Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet Versus Best Available Therapy to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis (TRANSFORM-2)

Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Navitoclax in Combination With Ruxolitinib Versus Best Available Therapy in Subjects With Relapsed/Refractory Myelofibrosis (TRANSFORM-2), Incorporating Extension Arm C - Continued Access for Navitoclax to Roll Over Subjects From Studies M10-166, M16-109, M16-191, and M19-753

Myelofibrosis (MF) is a rare blood cancer, notable for scarring of the bone marrow (the spongy tissue inside bones) and the spleen becoming larger. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, compared to best available therapy, for adult participants with MF.

Navitoclax is an investigational drug (not yet approved) being developed for the treatment of MF. Participants in this study will be randomly selected (like picking numbers out of a hat) to be in 1 of 2 treatment arms. Neither participants nor the study doctor will be able to pick which treatment arm a participants enters. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. In Arm C, participants will receive navitoclax. Adult participants with a diagnosis of MF that came back or did not get better after earlier treatment will be enrolled. Approximately 330 participants will be enrolled in approximately 322 sites across the world.

In Arm A, participants will receive navitoclax tablet by mouth once daily with by mouth ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT available to the investigator. In Arm C, participants will receive navitoclax tablet by mouth once daily. Participants will receive the study drug until they experience no benefit (determined by the investigator), participants cannot tolerate the study drugs, or participants withdraw consent. The approximate treatment duration is about 3 years.

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

Study Overview

• Status: Active, not recruiting
• Conditions: Myelofibrosis (MF)
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Navitoclax; Drug: Best Available Therapy (BAT)

