Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
POIESIS
A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib vs Placebo Plus Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
1 other identifier
interventional
600
18 countries
204
Brief Summary
This clinical trial is evaluating whether addition of navtemadlin to ruxolitinib treatment will provide more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have a suboptimal response to ruxolitinib treatment alone. Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2024
Longer than P75 for phase_3
204 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 3, 2024
CompletedFirst Submitted
Initial submission to the registry
June 21, 2024
CompletedFirst Posted
Study publicly available on registry
June 28, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
September 25, 2025
October 1, 2024
2.6 years
June 21, 2024
September 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To compare spleen volume reduction (SVR35) between Arm 1 and Arm 2
The proportion of subjects in each arm with SVR35 by MRI/CT scan (central review) 24 weeks after start of the randomized period
24 weeks
To compare total symptom score reduction (TSS50) between Arm 1 and Arm 2
The proportion of subjects in each arm with a TSS50 by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 24 weeks after start of the randomized period
24 weeks
Secondary Outcomes (2)
To compare time to progression between Arm 1 and Arm 2
Up to 8 years
To compare overall survival (OS) between Arm 1 and Arm 2
Up to 8 years
Study Arms (2)
Arm 1
EXPERIMENTALNavtemadlin administered orally once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles. Ruxolitinib administered orally twice a day.
Arm 2
ACTIVE COMPARATORNavtemadlin placebo administered orally once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles. Ruxolitinib administered orally twice a day.
Interventions
Eligibility Criteria
You may qualify if:
- Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
- High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- JAK-inhibitor treatment naive
You may not qualify if:
- Prior Splenectomy
- Splenic irradiation within 3 months prior to the first dose
- Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
- Eligible for Bone Marrow Transplant
- Peripheral blood or bone marrow blast count ≥ 10 percent
- PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
- ECOG performance status of 0 to 2
- Treatment with a stable dose of ruxolitinib
- Suboptimal response to run-in ruxolitinib treatment
- Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 × 10\^9/L
- Peripheral blood or bone marrow blast count ≥ 10 percent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (215)
UAB Hospital
Birmingham, Alabama, 35233, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
Mayo Clinic - Phoenix
Phoenix, Arizona, 85054, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92037, United States
UCLA Hematology/Oncology Clinic - Los Angeles
Los Angeles, California, 90095, United States
Scripps Health, Prebys Cancer Center
San Diego, California, 92103, United States
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502, United States
Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado, 80012, United States
Medical Oncology Hematology Consultants, PA
Newark, Delaware, 19713, United States
MedStar Georgetown University Hospital, Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224, United States
University of Miami
Miami, Florida, 33136, United States
AdventHealth Cancer Institute
Orlando, Florida, 32803, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Mission Cancer + Blood
Des Moines, Iowa, 50314, United States
University of Kansas Cancer Center - Westwood
Westwood, Kansas, 66205, United States
Norton Cancer Institute
Louisville, Kentucky, 40207, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231, United States
The Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Hospital
Ann Arbor, Michigan, 48109, United States
Henry Ford Cancer Institute - Brigitte Harris Cancer Pavilion
Detroit, Michigan, 48202, United States
Nebraska Hematology - Oncology, P.C.
