Myeloproliferative Neoplasms Clinical Trial

Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis

Summary

This is a global, Phase 1/2, multicenter, open-label study to evaluate the safety and efficacy of selinexor plus ruxolitinib in treatment naïve myelofibrosis (MF) participants. The study will be conducted in two phases: Phase 1a/1b and Phase 2. The Phase 1a of the study will be dose escalation (non-randomized dose finding study) to determine the maximum tolerated dose [MTD], recommended Phase 2 dose (RP2D), and evaluate safety and preliminary efficacy and will follow a standard 3+3 design. The Phase 1b of the study will be dose expansion (non-randomized efficacy exploration) at the determined RP2D to further assess the safety and preliminary efficacy at this dose level. The Phase 2 (randomized efficacy exploration) of the study will include MF participants who are treatment naïve randomized 1:1 to receive the combination therapy of selinexor and ruxolitinib versus (vs) ruxolitinib monotherapy.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

A diagnosis of primary MF or post-essential thrombocythemia (ET) or postpolycythemia- vera (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 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 international prognostic scoring system (DIPSS) risk category of intermediate-1, or intermediate-2, or high-risk.
Participants >=18 years of age.
Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (<=) 2.
Platelet count >= 100*10^9/liter (L) without platelet transfusion.
Absolute neutrophil count (ANC) >=1.0 *10^9/L without need for growth factors within 7 days prior to C1D1.
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 <= 2 × ULN.
Calculated creatinine clearance (CrCl) greater than (>) 15 milliliters per minute (mL/min) based on the Cockcroft and Gault formula.
Participants with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for > 8 weeks and the viral load is less than (<) 100 international units/milliliter (IU/mL).
Participants 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.
Participants with history of human immunodeficiency virus (HIV) are eligible if they have CD4+ T-cell counts >= 350 cells/microliter (cells/mcL), 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 (ART) for at least 4 weeks.
Female participants of childbearing potential must have a negative serum pregnancy test at screening and within 3 days prior to first dose on C1D1 and agree to use highly effective methods of contraception throughout the selinexor treatment period and for 90 days following the last dose of selinexor treatment. A woman is considered of childbearing potential, i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
Male participants who are sexually active must use highly effective methods of contraception throughout the study treatment period and for 90 days following the last dose of selinexor treatment. Male participants must agree not to donate sperm during the study treatment period and for at least 90 days after the last dose of selinexor treatment.
Participants must sign written informed consent in accordance with federal, local, and institutional guidelines.
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 Myelofibrosis Symptom Assessment Form (MFSAF) V4.0.
Participant currently not eligible for stem cell transplantation.
Participants must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study.
Life expectancy of greater than 6 months in the opinion of the investigator.
Participants with no other concomitant malignancies or history of another malignancy within 2 years prior to C1D1 except for adequately treated early-stage basal cell or squamous cell carcinoma of skin, adequately treated carcinoma in situ of breast or cervix or organ confined prostate cancer, or PV or ET.

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.
Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (e.g., vomiting or diarrhea > CTCAE v 5.0 Grade 1).
Received strong cytochrome P450 3A (CYP3A) inhibitors <= 7 days prior to selinexor dosing OR strong CYP3A inducers <= 14 days prior to selinexor dosing (Phase 1 participants only)
Major surgery < 28 days prior to C1D1.
Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to C1D1; however, prophylactic use of these agents is acceptable (including parenteral).
Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participants safety, prevent the participant from giving informed consent, or being compliant with the study procedures, or confound the ability to interpret study results.
Female participants who are pregnant or lactating.
Prior splenectomy, or splenic radiation within 6 months prior to C1D1.
Unable or unwilling to undergo CT scan or MRI per protocol.
Participants with contraindications or known hypersensitivity to selinexor or ruxolitinib or excipients.
History of pulmonary hypertension.
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 at least 2 cycles.