• Study Type: Interventional
• Enrollment (Estimated): 330
• 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# 221097
    • East Albury, New South Wales, Australia, 2640
      • Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 223848
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle /ID# 224324
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital /ID# 221096
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital /ID# 221099
• Austria
  • Vienna, Austria, 1140
    • Hanusch Krankenhaus /ID# 220912
  • Lower Austria
    • Sankt Pölten, Lower Austria, Austria, 3100
      • Universitaetsklinikum St. Poelten /ID# 221709
  • Styria
    • Graz, Styria, Austria, 8010
      • Medizinische Universitaet Graz /ID# 220919
  • Upper Austria
    • Linz, Upper Austria, Austria, 4010
      • Ordensklinikum Linz GmbH Elisabethinen /ID# 220914
    • Wels, Upper Austria, Austria, 4600
      • Klinikum Wels-Grieskirchen GmbH /ID# 220915
  • Vienna
    • Vienna, Vienna, Austria, 1090
      • Medizinische Universitaet Wien /ID# 220911
• Belgium
  • Antwerpen
    • Antwerp, Antwerpen, Belgium, 2030
      • ZAS Cadix /ID# 221468
  • Brussels Capital
    • Brussels, Brussels Capital, Belgium, 1200
      • Cliniques Universitaires UCL Saint-Luc /ID# 224221
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6280
      • Grand Hôpital de Charleroi - Les Viviers /ID# 224827
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 220841
    • Sint-Niklaas, Oost-Vlaanderen, Belgium, 9100
      • Vitaz /Id# 228150
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • AZ-Delta /ID# 221469
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT Dr Georgi Stranski EAD /ID# 231650
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Tokuda University Hospital EAD /ID# 231649
  • Sofia, Bulgaria, 1431
    • UMHAT Sveti Ivan Rilski /ID# 231651
  • Varna, Bulgaria, 9010
    • UMHAT Sveta Marina /ID# 234119
  • Sofia
    • Sofiya, Sofia, Bulgaria, 1431
      • UMHAT Alexandrovska EAD /ID# 231652
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Cancer Centre /ID# 220887
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute /ID# 238858
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network_Princess Margaret Cancer Centre /ID# 253942
  • Quebec
    • Lévis, Quebec, Canada, G6V 3Z1
      • CISSS-CA (Centre Integre de sante et de services sociaux de Chaudiere-Appalache) /ID# 222433
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre - Glen Site /ID# 222614
    • Québec, Quebec, Canada, G1J 1Z4
      • CHUQ- Hôpital de l'Enfant-Jesus /ID# 220888
• Croatia
  • City of Zagreb
    • Zagreb, City of Zagreb, Croatia, 10000
      • Clinical Hospital Dubrava /ID# 230801
    • Zagreb, City of Zagreb, Croatia, 10000
      • Klinicka bolnica Merkur /ID# 230799
    • Zagreb, City of Zagreb, Croatia, 10000
      • Klinicki bolnicki centar Zagreb /ID# 230798
  • County of Osijek-Baranja
    • Osijek, County of Osijek-Baranja, Croatia, 31000
      • Klinicki bolnicki centar Osijek /ID# 231503
  • Split-Dalmatia County
    • Split, Split-Dalmatia County, Croatia, 21000
      • Klinicki Bolnicki Centar (KBC) Split /ID# 230800
• Czechia
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze /ID# 220969
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 625 00
      • Fakultní Nemocnice Brno - Jihlavská /ID# 220959
• Denmark
  • North Denmark
    • Aalborg, North Denmark, Denmark, 9000
      • Aalborg University Hospital /ID# 224391
  • Region Sjælland
    • Roskilde, Region Sjælland, Denmark, 4000
      • Roskilde Sygehus /ID# 224456
• France
  • Angers, France, 49933
    • Chu Angers /Id# 219129
  • Paris, France, 75010
    • Hôpital Saint-Louis /ID# 221390
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06200
      • Duplicate_CHU DE NICE-HOPITAL LARCHET II /ID# 256291
  • Gard
    • Nîmes, Gard, France, 30029
      • CHU NIMES - Hopital Caremeau /ID# 219128
  • Gironde
    • Pessac, Gironde, France, 33604
      • Centre Hospitalier Universitaire de Bordeaux /ID# 222696
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44000
      • CHU de Nantes, Hotel Dieu -HME /ID# 219127
  • Rhone
    • Pierre-Bénite, Rhone, France, 69495
      • HCL - Hopital Lyon Sud /ID# 222695
  • Savoie
    • Chambéry, Savoie, France, 73007
      • Centre Hospitalier Métropole Savoie - Site Hôpital de Chambéry /ID# 223771
  • Île-de-France Region
    • Bobigny, Île-de-France Region, France, 93000
      • Hopital Avicenne - APHP /ID# 221287
• Germany
  • Hamburg, Germany, 22081
    • OncoResearch Lerchenfeld GmbH /ID# 225034
  • Munich, Germany, 81675
    • Klinikum rechts der Isar /ID# 221526
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Universitatsklinikum Mannheim /ID# 221529
    • Mutlangen, Baden-Wurttemberg, Germany, 73557
      • Stauferklinikum Schwaebisch Gmuend /ID# 223948
  • Bavaria
    • Augsburg, Bavaria, Germany, 86150
      • Gemeinschaftspraxis Dr. Heinrich und Prof. Bangerter /ID# 225025
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18057
      • Universitaetsmedizin Rostock /ID# 224157
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44791
      • Augusta-Kranken-Anstalt gGmbH, Bochum-Mitte /ID# 224695
  • Saxony
    • Chemnitz, Saxony, Germany, 09116
      • Klinikum Chemnitz gGmbH /ID# 224575
    • Dresden, Saxony, Germany, 01307
      • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf /ID# 221346
• Greece
  • Athens, Greece, 10676
    • General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 221179
  • RION Patras Achaia, Greece, 26504
    • University General Hospital of Patras /ID# 221178
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki George Papanikolaou /ID# 221463
  • Achaia
    • Pátrai, Achaia, Greece, 25443
