Blood and Lymph Conditions

All Conditions

Neoplasms

Heart and Blood Diseases

Rare Diseases

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Chronic Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

The three main chronic myeloproliferative disorders are polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). These are clonal neoplastic diseases characterized by proliferation of one or more hematopoietic lineages. Recently a mutation of the Janus Kinase 2 (JAK2) gene that leads to the substitution of phenylalanine for valine at position 617 of the JAK2 protein, JAK2 V617F, has been found in 76% to 97% of patients with PV, 29% to 57% of patients with ET and 50% of patients with IMF. This mutation confers constitutive activity on to the JAK2 protein and appears to play an important role in the pathobiology of these conditions. However, not all patients with myeloproliferative disorders have this mutation and it may not be the primary cause of these diseases. The primary goal of this prospective natural history study is to investigate the molecular basis of these diseases in groups of patients who have JAK2 V617F and in those who do not. A second goal is to identify biomarkers for PV and the other myeloproliferative disorders that are easier to measure than JAK2 V617F. Approximately, 150 patients with myeloproliferative disorders will be studied over 3 years. The studies will involve the collection of 40 mL to 50 mL of peripheral blood from each subject. The blood will be used to assess neutrophil gene and protein expression, gene polymorphisms, and plasma protein levels.

Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders

National Institutes of Health Clinical Center (CC)

Participants with MF will receive a dose of 40 milligrams (mg) selinexor oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib twice a day (BID) based on the participants baseline platelet count.

Participants with MF will receive a dose of 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Participants with MF will receive a dose of 40 or 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Participants with MF will receive a fixed starting dose of 60 mg selinexor (RD) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Participants with MF will receive a matching placebo of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Participants will receive a dose of 40 or 60 mg selinexor oral tablets QW.

Selinexor

Participants will receive a dose of 60 mg selinexor oral tablets QW.

Participants will receive a matching placebo of selinexor oral tablets QW

Placebo

Participants will receive a dose of 15 or 20 mg ruxolitinib oral tablets BID.

Ruxolitinib

Karyopharm Medical Information

Kyle Lewler

Pankit Vachhani

Vladimir Kustanovich

Gary Schiller

Haris Ali, MD

Diane Santiago

Haris Ali

Katerina Leparskaya

Mohit Narang

Zach Moore

Erin Pettijohn

Emily Spencer

Megha Karnam

Raajit Rampal

Lynn Volk

Lindsay Rein

Basem William

Sanjay Mohan, MD

Sheila Powell

Levy Moshe

Srinivas Tantravahi

Keri Maher, DO

Georgiev Pencho

Grudeva-Popova Zhanet

Spirova Monika

Jadjiev Evgueniy

Radinoff Julian

Radinoff Atanas

Velva Nansi

Donchev Martin

Dimova Aneliya

Todorova Maria D.

Claude Vertzagias

How Johathan

Rusnakova Laura

Belohlavkova Petra

Mrakavova Barbora

Hluší Antonin

Pierre Fort Marie

Etienne Gabriel

Jeremy Bontemps

Ojeda-Uribe Mario

Vincent Gaborit

Machet Antoine

Paul Denous-Chataigner

Boyer-Perrard Francoise

Jin Huang

Kiladjian Jean-Jacques

Germo Katharina

Al-Ali Haifa Kathrin

Locke Julia

Crodel Carl

Yael Ben Ben Bassat

Koren-Michowitz Maya

Anna Turkot

Lavie David

Rula Hammond

Oshrat Hamu

Stemer Galia

Sagit Bechor

Kirgner Ilya

Frabetti Federica

Lucchesi Alessandro

Giulivo Irene

Pietrantuono Giuseppe

Deambrogi Clara

Patriarca Andrea

Silvia Marini

Cilloni Daniela

Park Jisu

Shin Hajin

Hee Ho Jun

Bang Soo-Mee

Jeon Sumi

Jung Chul Won

HyeonJi Baek

Hong Junshik

Boram Lee

Cheong June-Won

Woluntarska Dobrawa

Chraniuk Dominik

Krzanowski Jacek

Widera Julia

Grosicki Sebastian

Titieanu Amalia Andrea

Danaila Catalin Doru

Claudia Despan

Georgescu Daniela

Despan Claudia

Carlos Fernández Lamela

Abuin Blanco Altor

Isabel Merino Gonzalez

Ayala Rosa

Antonio José Martínez Mellado

Perez Lopez Raul

Magdalena Garcia Astorga

Hernandez Rivas Jesus Maria

This is a global, multicenter Phase 1/3 study to evaluate the efficacy and safety of selinexor plus ruxolitinib in JAK inhibitor (JAKi) treatment-naïve myelofibrosis (MF) participants. The study will be conducted in two phases: Phase 1 (open-label) and Phase 3 (double-blind). Phase 1 (enrollment completed) was an open-label evaluation of the safety and recommended dose (RD) of selinexor in combination with ruxolitinib and included a dose escalation using a standard 3+3 design (Phase 1a) and a dose expansion part (Phase 1b). In Phase 3, JAKi treatment-naïve MF participants are enrolled in 2:1 ratio to receive the combination therapy of selinexor + ruxolitinib or the combination of placebo + ruxolitinib.

Phase 1, open-label, selinexor dose escalation and expansion part (enrollment completed). Phase 3, randomized, double-blind, placebo-controlled part.

Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis

A Phase 1/3 Study to Evaluate Efficacy and Safety of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Ruxolitinib in Treatment-naïve Patients With Myelofibrosis

Karyopharm Therapeutics Inc

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders	NCT00433862	Polycythemia Ve... Essential Throm... Idiopathic Myel... Neutrophils Chronic Myelopr...		18 Years -	National Institutes of Health Clinical Center (CC)
Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis	NCT04562389	Myelofibrosis	Selinexor Selinexor Placebo Ruxolitinib	18 Years -	Karyopharm Therapeutics Inc
Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders	NCT00433862	Polycythemia Ve... Essential Throm... Idiopathic Myel... Neutrophils Chronic Myelopr...		18 Years -	National Institutes of Health Clinical Center (CC)
Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis	NCT04562389	Myelofibrosis	Selinexor Selinexor Placebo Ruxolitinib	18 Years -	Karyopharm Therapeutics Inc

Spots Global Cancer Trial Database for janus kinase 2