Lincoln, Nebraska, 68506, United States
Mohtaseb Cancer Center and Blood Disorders
Henderson, Nevada, 86442, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Brookdale University Hospital and Medical Center
Brooklyn, New York, 11212, United States
Cayuga Cancer Center
Ithaca, New York, 14850, United States
Northwell Health, R.J. Zuckerberg Cancer Center
Lake Success, New York, 11042, United States
ICAHN School of Medicine at Mount Sinai
New York, New York, 10029-6574, United States
Montefiore Einstein Comprehensive Cancer Center
The Bronx, New York, 10467, United States
Medical University of South Carolina (MUSC)
Charleston, North Carolina, 29425-8900, United States
Atrium Health Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Regional Medical Oncology Center
Wilson, North Carolina, 27893, United States
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157, United States
Gabrail Cancer Center
Canton, Ohio, 44718, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219, United States
Cleveland Clinic Cancer Center at Fairview Hospital
Cleveland, Ohio, 44111, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Independence Family Health Center - Cleveland Clinic
Independence, Ohio, 44131, United States
Hillcrest Hospital - Cleveland Clinic
Mayfield Heights, Ohio, 44124, United States
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, 97401, United States
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
West Penn Hospital
Pittsburgh, Pennsylvania, 15224, United States
Tennessee Oncology
Chattanooga, Tennessee, 37404, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
UT - SouthWestern
Dallas, Texas, 75390, United States
U.T. MD Anderson Cancer Center
Houston, Texas, 77030, United States
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Virginia Cancer Institute
Richmond, Virginia, 23229, United States
VCU Medical Center
Richmond, Virginia, 23298, United States
Virginia Oncology Associates - Virginia Beach
Virginia Beach, Virginia, 23456, United States
Fred Hutchinson Cancer Centre
Seattle, Washington, 98109, United States
Northwest Medical Specialties, PLLC - Tacoma
Tacoma, Washington, 98405, United States
Sheboygan Cancer & Blood Specialists
Sheboygan, Wisconsin, 53081, United States
Royal Hobart Hospital (RHH)
Hobart, Tasmania, 7000, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
Royal Adelaide Hospital
Adelaide, SA 5000, Australia
Monash Medical Center Clayton
Clayton, VIC 3168, Australia
Townsville University Hospital
Douglas, QLD 4814, Australia
Gosford Hospital
Gosford, NSW 2250, Australia
St George Hospital
Kogarah, NSW 2217, Australia
The Royal Melbourne Hospital - Peter MacCallum Cancer Center
Melbourne, VIC 3000, Australia
The Alfred Hospital
Melbourne, VIC 3004, Australia
Royal Perth Hospital
Perth, 6000, Australia
Calvary Mater Newcastle Hospital
Waratah, NSW 2298, Australia
University Hospital Graz, Department of Internal Medicine
Graz, 8036, Austria
Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology)
Innsbruck, 6020, Austria
Regional Hospital Hochsteiermark - Leoben, Department of Internal Medicine, Department of Hematology and Oncology
Leoben, 8700, Austria
Ordensklinikum Linz GmbH Elisabethinen Hospital, Department of Internal Medicine I - Hemato-Oncology
Linz, 4020, Austria
Kepler University Hospital GmbH, Med Campus 3, University Clinic for Hematology and Internal Oncology
Linz, 4021, Austria
Medical University Vienna
Vienna, 1090, Austria
Hospital Ottakring, Department of Internal Medicine I
Vienna, 1160, Austria
Antwerp Hospital Network (ZNA) Cadix
Antwerp, 2030, Belgium
University Hospitals Leuven, Campus Gasthuisberg
Leuven, 3000, Belgium
University Hospital Center Sart-Tilman
Liège, 4000, Belgium
General Hospital Delta
Roeselare, 8800, Belgium
UCL Mont-Godinne University Hospitals
Yvoir, 5530, Belgium
Clinical Hospital Centre Rijeka
Rijeka, 51 000, Croatia
University Hospital of Split
Split, 21000, Croatia
General Hospital of Sibenik-Knin County
Šibenik, 22000, Croatia
Clinical Hospital Dubrava
Zagreb, 10000, Croatia
Clinical Hospital Merkur
Zagreb, 10000, Croatia
Solmed Clinic
Zagreb, 10000, Croatia