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 3

Estimated Enrollment:

330

Study ID:

NCT04562389

Recruitment Status:

Recruiting

Sponsor:

Karyopharm Therapeutics Inc

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 58 Locations for this study

See Locations Near You

UAB Division of Hematology/Oncology
Birmingham Alabama, 35294, United States More Info
Kyle Lewler
Contact
[email protected]
Pankit Vachhani
Principal Investigator
UCLA - Satellite Site
Beverly Hills California, 90210, United States More Info
Vladimir Kustanovich
Contact
310-206-5756
[email protected]
Gary Schiller
Principal Investigator
City of Hope
Duarte California, 91010, United States More Info
Haris Ali, MD
Contact
626-356-4673
[email protected]
Haris Ali, MD
Principal Investigator
UCLA - Satellite Site
Encino California, 93003, United States More Info
Vladimir Kustanovich
Contact
310-206-5756
[email protected]
Gary Schiller
Principal Investigator
City of Hope - Irvine Lennar - Satellite
Irvine California, 92618, United States More Info
Diane Santiago
Contact
949-671-4115
[email protected]
Haris Ali
Principal Investigator
UCLA
Los Angeles California, 90095, United States More Info
Vladimir Kustanovich
Contact
310-206-5756
[email protected]
Gary Schiller
Principal Investigator
The Oncology Institute of Hope & Innovation
Pasadena California, 91105, United States
Maryland Oncology Hematology-Satellite
Annapolis Maryland, 21401, United States More Info
Katerina Leparskaya
Contact
240-223-1391
[email protected]
Mohit Narang
Principal Investigator
Maryland Oncology Hematology-Satellite
Brandywine Maryland, 21004, United States More Info
Katerina Leparskaya
Contact
240-223-1391
[email protected]
Mohit Narang
Principal Investigator
Maryland Oncology Hematology
Columbia Maryland, 21044, United States More Info
Katerina Leparskaya
Contact
240-223-1391
[email protected]
Mohit Narang
Principal Investigator
Maryland Oncology Hematology-Satellite
Rockville Maryland, 20850, United States More Info
Katerina Leparskaya
Contact
240-223-1391
[email protected]
Mohit Narang
Principal Investigator
Maryland Oncology Hematology-Satellite
Silver Spring Maryland, 20904, United States More Info
Katerina Leparskaya
Contact
240-223-1391
[email protected]
Mohit Narang
Principal Investigator
The Cancer & Hematology Centers -Satellite Site
Grand Rapids Michigan, 49546, United States More Info
Zach Moore
Contact
616-389-1675
[email protected]
Erin Pettijohn
Principal Investigator
The Cancer & Hematology Centers of Muskegon
Norton Shores Michigan, 49444, United States More Info
Emily Spencer
Contact
616-954-5550
[email protected]
Erin Pettijohn
Principal Investigator
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States More Info
Megha Karnam
Contact
310-206-5756
[email protected]
Raajit Rampal
Principal Investigator
Duke Cancer Institue
Durham North Carolina, 27705, United States More Info
Lynn Volk
Contact
919-684-9889
[email protected]
Lindsay Rein
Principal Investigator
OhioHealth
Columbus Ohio, 43214, United States More Info
Basem William
Contact
[email protected]
Basem William
Principal Investigator
Vanderbilt Ingram Cancer Center
Nashville Tennessee, 37232, United States More Info
Sanjay Mohan, MD
Contact
615-936-8422
[email protected]
Sanjay Mohan, MD
Principal Investigator
Texas Oncology
Dallas Texas, 75246, United States More Info
Sheila Powell
Contact
214-370-1000
[email protected]
Levy Moshe
Principal Investigator
Huntsman Cancer Institute
Salt Lake City Utah, 84112, United States More Info
Srinivas Tantravahi
Contact
801-213-6170
