritinib
Ruxolitinib
Momelotinib
Thrombocytopenia
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2023-08-08
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study with corresponding optional expansion is to evaluate the efficacy of selinexor in JAKi-naïve participants with myelofibrosis (MF) and moderate thrombocytopenia based on spleen volume reduction (SVR). Additional efficacy and safety parameters will also be assessed during the study.


Eligibility criteria: Key Inclusion Criteria:

* A diagnosis of MF or post-ET or post-PV MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report.
* Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than equal to (\>=) 450 cubic square centimeter (cm\^3) by MRI or CT scan (results from MRI or CT imaging performed within 28 days prior to screening are acceptable).
* Participants with DIPSS risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk.
* ECOG Performance Status less than or equal to (\<=) 2.
* Platelet count of 50 to less than (\<) 100 x 10\^9/L without platelet transfusion within 7 days prior to the first dose of selinexor.
* Absolute neutrophil count (ANC) \>=1.0 × 10\^9/L without need for growth factors within 7 days prior to the first dose of selinexor.
* Adequate liver function as defined by the following: aspartate transaminase (AST) and alanine aminotransferase (ALT) \<= 2.5 × upper limit normal (ULN) and serum total bilirubin \<= 3×ULN.
* Calculated creatinine clearance (CrCl) greater than (\>) 15 milliliter per minute (mL/min) based on the Cockcroft and Gault formula.
* Active symptoms of MF as determined by presence of at least 2 symptoms with a score \>= 3 or total score of \>= 10 at screening using the MFSAF V4.0.
* Participants must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study.
* Participants currently not a candidate for stem cell transplantation.
* Participants must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50).

Key Exclusion Criteria:

* More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase).
* Previous treatment with JAK inhibitors for MF.
* Previous treatment with selinexor or other XPO1 inhibitors.
* Female participants who are pregnant or lactating.
* Prior splenectomy, or splenic radiation within 6 months prior to C1D1.
* History of myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG), cerebrovascular accident (stroke or transient ischemic attack \[TIA\]), ventricular arrhythmias, congestive heart failure New York Heart Association (NYHA) class \> 2 within 6 months of C1D1.
* Participants unable to tolerate two forms of antiemetics prior to each dose for the first two cycles.

Primary outcomes:
measure: Proportion of Participants with Spleen Volume Reduction 35 (SVR35) at Week 24.
timeFrame: At Week 24
Secondary outcomes:
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs), Severity of TEAEs, Treatment Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs)
timeFrame: From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)
measure: Proportion of Participants with Total Symptom Score 50 (TSS50) at Week 24.
timeFrame: At Week 24
measure: Proportion of Participants with Anemia Response at Week 24 as per the International Working Group Myeloproliferative Neoplasms Research and Treatment and European Leukemia Network (IWG-MRT and ELN) Criteria
timeFrame: At Week 24
measure: Overall Survival (OS)
timeFrame: From date of randomization to the date of death due to any cause or EoS (assessed at approximately 48 months)
measure: Overall Response Rate (ORR) as per IWG MRT and ELN Criteria
timeFrame: From Cycle 1 Day 1 (28-day cycle) up to EoS (approximately 48 months)
measure: Proportion of Participants with SVR35 at Any Time Point.
timeFrame: From Baseline to EoS (approximately 48 months)
measure: Proportion of Participants with TSS50 at Any Time.
timeFrame: From Baseline to EoS (approximately 48 months)
measure: SVR35 Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)
timeFrame: From Baseline up to EoS (approximately 48 months)
measure: TSS50 Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)
timeFrame: From Baseline up to EoS (approximately 48 months)
measure: Anemia Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)
timeFrame: From Baseline up to EoS (approximately 48 months)
measure: SVR35 Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only
timeFrame: At Week 24
measure: TSS50 Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only
timeFrame: At Week 24
measure: Anemia Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only
timeFrame: At Week 24
measure: Number of Participants with TEAEs, Severity of TEAEs, TRAEs and SAEs in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only
timeFrame: From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)
measure: Area Under the Concentration-time Curve (AUC) of Selinexor
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
measure: Maximum Plasma Concentration (Cmax) of Selinexor
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
measure: Time at Which Cmax is Achieved (Tmax) of Selinexor
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
measure: Duration of Receptor Occupancy or Exportin 1 (XPO1) mRNA Induction
timeFrame: From Baseline up to EoS (approximately 48 months)
measure: Proportion of Participants with Post-treatment Changes in Bone Marrow
timeFrame: From Baseline up to EoS (approximately 48 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope - Duarte Main Site
state: California
city: Columbia
country: United States
facility: Maryland Oncology Hematology - Independent of SCRI/ US Oncology
state: Maryland
city: New York
country: United States
facility: Weill Cornell Medicine NewYork-Presbyterian
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti George - Base 1
city: Sofia
country: Bulgaria
facility: University Hospital Sv.Ivan Rilski - Sofia
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Aleksandrovska
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases - EAD Sofia
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD Department of Clinical Hematology
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Centre
state: Quebec
city: Tours Cedex 01
country: France
facility: CHU Tours, Hôpital Bretonneau Service d'Hématologie thérapie cellulaire
state: Indre-et-Loire
city: Nîmes
country: France
facility: Chu De Nîmes - Institut De Cancérologie Du Gard
state: Occitanie
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
state: Pays de la Loire
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
state: Rhone-Alpes
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Cochin
city: Saint-Priest-en-Jarez
country: France
facility: Centre Hospitalier Universitaire de Saint-Etienne
city: Düsseldorf
country: Germany
facility: Marien Hospital Düsseldorf
city: Jena
country: Germany
facility: University Hospital Jena
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Orbassano
country: Italy
facility: Hematology Division, Mauriziano Hospital, University of Turin
state: Torino
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milan
country: Italy
facility: Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Rome
country: Italy
facility: Università Campus Bio-Medico di Roma
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
state: Seoul Teugbyeolsi
city: Seocho-gu
country: Korea, Republic of
facility: Seoul St. Mary's Hospital, The Catholic University of Korea
state: Seoul
city: Busan-si
country: Korea, Republic of
facility: Pusan National University Hospital
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
city: Skórzewo
country: Poland
facility: AIDPORT
city: Toruń
country: Poland
facility: Medicover Clinical Integrated Systems Sp. z o.o.
city: Bucharest
country: Romania
facility: Coltea - Spital Clinic
city: Craiova
country: Romania
facility: Spitalul Filantropia - Craiova
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Girona
country: Spain
facility: Institut Català d'Oncologia Girona
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrin
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - Hospital Clínico
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
References: