Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis (TRANSFORM-1)

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Of Navitoclax In Combination With Ruxolitinib Versus Ruxolitinib In Subjects With Myelofibrosis (TRANSFORM-1)

Myelofibrosis is a type of bone marrow cancer that usually develops slowly and disrupts body's normal production of blood cells. It causes bone marrow scarring, leading to severe anemia that can cause weakness and fatigue. It can also cause a low number of blood-clotting cells called platelets, which increases risk of bleeding. Myelofibrosis often causes an enlarged spleen. The purpose of this study is to see if a combination of navitoclax and ruxolitinib is more effective and safe in assessment of change in spleen volume when compared to ruxolitinib in participants with myelofibrosis.

Navitoclax is an investigational drug for the treatment of myelofibrosis. Participants in this study are divided into two groups, called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of myelofibrosis will be enrolled. Around 230 participants will be enrolled in approximately 190 sites worldwide.

Participants will receive oral navitoclax tablet with oral ruxolitinib tablet or oral ruxolitinib tablet with oral placebo (no active drug) tablet and treatment may continue untill the participant cannot tolerate the study drug, or benefit is not achieved, or other reasons which qualify for discontinuation of the study drug.

There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, magnetic resonance imaging (MRI) or computed tomography (CT) scan, bone marrow tests, checking for side effects, and completing questionnaires.

Study Overview

• Status: Completed
• Conditions: Myelofibrosis (MF)
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Navitoclax; Drug: Placebo for Navitoclax