University Hospital Centre Zagreb
Zagreb, 10000, Croatia
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
Brno, 625 00, Czechia
University Hospital Hradec Kralove
Hradec Králové, 500 05, Czechia
University Hospital Ostrava
Ostrava, 708 52, Czechia
University Hospital Kralovske Vinohrady
Prague, 100 00, Czechia
Institute of Hematology and Blood Transfusion
Prague, 12800, Czechia
Saint-Louis Hospital, Department of Adult Hematology
Paris, Paris, 75010, France
Amiens Picardie University Hospital - South
Amiens, 59037, France
Angers University Hospital Center
Angers, France
Lille Regional University Hospital Center
Lille, 59037, France
South Lyon Hospital Center
Lyon, 69310, France
Leon Berard Center
Lyon, France
Nantes University Hospital Center - Hotel Dieu Hospital
Nantes, 44000, France
Archet 1 and 2 hospital
Nice, 06200, France
Nimes University Hospital Center, Department of Clinical Hematology and Medical Oncology
Nîmes, 30900, France
Bordeaux University Hospital
Pessac, France
University Hospital Center of Poitiers
Poitiers, France
Strasbourg Europe Institut of Cancerology
Strasbourg, 67200, France
University Hospital of Toulouse, IUCT-Oncopole
Toulouse, France
Tours Regional University Hospital Center
Tours, 37000, France
JSC Vian
Kutaisi, 4600, Georgia
JSC German Hospital
Tbilisi, 0119, Georgia
LEPL The First University Clinic of Tbilisi State Medical University
Tbilisi, 0141, Georgia
Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLC
Tbilisi, 0144, Georgia
JSC K. Eristavi National Center of Experimental and Clinical Surgery
Tbilisi, 0159, Georgia
Caucasus Medical Centre LLC
Tbilisi, 0186, Georgia
Marien Hospital Duesseldorf GmbH
Düsseldorf, 40479, Germany
University Hospital Freiburg
Freiburg im Breisgau, 79106, Germany
University Hospital Halle (Saale)
Halle, 06120, Germany
University Hospital Hamburg-Eppendorf
Hamburg, 20246, Germany
Hannover Medical School
Hanover, Germany
University Hospital Heidelberg
Heidelberg, 69120, Germany
University Hospital Jena
Jena, 07747, Germany
University Hospital Schleswig-Holstein
Kiel, 24105, Germany
MVZ Mitte Am Johannisplatz
Leipzig, 04103, Germany
Hospital Rechts der Isar
Munich, 81675, Germany
Staufer Schwaebisch Gmuend Hospital
Mutlangen, 73557, Germany
Hospital Nuernberg, Campus North
Nuremberg, 90419, Germany
Robert-Bosch-Hospital
Stuttgart, 70376, Germany
University Hospital Ulm
Ulm, 89081, Germany
General Hospital of Athens Laikon
Athens, 115 27, Greece
University General Hospital "Attikon"
Athens, PC 12462, Greece
University General Hospital of Ioannina
Ioannina, Greece
University General Hospital of Patras
Pátrai, 26504, Greece
General Hospital of Thessaloniki "G. Papanikolaou"
Thessaloniki, PC 57010, Greece
Semmelweis University
Budapest, H-1088, Hungary
Szabolcs-Szatmar-Bereg County Teaching Hospital
Nyíregyháza, 4400, Hungary
Tolna County Hospital
Szekszárd, H-7100, Hungary
Fejer County St. Gyorgy University Teaching Hospital
Székesfehérvár, Hungary
National Hospital SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Italy
Marche University Hospital
Ancona, 60126, Italy
Polyclinic S. Orsola-Malpighi
Bologna, 40138, Italy
ASST Spedali Civili Brescia
Brescia, Italy
University Hospital "G.Rodolico - San Marco"
Catania, Italy
Careggi University Hospital
Florence, 50134, Italy
Institute of Romagna for Cancer Research " Dino Amadori" - IRCCS IRST
Forlì, 47014, Italy
Maggiore Polyclinic Hospital, Foundation IRCCS Ca' Granda
Milan, 20122, Italy
European Institute of Oncology (IEO), IRCCS
Milan, Italy
University Hospital "Maggiore della Carita" of Novara
Novara, 28100, Italy
University Hospital San Luigi Gonzaga
Orbassano, Italy
University Polyclinic Hospital "Paolo Giaccone" Palermo
Palermo, Italy
Polyclinic San Matteo, IRCCS
Pavia, Italy
Local Health Company of Pesaro and Urbino
Pesaro, 61121, Italy
Hospital Arcispedale S. Maria Nuova of Reggio Emilia
Reggio Emilia, Italy
Hospital S. Eugenio- Rome 2 ASL
Rome, Italy
City of Health and Science of Turin
Turin, 10126, Italy
ASST Sette Laghi Hospital
Varese, Italy
"InterHem" General Partnership
Bialystok, Poland
University Teaching Centre, Hematology and Transplantology Clinic
