A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia

Официальное название

A Phase 2 Study to Evaluate the Efficacy and Safety of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia

Обзор

The main purpose of this study is to evaluate the efficacy of selinexor in JAKi-naïve participants with myelofibrosis (MF) and with normal platelet counts or with mild to moderate thrombocytopenia based on spleen volume reduction (SVR). Additional efficacy and safety parameters will also be assessed during the study.

Вмешательства

• Препарат Selinexor 60 mg
  Participants will receive selinexor 60 mg oral tablets QW.
• Препарат Selinexor 40 mg
  Participants will receive selinexor 40 mg oral tablets QW.
• Препарат Ruxolitinib
  Participants will receive ruxolitinib per local package insert.
• Препарат Pacritinib
  Participants will receive pacritinib per local package insert. For countries where not approved, 200 mg twice daily is the starting dose.
• Препарат Momelotinib
  Participants will receive momelotinib per local package insert.

Первичные конечные точки

• Proportion of Participants with Spleen Volume Reduction ≥35% (SVR35) at Week 24 [Срок оценки: At Week 24]

Вторичные конечные точки (2)

• Absolute Mean Change in Total Symptom Score (Abs-TSS) from baseline to Week 24 [Срок оценки: At Baseline and Week 24]
• Incidence and severity of TEAEs, including TRAEs and SAEs [Срок оценки: From Baseline to EoS (approximately 48 months)]

Критерии участия

Критерии включения

• 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 or 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 C1D1 are acceptable)
• 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 greater than or equal to (>=) 50 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 transaminase (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 an average score >= 5 or total score of >= 12 at screening (at least 5 of 7 consecutive days immediately preceding C1D1) using the MFSAF V4.0
• Must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study
• Currently not eligible for stem cell transplantation
• Must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50)

Критерии исключения

• 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
• Females who are pregnant or lactating
• Prior splenectomy, splenic radiation, or a splenic embolization within 6 months prior to C1D1
• History of myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), cerebrovascular accident (transient ischemic attack \[TIA\]), ventricular arrhythmias, congestive heart failure class > 2 per New York Heart Association (NYHA) within 6 months of C1D1
• Unable to tolerate two forms of antiemetics prior to each dose for the first two cycles

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 11 центров

• Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico — Milan
• Hematology Division, Mauriziano Hospital, University of Turin — Orbassano
• Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino — Torino
• IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna
• IRCCS Ospedale Policlinico San Martino — Genova
• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST — Meldola
• Istituto Europeo di Oncologia — Milan
• Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda — Milan
• … и ещё 3 центра

Франция · 8 центров

• Institut Bergonié — Bordeaux
• Centre Hospitalier Lyon-Sud — Pierre-Bénite
• CHU Tours, Hôpital Bretonneau Service d'Hématologie thérapie cellulaire — Tours
• Chu De Nîmes - Institut De Cancérologie Du Gard — Nîmes
• Centre Hospitalier Universitaire d'Angers — Angers
• Hôpital Saint-Louis — Paris
• Hôpital Cochin — Paris
• Centre Hospitalier Universitaire de Saint-Etienne — Saint-Priest-en-Jarez

Испания · 8 центров

• Hospital Germans Trias i Pujol — Badalona
• Hospital Clínico Universitario Virgen de la Arrixaca — El Palmar
• Hospital Universitario Central de Asturias — Oviedo
• Hospital San Pedro de Alcantara — Cáceres
• Institut Català d'Oncologia Girona — Girona
• Hospital Universitario de Gran Canaria Doctor Negrin — Las Palmas de Gran Canaria
• Complejo Asistencial Universitario de Salamanca - Hospital Clínico — Salamanca
• Hospital Clínico Universitario de Valencia — Valencia

США · 7 центров

• City of Hope - Duarte Main Site — Duarte
• Maryland Oncology Hematology - Independent of SCRI/ US Oncology — Columbia
• Weill Cornell Medicine NewYork-Presbyterian — New York
• Duke University — Durham
• Cleveland Clinic — Cleveland
• MD Anderson — Houston
• Huntsman Cancer Institute — Salt Lake City

Болгария · 5 центров

• University Multiprofile Hospital for Active Treatment Sveti George - Base 1 — Plovdiv
• University Hospital Sv.Ivan Rilski - Sofia — Sofia
• University Multiprofile Hospital for Active Treatment Aleksandrovska — Sofia
• Specialized Hospital for Active Treatment of Hematological Diseases - EAD Sofia — Sofia
• University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD Depa — Stara Zagora

Греция · 5 центров

• Laiko General Hospital of Athens — Athens
• University General Hospital Attikon — Athens
• "Georgios Papanikolaou" General Hospital of Thessaloniki — Thessaloniki
• University General Hospital of Ioannina, Hematology Department — Ioannina
• University General Hospital of Larissa, Hematology Department — Larissa

South Korea · 4 центра

• Seoul St. Mary's Hospital, The Catholic University of Korea — Seocho
• Seoul National University Hospital — Seoul
• Severance Hospital — Seoul
• Pusan National University Hospital — Busan

Израиль · 3 центра

• Tel Aviv Sourasky Medical Center — Tel Aviv
• Rambam Health Care Campus — Haifa
• Carmel Medical Center — Haifa

Польша · 3 центра

• Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie — Lublin
• AIDPORT — Skórzewo
• Medicover Clinical Integrated Systems Sp. z o.o. — Torun

Румыния · 3 центра

• Coltea - Spital Clinic — Bucharest
• Spitalul Filantropia - Craiova — Craiova
• Institutul Regional de Oncologie Iasi — Iași

Тайвань · 3 центра

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City
• National Taiwan University Hospital — Taipei
• Taoyuan Chang Gung Memorial Hospital — Taoyuan

Бельгия · 2 центра

• UZ Gent — Ghent
• UZ Leuven - Campus Gasthuisberg — Leuven

Германия · 2 центра

• Marien Hospital Düsseldorf — Düsseldorf
• University Hospital Jena — Jena

Канада · 1 центр

• Research Institute of the McGill University Health Centre — Montreal

Чехия · 1 центр

• Fakultní nemocnice Olomouc — Olomouc

Дания · 1 центр

• Aarhus Universitetshospital — Aarhus N

Венгрия · 1 центр

• Semmelweis Egyetem — Budapest

Нидерланды · 1 центр

• Spaarne Gasthuis — Hoofddorp

Великобритания · 1 центр

• Guy's and Saint Thomas' NHS Foundation Trust — London

Идентификаторы

NCT: NCT05980806 · XPORT-MF-044

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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