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • The Kinghorn Cancer Centre /ID# 221503
    • East Albury, New South Wales, Australia, 2640
      • Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 231311
    • Gosford, New South Wales, Australia, 2250
      • Gosford Hospital /ID# 221499
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital /ID# 221803
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Townsville University Hospital /ID# 229794
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Ctr /ID# 229795
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital /ID# 221501
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital /ID# 223203
• Austria
  • Vienna, Austria, 1140
    • Hanusch Krankenhaus /ID# 220909
  • Styria
    • Graz, Styria, Austria, 8010
      • Duplicate_Medizinische Universitaet Graz /ID# 220910
  • Upper Austria
    • Linz, Upper Austria, Austria, 4010
      • Ordensklinikum Linz GmbH Elisabethinen /ID# 220813
    • Wels, Upper Austria, Austria, 4600
      • Klinikum Wels-Grieskirchen GmbH /ID# 220901
  • Vienna
    • Vienna, Vienna, Austria, 1090
      • Medizinische Universitaet Wien /ID# 220906
• Belgium
  • Bruges, Belgium, 8000
    • AZ Sint-Jan Brugge /ID# 218805
  • Antwerpen
    • Antwerp, Antwerpen, Belgium, 2030
      • ZAS Cadix /ID# 221465
  • Liege
    • Liège, Liege, Belgium, 4000
      • CHU de Liège /ID# 218874
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • Université Catholique de Louvain-Namur - Centre Hospitalier Universitaire Dinant /ID# 221127
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 221125
    • Sint-Niklaas, Oost-Vlaanderen, Belgium, 9100
      • Vitaz /Id# 229861
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven /ID# 218806
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • AZ-Delta /ID# 221466
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT Dr Georgi Stranski EAD /ID# 231161
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sveti Georgi /ID# 231053
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Tokuda University Hospital EAD /ID# 231036
  • Sofia, Bulgaria, 1431
    • UMHAT Sveti Ivan Rilski /ID# 231028
  • Sofia
    • Sofiya, Sofia, Bulgaria, 1431
      • UMHAT Alexandrovska EAD /ID# 231056
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital /ID# 222636
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Cancer Centre /ID# 221752
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health - Oshawa /ID# 222080
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Niagara Health System /ID# 230994
  • Quebec
    • Québec, Quebec, Canada, G1J 1Z4
      • CHUQ- Hôpital de l'Enfant-Jesus /ID# 221754
• Croatia
  • City of Zagreb
    • Zagreb, City of Zagreb, Croatia, 10000
      • Clinical Hospital Dubrava /ID# 230795
    • Zagreb, City of Zagreb, Croatia, 10000
      • Klinicka bolnica Merkur /ID# 231155
    • Zagreb, City of Zagreb, Croatia, 10000
      • Klinicki bolnicki centar Zagreb /ID# 230793
  • Split-Dalmatia County
    • Split, Split-Dalmatia County, Croatia, 21000
      • Duplicate_Klinicki bolnicki centar Split /ID# 230796
• France
  • Angers, France, 49933
    • Chu Angers /Id# 219115
  • Paris, France, 75015
    • AP-HP - Hopital Necker /ID# 231318
  • Paris, France, 75010
    • Hôpital Saint-Louis /ID# 221288
  • Strasbourg, France, 67033
    • ICANS - Institut de Cancérologie Strasbourg Europe /ID# 229978
  • Gard
    • Nîmes, Gard, France, 30029
      • CHU NIMES - Hopital Caremeau /ID# 219114
  • Gironde
    • Pessac, Gironde, France, 33604
      • Centre Hospitalier Universitaire de Bordeaux /ID# 222518
  • Hauts-de-France
    • Roubaix, Hauts-de-France, France, 59100
      • CH Roubaix - Hopital Victor Provo /ID# 219116
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44000
      • CHU de Nantes, Hotel Dieu -HME /ID# 219113
  • Rhone
    • Pierre-Bénite, Rhone, France, 69495
      • HCL - Hopital Lyon Sud /ID# 222913
  • Savoie
    • Chambéry, Savoie, France, 73007
      • Centre Hospitalier Métropole Savoie - Site Hôpital de Chambéry /ID# 224506
  • Île-de-France Region
    • Bobigny, Île-de-France Region, France, 93000
      • Hopital Avicenne - APHP /ID# 221286
• Germany
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen /ID# 221522
  • Hamburg, Germany, 22081
    • OncoResearch Lerchenfeld GmbH /ID# 230867
  • Munich, Germany, 81675
    • Klinikum rechts der Isar /ID# 221520
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Universitatsklinikum Mannheim /ID# 221523
  • Bavaria
    • Munich, Bavaria, Germany, 81241
      • Haemato-Onkologie /ID# 221061
  • North Rhine-Westphalia
    • Aachen, North Rhine-Westphalia, Germany, 52074
      • Universitaetsklinikum Aachen /ID# 221519
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf /ID# 221347
• Greece
  • Athens, Greece, 10676
    • General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 230786
  • Attica
    • Athens, Attica, Greece, 11527
      • General Hospital of Athens Laiko /ID# 230785
    • Athens, Attica, Greece, 12462
      • Duplicate_University General Hospital Attikon /ID# 230784
• Israel
  • Central District
    • Kfar Saba, Central District, Israel, 4428164
      • Meir Medical Center /ID# 221374
    • Ẕerifin, Central District, Israel, 70300
      • Yitzhak Shamir Medical Center /ID# 222957
  • H_efa
    • Haifa, H_efa, Israel, 3109601
      • Rambam Health Care Campus /ID# 219120
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91120
      • Hadassah Medical Center-Hebrew University /ID# 219110
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 219137
    • Tel Aviv, Tel Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 219134
• Italy
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII /ID# 221907
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia /ID# 241273
  • Catania, Italy, 95123
    • AOU Policlinico G. Rodolico - San Marco /ID# 219085
  • Varese, Italy, 21100
    • Duplicate_ASST Sette Laghi /ID# 219084
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 220867
  • Firenze
    • Florence, Firenze, Italy, 50134
      • Azienda Ospedaliero Universitaria Careggi /ID# 219086
  • Roma