[email protected]
Srinivas Tantravahi
Principal Investigator
VCU Massey Cancer Center
Richmond Virginia, 23298, United States More Info
Keri Maher, DO
Contact
760-954-3800
[email protected]
Keri Maher, DO
Principal Investigator
University Multiprofile Hospital for Active Treatment Sveti George - Base 1
Plovdiv , 4002, Bulgaria More Info
Georgiev Pencho
Contact
+359 32 602 298
[email protected]
Grudeva-Popova Zhanet
Principal Investigator
University Multiprofile Hospital for Active Treatment Aleksandrovska
Sofia , 1431, Bulgaria More Info
Spirova Monika
Contact
+359882067375
[email protected]
Jadjiev Evgueniy
Principal Investigator
University Multiprofile Hospital for Active Treatment St. Ivan Rilski
Sofia , 1431, Bulgaria More Info
Radinoff Julian
Contact
+359 882 508 919
[email protected]
Radinoff Atanas
Principal Investigator
Specialized Hospital for Active Treatment of Hematological Diseases - EAD Sofia
Sofia , 1797, Bulgaria More Info
Donchev Martin
Principal Investigator
University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich
Stara Zagora , 6003, Bulgaria More Info
Dimova Aneliya
Contact
+359882730043
[email protected]
Todorova Maria D.
Principal Investigator
Research Institute of the McGill University Health Centre
Montreal Quebec, H4A 3, Canada More Info
Claude Vertzagias
Contact
(514) 934-1934
[email protected]
How Johathan
Principal Investigator
Fakultní Nemocnice Hradec Králové
Hradec Králové , 500 0, Czechia More Info
Rusnakova Laura
Contact
+420495834237
[email protected]
Belohlavkova Petra
Principal Investigator
Fakultní Nemocnice Olomouc
Olomouc , 779 0, Czechia More Info
Mrakavova Barbora
Contact
+420 588445433
[email protected]
Hluší Antonin
Principal Investigator
Institut Bergonié
Bordeaux Aquitaine, 33000, France More Info
Pierre Fort Marie
Contact
+33 5 56 33 04 48
[email protected]
Etienne Gabriel
Principal Investigator
Hôpital Emile Muller
Mulhouse Grand Est, 68100, France More Info
Jeremy Bontemps
Contact
+33389647728
[email protected]
Ojeda-Uribe Mario
Principal Investigator
Hôpital Bretonneau
Tours Cedex Indre-et-Loire, 37044, France More Info
Vincent Gaborit
Contact
+33 218370540
[email protected]
Machet Antoine
Principal Investigator
Centre Hospitalier Universitaire d'Angers
Angers Pays De La Loire, 49 93, France More Info
Paul Denous-Chataigner
Contact
+33 6 65 80 74 89
[email protected]
Boyer-Perrard Francoise
Principal Investigator
Hôpital Saint-Louis
Paris , 75010, France More Info
Jin Huang
Contact
+33142499397
[email protected]
Kiladjian Jean-Jacques
Principal Investigator
Universitätsklinikum Halle
Halle Sachsen-Anhalt, 6120, Germany More Info
Germo Katharina
Contact
[email protected]
Al-Ali Haifa Kathrin
Principal Investigator
Universitätsklinikum Jena
Jena Thuringen, 7747, Germany More Info
Crodel Carl
Principal Investigator
Shamir Medical Center (Assaf Harofeh)
Be'er Ya'akov Central District, 70300, Israel More Info
Yael Ben Ben Bassat
Contact
+972 52-8922935
[email protected]
Koren-Michowitz Maya
Principal Investigator
Hadassah University Hospital - Mount Scopus - Satellite Site
Jerusalem Jerusalem District, 91120, Israel More Info
Lavie David
Principal Investigator
Hadassah University Hospital Ein Kerem
Jerusalem Jerusalem District, 91120, Israel More Info
Rula Hammond
Contact
+972-5-23246716
[email protected]
Lavie David
Principal Investigator
Western Galilee Hospital-Nahariya
Nahariya Northern District, 22100, Israel More Info
Oshrat Hamu
Contact
+9725 4 9107175
[email protected]
Stemer Galia
Principal Investigator
Tel Aviv Sourasky Medical Center
Tel Aviv , 64239, Israel More Info