Gdansk, Poland
Independent Public Healthcare Facility University Hospital in Krakow
Krakow, Poland
Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center
Lodz, 93-513, Poland
Jedrzej Sniadecki Specialist Hospital in Nowy Sacz
Nowy Sącz, 33 - 300, Poland
Oncology Center of Warmia and Mazury in Olsztyn
Olsztyn, Poland
AIDPORT
Poznan, 60-185, Poland
Dom Lekarski Medical Center Outlet Park
Szczecin, 70-784, Poland
Janusz Korczak Provincial Specialist Hospital
Słupsk, 76-200, Poland
Clinical Best Solutions LLC, Limited Partnership
Warsaw, 00-710, Poland
Dr Alfred Sokolowski Specialty Hospital
Wałbrzych, Poland
Jan Mikulicz-Radecki Teaching Hospital in Wroclaw
Wroclaw, Poland
Hospital Center of Baixo Vouga -Aveiro Unit - Hospital Infante D. Pedro
Aveiro, 3810- 501, Portugal
Braga Hospital
Braga, Portugal
Central Hospital of Western Lisbon
Lisbon, 1449-005, Portugal
Centro Hospitalar Lisboa Norte (CHLN) EPE - Hospital de Santa Maria
Lisbon, 1649-035, Portugal
Vila Nova de Gaia Central Hospital
Vila Nova de Gaia, Portugal
Onco Card Srl
Brasov, 500052, Romania
Colentina Clinical Hospital, Department of Hematology
Bucharest, 020125, Romania
"Prof. Dr. Ion Chiricuta" Institute of Oncology, Hematology Department
Cluj-Napoca, 400015, Romania
Bihor County Emergency Clinical Hospital, Department of Hematology
Oradea, 410469, Romania
Targu Mures County Emergency Clinical Hospital, Internal Medicine Department I, Hematology Unit
Târgu Mureş, 540136, Romania
University Clinical Center of Serbia
Belgrade, 11000, Serbia
Clinical Hospital Center Bezanijska Kosa
Belgrade, 7203, Serbia
University Clinical Center Kragujevac
Kragujevac, 34 000, Serbia
Clinical Center of Vojvodina
Novi Sad, Serbia
Inje University Busan Paik Hospital
Busan, 47392, South Korea
Pusan National University Hospital
Busan, 49241, South Korea
Kyungpook National University Hospital
Daegu, 41944, South Korea
Keimyung University - Dongsan Medical Center
Daegu, 42601, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Soon Chun Hyang University Hospital Seoul
Seoul, 04401, South Korea
Asan Medical Center
Seoul, 05505, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591, South Korea
University Hospital Germans Trias i Pujol
Badalona, 08916, Spain
University Hospital Vall d'Hebron
Barcelona, 08035, Spain
Catalan Institute of Oncology, Hospital Duran i Reynals
Barcelona, Spain
Caceres Hospital Complex - San Pedro de Alcantara General Hospital
Cáceres, 10003, Spain
Gran Canaria Dr Negrin University Hospital
Las Palmas de Gran Canaria, 35010, Spain
University Hospital 12 de Octubre
Madrid, 28041, Spain
University Hospital Ramon y Cajal
Madrid, 28041, Spain
University Hospital Virgen de la Victoria
Málaga, 29010, Spain
University Clinical Hospital of Salamanca
Salamanca, 37007, Spain
University Clinical Hospital of Valencia
Valencia, 46010, Spain
University and Polytechnic Hospital La Fe
Valencia, 46026, Spain
Quironsalud Zaragoza Hospital
Zaragoza, 50006, Spain
Birmingham Heartlands Hospital
Birmingham, B9 5SS, United Kingdom
Lincoln County Hospital
Boston, Lincoln County Hospital, United Kingdom
Pilgrim Hospital
Boston, PE21 9QS, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
University Hospital of Wales
Cardiff, CF14 4XW, United Kingdom
Western General Hospital, Lothian Health Board
Edinburgh, EH4 2XU, United Kingdom
Gloucestershire Royal Hospital
Gloucester, GL1 3NN, United Kingdom
Harrogate District Hospital
Harrogate, HG2 7SX, United Kingdom
Leicester Royal Infirmary
Leicester, LE1 5WW, United Kingdom
The Clatterbridge Cancer Center NHS Foundation Trust
Liverpool, L7 8YA, United Kingdom
University College Hospital
London, NW1 2PG, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
Genesis Care, Oxford
Oxford, OX4 6LB, United Kingdom
Genesis Care, Windsor
Windsor, SL4 3HD, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Placebo-controlled
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 21, 2024
First Posted
June 28, 2024
Study Start
June 3, 2024
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2028
Last Updated
September 25, 2025
Record last verified: 2024-10