    • Rome, Roma, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 219083
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 453-8511
      • Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital /ID# 239100
    • Toyoake, Aichi-ken, Japan, 470-1192
      • Fujita Health University Hospital /ID# 221537
  • Chiba
    • Chiba, Chiba, Japan, 260-8677
      • Duplicate_Chiba University Hospital /ID# 239345
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 226093
  • Ehime
    • Toon-shi, Ehime, Japan, 791-0295
      • Ehime University Hospital /ID# 221443
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 221783
  • Fukushima
    • Fukushima, Fukushima, Japan, 960-1295
      • Fukushima Medical University Hospital /ID# 222752
  • Gifu
    • Ogaki-shi, Gifu, Japan, 503-8502
      • Ogaki Municipal Hospital /ID# 240173
  • Gunma
    • Maebashi, Gunma, Japan, 371-0821
      • Gunmaken Saiseikai Maebashi Hospital /ID# 242806
    • Maebashi, Gunma, Japan, 371-8511
      • Gunma University Hospital /ID# 221480
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Duplicate_Hokkaido University Hospital /ID# 242667
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0017
      • Kobe University Hospital /ID# 246236
  • Ibaraki
    • Hitachi-shi, Ibaraki, Japan, 317-0077
      • Hitachi General Hospital /ID# 240048
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital /ID# 238424
  • Kagoshima-ken
    • Kanoya-shi, Kagoshima-ken, Japan, 893-0024
      • Medical Corporation Seijinkai Ikeda Hospital /ID# 242172
  • Kyoto
    • Kyoto, Kyoto, Japan, 606-8507
      • Kyoto University Hospital /ID# 238423
  • Mie-ken
    • Tsu, Mie-ken, Japan, 514-8507
      • Mie University Hospital /ID# 221664
  • Miyazaki
    • Miyazaki, Miyazaki, Japan, 889-1692
      • University of Miyazaki Hospital /ID# 221483
  • Okayama-ken
    • Kurashiki-shi, Okayama-ken, Japan, 701-0192
      • Duplicate_Kawasaki Medical School Hospital /ID# 221481
    • Kurashiki-shi, Okayama-ken, Japan, 710-8602
      • Kurashiki Central Hospital /ID# 221692
  • Osaka
    • Hirakata-shi, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital /ID# 221482
    • Osakasayama-shi, Osaka, Japan, 589-8511
      • Kindai University Hospital /ID# 221479
    • Suita-shi, Osaka, Japan, 565-0871
      • The University of Osaka Hospital /ID# 221478
  • Saitama
    • Koshigaya, Saitama, Japan, 343-0845
      • Dokkyo Medical University Saitama Medical Center /ID# 222333
  • Shizuoka
    • Izunokuni-shi, Shizuoka, Japan, 410-2295
      • Juntendo University Shizuoka Hospital /ID# 221782
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital /ID# 221405
    • Bunkyo-ku, Tokyo, Japan, 113-8602
      • Nippon Medical School Hospital /ID# 221674
  • Yamanashi
    • Chuo-shi, Yamanashi, Japan, 409-3821
      • University of Yamanashi Hospital /ID# 221701
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen /ID# 218947
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht /ID# 218949
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud Universitair Medisch Centrum /ID# 218948
  • South Holland
    • Dordrecht, South Holland, Netherlands, 3318 AT
      • Albert Schweitzer Ziekenhuis /ID# 224015
• New Zealand
  • Auckland
    • Papatoetoe, Auckland, New Zealand, 2025
      • Aotearoa Clinical Trials /ID# 230770
• Russia
  • Saint Petersburg, Russia, 191024
    • Russian Research Institute of Hematology and Transfusiology of the FMBA /ID# 221029
  • Saint Petersburg, Russia, 194291
    • Leningrad Regional Clinical Hospital /ID# 221028
  • Saint Petersburg, Russia, 197341
    • Almazov National Medical Research Centre /ID# 221033
  • Tula, Russia, 300053
    • Tula Regional Clinical Hospital /ID# 221027
  • Moscow
    • Moscow, Moscow, Russia, 125284
      • Moscow State budget healthcare /ID# 221025
  • Murmansk Oblast
    • Petrozavodsk, Murmansk Oblast, Russia, 185019
      • Republican hospital named after V.A. Baranov /ID# 221412
  • Stavropol Kray
    • Pyatigorsk, Stavropol Kray, Russia, 357502
      • Clinic UZI 4D /ID# 221024
• Serbia
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • University Clinical Center Serbia /ID# 230854
    • Belgrade, Beograd, Serbia, 11080
      • Clin Hosp Ctr Bezanijska Kosa /ID# 230946
  • Sumadijski Okrug
    • Kragujevac, Sumadijski Okrug, Serbia, 34000
      • University Clinical Center Kragujevac /ID# 230855
  • Vojvodina
    • Novi Sad, Vojvodina, Serbia, 21000
      • Duplicate_Clinical Center Vojvodina /ID# 230853
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1864
      • Wits Clinical Research /ID# 232072
    • Johannesburg, Gauteng, South Africa, 2193
      • Duplicate_Wits Clinical Research Site /ID# 232071
    • Pretoria, Gauteng, South Africa, 0044
      • Alberts Cellular Therapy /ID# 232073
• South Korea
  • Busan Gwang Yeogsi
    • Busan, Busan Gwang Yeogsi, South Korea, 47392
      • Duplicate_Inje University Busan Paik Hospital /ID# 231667
    • Busan, Busan Gwang Yeogsi, South Korea, 49241
      • Pusan National University Hospital /ID# 222087
  • Daegu Gwang Yeogsi
    • Daegu, Daegu Gwang Yeogsi, South Korea, 41944
      • Duplicate_Kyungpook National University Hospital /ID# 231666
  • Gyeonggido
    • Incheon, Gyeonggido, South Korea, 21565
      • Gachon University Gil Medical Center /ID# 222089
    • Seongnam, Gyeonggido, South Korea, 13620
      • Duplicate_Seoul National University Bundang Hospital /ID# 219053
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Seoul National University Hospital /ID# 219055
    • Seoul, Seoul Teugbyeolsi, South Korea, 05505
      • Asan Medical Center /ID# 219054
    • Seoul, Seoul Teugbyeolsi, South Korea, 06351
      • Samsung Medical Center /ID# 221068
    • Seoul, Seoul Teugbyeolsi, South Korea, 06591
      • The Catholic University of Korea, Seoul St. Marys Hospital /ID# 219056
• Spain
  • Barcelona, Spain, 08003
    • Hospital Parc de Salut del Mar /ID# 220913
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron /ID# 229690
  • Madrid, Spain, 28027
    • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 230721
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal /ID# 220877
