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NCT06479135PHASE3Recruiting

Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

Kartos Therapeutics, Inc.

Start Date

6/3/2024

Completion Date

12/31/2028

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria for Ruxolitinib Alone Period: * 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 Exclusion Criteria for Ruxolitinib Alone Period: * 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 Inclusion Criteria for Randomized Period: * 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 Exclusion Criteria for Randomized Period: * 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

Interventions

DRUG

Navtemadlin

DRUG

Navtemadlin placebo

DRUG

Ruxolitinib

Interested in This Trial?

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Conditions

MyelofibrosisPost-PV MFPost-ET MyelofibrosisPrimary MyelofibrosisMF

Locations

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