Sagit Bechor
Contact
+972-3-6947802
[email protected]
Kirgner Ilya
Principal Investigator
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
Meldola Forli-Cesena, 47014, Italy More Info
Frabetti Federica
Contact
+39 0543739292
[email protected]
Lucchesi Alessandro
Principal Investigator
IRCCS Centro di Riferimento Oncologico di Basilicata
Rionero In Vulture Potenza, 85028, Italy More Info
Giulivo Irene
Contact
[email protected]
Pietrantuono Giuseppe
Principal Investigator
Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
Novara , 28100, Italy More Info
Deambrogi Clara
Contact
+39 0321 3732094
[email protected]
Patriarca Andrea
Principal Investigator
Azienda Ospedaliera Ordine Mauriziano di Torino
Torino , 10128, Italy More Info
Silvia Marini
Contact
+39 011 5082224
[email protected]
Cilloni Daniela
Principal Investigator
Pusan National University Hospital
Busan Gwang'yeogsi [Pusan-Kwangyokshi] , 49241, Korea, Republic of More Info
Shin Hajin
Principal Investigator
Seoul National University Bundang Hospital
Seongnam-si Gyeonggido [Kyonggi-do] , 13605, Korea, Republic of More Info
Bang Soo-Mee
Principal Investigator
Samsung Medical Center
Seoul Teugbyeolsi [Seoul-T'ukpyolshi] , 6351, Korea, Republic of More Info
Jung Chul Won
Principal Investigator
Seoul National University Hospital
Seoul , 03080, Korea, Republic of More Info
HyeonJi Baek
Contact
+82-2-2072-4990
[email protected]
Hong Junshik
Principal Investigator
Severance Hospital
Seoul , 03722, Korea, Republic of More Info
Cheong June-Won
Principal Investigator
Medicover Integrated Clinical Services (MICS) - Centrum Medyczne Toruń
Toruń Kujawsko-Pomorskie, 87-10, Poland More Info
Woluntarska Dobrawa
Contact
+48 56 300 43 80
[email protected]
Chraniuk Dominik
Principal Investigator
Szpital Specjalistyczny w Brzozowie - Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
Brzozów Podkarpackie, 36-20, Poland More Info
Krzanowski Jacek
Principal Investigator
Pratia Onkologia Katowice
Katowice Slaskie, 40-51, Poland More Info
Widera Julia
Contact
+48 571 313 538
[email protected]
Grosicki Sebastian
Principal Investigator
Institutul Regional De Oncologie Iasi
Moldova Iasi, 70048, Romania More Info
Titieanu Amalia Andrea
Contact
[email protected]
Danaila Catalin Doru
Principal Investigator
Coltea - Spital Clinic
Bucuresti , 02012, Romania More Info
Claudia Despan
Contact
+40 724 960 564
[email protected]
Georgescu Daniela
Principal Investigator
Spitalul Clinic Colentina
Bucuresti , 20125, Romania More Info
Despan Claudia
Contact
+40 724 960 564
[email protected]
Georgescu Daniela
Principal Investigator
Hospital Universitario Lucus Augusti
Lugo , 27003, Spain More Info
Carlos Fernández Lamela
Contact
+34 982 296121
[email protected]
Abuin Blanco Altor
Principal Investigator
Hospital Universitario 12 de Octubre
Madrid , 28041, Spain More Info
Isabel Merino Gonzalez
Contact
+34 913908652
[email protected]
Ayala Rosa
Principal Investigator
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia , 30120, Spain More Info
Antonio José Martínez Mellado
Contact
+34 968 369 382
[email protected]
Perez Lopez Raul
Principal Investigator
Complejo Asistencial Universitario de Salamanca - Hospital Clínico
Salamanca , 37007, Spain More Info
Magdalena Garcia Astorga
Contact
+34 923291100
[email protected]
Hernandez Rivas Jesus Maria
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 3

Estimated Enrollment:

330

Study ID:

NCT04562389

Recruitment Status:

Recruiting

Sponsor:


Karyopharm Therapeutics Inc

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.