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 229691
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria /ID# 220878
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia /ID# 220875
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Duplicate_Hospital Clínico Universitario de Santiago-CHUS /ID# 222264
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol /ID# 229936
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35019
      • Hospital Universitario Dr. Negrin /ID# 220897
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra - Pamplona /ID# 230720
• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, 221 41
      • Duplicate_Skane University Hospital Lund /ID# 220835
  • Västra Götaland County
    • Gothenburg, Västra Götaland County, Sweden, 413 45
      • Duplicate_Sahlgrenska University Hospital /ID# 218776
  • Örebro County
    • Örebro, Örebro County, Sweden, 701 85
      • Orebro Universitetssjukhuset /ID# 220829
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital /ID# 218978
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 221146
  • Taoyuan, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital /ID# 218983
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 833
      • Kaohsiung Chang Gung Memorial Hospital /ID# 218984
  • Tainan
    • Tainan, Tainan, Taiwan, 73657
      • Chi Mei Hospital - Liouying /ID# 221145
  • Taipei
    • Taipei City, Taipei, Taiwan, 100
      • National Taiwan University Hospital /ID# 218976
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe University Medical Faculty /ID# 230759
  • Edirne, Istanbul, Turkey (Türkiye), 22030
    • Trakya University Medical Facu /ID# 230754
  • Istanbul, Turkey (Türkiye), 34214
    • Bagcilar Medipol Mega Universite Hastanesi /ID# 230757
  • Izmir, Turkey (Türkiye), 35040
    • Ege University Medical Faculty /ID# 230753
  • Malatya, Turkey (Türkiye), 44280
    • Inonu University Medical Faculty /ID# 230758
• Ukraine
  • Kyiv, Ukraine, 03143
    • Feofaniya Clinical Hospital of State Management of Affairs /ID# 232370
  • Kyiv, Ukraine, 02091
    • Medical Center OK Clinic LLC, International Institute of Clinical Research /ID# 230834
  • Lviv, Ukraine, 79044
    • SI Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine /ID# 230833
  • Kharkivs’ka Oblast’
    • Kharkiv, Kharkivs’ka Oblast’, Ukraine, 61070
      • Communal non-profit enterprise Regional Center of Oncology /ID# 230832
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust /ID# 221333
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital /ID# 219191
  • Greater London
    • London, Greater London, United Kingdom, SE1 9RT
      • Guys and St Thomas NHS Foundation Trust /ID# 219185
  • Lincolnshire
    • Lincoln, Lincolnshire, United Kingdom, LN2 4AX
      • United Lincolnshire Hospitals NHS Trust /ID# 231471
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Oxford University Hospitals NHS Foundation Trust /ID# 219192
• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group, PA /ID# 221824
  • California
    • Fullerton, California, United States, 92835
      • Providence - St. Jude Medical Center /ID# 241646
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at UC San Diego /ID# 218012
  • Colorado
    • Littleton, Colorado, United States, 80120
      • Rocky Mountain Cancer Centers - Littleton /ID# 222562
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute, Boca /ID# 230687
    • Fort Myers, Florida, United States, 33901-8108
      • Florida Cancer Specialist - South /ID# 221726
    • St. Petersburg, Florida, United States, 33705-1449
      • Florida Cancer Specialists - North /ID# 221727
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists - East /ID# 221728
  • Georgia
    • Atlanta, Georgia, United States, 30322-1013
      • Duplicate_Emory University /ID# 221562
    • Augusta, Georgia, United States, 30912-0003
      • Augusta University Georgia Cancer Center /ID# 221551
    • Columbus, Georgia, United States, 31904-8915
      • Columbus Regional Research Institute /ID# 227272
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Duplicate_Rush University Medical Center /ID# 221581
    • Normal, Illinois, United States, 61761
      • Mid Illinois Hematology & Oncology Associates, Ltd /ID# 224204
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood & Marrow Transpl /ID# 221586
  • Kansas
    • Fairway, Kansas, United States, 66205-2528
      • University of Kansas Cancer Center /ID# 218144
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital /ID# 221559
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center /ID# 224261
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute /ID# 218010
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5000
      • University of Michigan /ID# 221658
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Oncology Hematology /ID# 227357
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • MidAmerica Division, Inc. /ID# 221743
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Univ Med Ctr /ID# 221654
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health - Monter Cancer Center /ID# 222996
    • New York, New York, United States, 10065
      • Weill Cornell Medical College /ID# 220933
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research /ID# 230488
    • Cincinnati, Ohio, United States, 45236-2725
      • Oncology Hematology Care, Inc. /ID# 222556
    • Columbus, Ohio, United States, 43210
      • The Ohio State University /ID# 221584
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Ctr /ID# 218134
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Ctr /ID# 231689
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center /ID# 217994
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Northeast Texas /ID# 241813
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Salt Lake Clinic /ID# 221961
    • Salt Lake City, Utah, United States, 84112-5500
      • University of Utah /ID# 221009
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists - Fairfax /ID# 242682
  • Washington
    • Seattle, Washington, United States, 98108-1597
      • VA Puget Sound Health Care System /ID# 231691

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented diagnosis of Primary MyeloFibrosis (MF) as defined by World Health Organization (WHO) classification or Secondary MF (post polycythemia vera [PPV] - MF or Post Essential Thrombocythemia [PET] - MF) .

• Must be able to complete the MF Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days immediately preceding the date of randomization.

  -- Must have at least 2 symptoms with a score >=3 or a total score of >=12, as measured by the MFSAF v4.0.

• Classified as intermediate-2, or high-Risk MF as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
• Has splenomegaly defined as spleen palpation measurement >= 5 centimeters (cm) below costal margin or spleen volume greater than or equal to 450 cubic cm as assessed centrally by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
• Ineligible for stem cell transplantation at time of study entry due to age, comorbidities, or unfit for unrelated or unmatched donor transplant and other criteria per National Comprehensive Cancer Network guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Exclusion Criteria:

• Prior treatment with a Janus Kinase-2 (JAK-2) inhibitor.
• Prior treatment with a B-cell lymphoma 2 homology 3 (BH3)-mimetic compound or bromodomain and extra-terminal motif (BET) inhibitor or stem cell transplant.
• Receiving medication that interferes with coagulation or platelet function within 3 days prior to the first dose of study drug or during the study treatment period except for low dose aspirin (up to 100 milligram daily) and low molecular weight heparin (LMWH).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo for Navitoclax + Ruxolitinib; Placebo for navitoclax tablets were administered orally once daily (QD) per Baseline platelet count (>150 × 10^9/L starting dose of 200 mg; ≤150 × 10^9/L starting dose of 100 mg, which could be increased to 200 mg QD after 7 days provided platelet count is ≥75 × 10^9/L). Placebo for navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 25, Day 1 visit, placebo for navitoclax dose may be increased to 300 mg QD at Investigator's discretion for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Ruxolitinib tablets were administered orally twice daily (BID) per Baseline platelet count (>200 × 10^9/L starting dose of 20 mg; 100-200 × 10^9/L starting dose of 15 mg). Participants will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first).	Drug: Ruxolitinib; Tablet; Oral; Other Names: Jakafi; Drug: Placebo for Navitoclax; Film-coated tablet; Oral
Experimental: Navitoclax + Ruxolitinib; Navitoclax tablets were administered orally once daily (QD) per Baseline platelet count (>150 × 10^9/L starting dose of 200 mg; ≤150 × 10^9/L starting dose of 100 mg, which could be increased to 200 mg QD after 7 days provided platelet count is ≥75 × 10^9/L). Navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 25, Day 1 visit, navitoclax dose may be increased to 300 mg QD at Investigator's discretion for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Ruxolitinib tablets were administered orally twice daily (BID) per Baseline platelet count (>200 × 10^9/L starting dose of 20 mg; 100-200 × 10^9/L starting dose of 15 mg). Participants will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first).	Drug: Ruxolitinib; Tablet; Oral; Other Names: Jakafi; Drug: Navitoclax; Film-coated tablet; Oral; Other Names: ABT-263

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume at Week 24 (SVR35W24)	Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Symptom Score (TSS) at Week 24 as Measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0	TSS is assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0. Participants complete a symptom diary and rate the following seven MF symptoms: fatigue, night sweats, abdominal discomfort, pruritus, pain under the ribs on the left side, early satiety, and bone pain daily using a scale from 0 (absent) to 10 (worst imaginable), and the scores are averaged over 7 days, with a minimum of 4 days required to calculate the average score. Participants for whom a valid average score cannot be calculated either at baseline or post-baseline are considered non-responders. The TSS reflects the sum of the scores of these symptoms, for a maximum possible score of 70 (i.e., most severe symptom experience). Negative changes from Baseline indicate improvement.	Baseline, Week 24
Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume (SVR35) at Any Time	Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.	Up to Week 97
Duration of 35% Spleen Volume Reduction (SVR35)	Duration of SVR35 is defined as the time between the date of first response of spleen volume reduction of 35% achievement to the date of the first assessment where the spleen volume is less than 35% reduction from Baseline and is at least 25% increase from the nadir (the lowest spleen volume), confirmed relapse, or leukemic transformation per International Working Group (IWG) criteria, whichever is earlier.	Baseline (Week 0) Up to Month 48
Change From Baseline In Fatigue at Week 24 as Measured by the PROMIS Fatigue Short Form (SF) 7a	The PROMIS Fatigue SF 7a is a 7-item patient-reported outcome measure that assesses the impact and experience of participants with fatigue over the past 7 days. Each item is scored on a 5-point Likert scale (1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, and 5 = Always). Raw scores range from 7 to 35 and are subsequently transformed into a standardized T-score using the PROMIS wave 1 calibration (where a score of 50 represents the U.S. general population mean with a standard deviation of 10). Higher T-scores indicate greater fatigue severity. A decrease in T-score from Baseline represents a clinical improvement in fatigue symptoms.	Baseline, Week 24
Change From Baseline at Week 24 in Physical Functioning as Measured by the Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30	EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a physical functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the physical functioning scale indicates a better level of functioning, and positive changes from Baseline indicate improvement.	Baseline, Week 24
Percentage of Participants Achieving Anemia Response	For a participant who is transfusion independent (TI) at Baseline with hemoglobin value < 10 g/dL, anemia response is achieved if the post-Baseline hemoglobin level increases by ≥2 g/dL without receiving packed red blood cells (PRBC) transfusion (for any reason) within 2 weeks and without any erythropoietin or mimetics within the last 4 weeks prior to the increase in hemoglobin level by ≥2g/dL was observed. Hemoglobin values more than 30 days after the last dose of study treatment or after the start of post-study treatment or disease progression, whichever is earlier, will not be considered in the analysis of anemia response. For a participant who is transfusion dependent (TD) at Baseline, anemia response is defined as a period of at least 12 consecutive weeks without PRBC transfusion at any time after the first dose of study drug and on or prior to 30 days post last dose of study drug, the start of post-study treatment, disease progression or death, whichever occurs earlier.	Up to Week 97
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death from any cause.	Up to 50 months
Leukemia-Free Survival	Leukemia-free survival is defined as the number of days from the date of randomization to the onset date of documented leukemia, disease progression due to leukemia, or death due to leukemia, whichever occurs first.	Up to 50 months
Percentage of Participants Who Achieved Reduction in Grade of Bone Marrow Fibrosis From Baseline at Any Time	Change in grade of bone marrow fibrosis was measured per the European consensus grading system through bone marrow biopsy. The percentage of participants who achieved reduction of at least 1 grade in bone marrow fibrosis compared to Baseline is reported.	Up to Week 97

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Actual): April 13, 2023
• Study Completion (Actual): January 29, 2025

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 15, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Ruxolitinib; Myelofibrosis; Navitoclax; ABT-263; TRANSFORM-1
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Hemic and Lymphatic Diseases; Neoplasms; Primary Myelofibrosis; Antineoplastic Agents; ruxolitinib; navitoclax
• Other Study ID Numbers: M16-191; 2020-000097-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No