      • Olympion General Clinic /ID# 261423
  • Attica
    • Athens, Attica, Greece, 11527
      • General Hospital of Athens Laiko /ID# 221175
• Hungary
  • Szeged, Hungary, 6720
    • Szegedi Tudományegyetem /ID# 220955
  • Fejér
    • Székesfehérvár, Fejér, Hungary, 8000
      • Fejér Vármegyei Szent György Egyetemi Oktató Kórház /ID# 220949
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Debreceni Egyetem-Klinikai Kozpont /ID# 220947
  • Somogy County
    • Kaposvár, Somogy County, Hungary, 7400
      • Somogy Varmegyei Kaposi Mor Oktato Korhaz /ID# 220948
  • Szabolcs-Szatmár-Bereg
    • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400
      • Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz /ID# 220946
• Israel
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center /ID# 219139
  • Central District
    • Ẕerifin, Central District, Israel, 70300
      • Yitzhak Shamir Medical Center /ID# 222972
  • H_efa
    • Afula, H_efa, Israel, 1834111
      • HaEmek Medical Center /ID# 220839
    • Haifa, H_efa, Israel, 3109601
      • Rambam Health Care Campus /ID# 219121
    • Haifa, H_efa, Israel, 34362
      • The Lady Davis Carmel Medical Center /ID# 222973
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91120
      • Hadassah Medical Center-Hebrew University /ID# 219111
    • Jerusalem, Jerusalem, Israel, 9765400
      • Hadassah Mt. Scopus /ID# 253394
  • Northern District
    • Nahariya, Northern District, Israel, 2210001
      • Galilee Medical Center /ID# 225280
  • Southern District
    • Ashdod, Southern District, Israel, 7747629
      • Duplicate_Assuta Ashdod Medical Center /ID# 225281
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 219136
    • Tel Aviv, Tel Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 219135
• Italy
  • Ancona, Italy, 60020
    • Azienda Ospedaliero Universitaria delle Marche /ID# 238438
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII /ID# 221222
  • Catania, Italy, 95123
    • AOU Policlinico G. Rodolico - San Marco /ID# 219089
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone /ID# 221078
  • Reggio Calabria, Italy, 89125
    • Grande Ospedale Metropolitano Bianchi - Melacrino - Morelli P.O. Riuniti /ID# 221220
  • Udine, Italy, 33100
    • Duplicate_University Hospital Santa Maria della Misericordia /ID# 221241
  • Varese, Italy, 21100
    • ASST Sette Laghi - Ospedale Di Circolo E Fondazione Macchi Varese /ID# 234183
  • Vicenza, Italy, 36100
    • Azienda ULSS 8 Berica /ID# 221079
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Duplicate_IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 221077
  • Firenze
    • Florence, Firenze, Italy, 50134
      • Azienda Ospedaliero Universitaria Careggi /ID# 219090
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Duplicate_Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Universita /ID# 219087
  • Monza E Brianza
    • Monza, Monza E Brianza, Italy, 20052
      • Fondazione IRCCS San Gerardo dei Tintori - Ospedale San Gerardo /ID# 225113
  • Napoli
    • Naples, Napoli, Italy, 80131
      • Azienda Ospedaliera Universitaria Federico II /ID# 224673
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • A.O.U. CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO - Ospedale Molinette /ID# 221223
  • Roma
    • Rome, Roma, Italy, 00161
      • Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 225731
• Japan
  • Tokyo, Japan, 108-8639
    • IMSUT Hospital, The Institute of Medical Science, The University of Tokyo /ID# 257944
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 453-8511
      • Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital /ID# 221150
    • Toyoake, Aichi-ken, Japan, 470-1192
      • Fujita Health University Hospital /ID# 221598
  • Aomori
    • Aomori, Aomori, Japan, 030-8553
      • Aomori Prefectural Central Hospital /ID# 221778
  • Chiba
    • Chiba, Chiba, Japan, 260-8677
      • Chiba University Hospital /ID# 224546
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 226653
  • Ehime
    • Toon-shi, Ehime, Japan, 791-0295
      • Ehime University Hospital /ID# 221158
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 221606
  • Fukushima
    • Fukushima, Fukushima, Japan, 960-1295
      • Fukushima Medical University Hospital /ID# 221877
  • Gifu
    • Gifu, Gifu, Japan, 501-1194
      • Gifu University Hospital /ID# 224371
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0006
      • Sapporo Hokuyu Hospital /ID# 221149
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0047
      • Kobe City Medical Center General Hospital /ID# 221156
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital /ID# 223028
  • Iwate
    • Shiwa-gun, Iwate, Japan, 028-3695
      • Iwate Medical University Hospital /ID# 222044
  • Kanagawa
    • Kamakura-shi, Kanagawa, Japan, 247-8533
      • Shonan Kamakura General Hospital /ID# 223030
  • Kumamoto
    • Kumamoto, Kumamoto, Japan, 862-8655
      • Kumamoto Shinto General Hospital /ID# 255645
  • Kyoto
    • Kyoto, Kyoto, Japan, 606-8507
      • Kyoto University Hospital /ID# 223008
  • Mie-ken
    • Tsu, Mie-ken, Japan, 514-8507
      • Mie University Hospital /ID# 221665
  • Miyazaki
    • Miyazaki, Miyazaki, Japan, 889-1692
      • University of Miyazaki Hospital /ID# 221821
  • Niigata
    • Niigata, Niigata, Japan, 951-8520
      • Niigata University Medical & Dental Hospital /ID# 223034
  • Okayama-ken
    • Kurashiki-shi, Okayama-ken, Japan, 710-8602
      • Kurashiki Central Hospital /ID# 221690
  • Osaka
    • Hirakata-shi, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital /ID# 257289
    • Suita-shi, Osaka, Japan, 565-0871
      • The University of Osaka Hospital /ID# 221159
  • Saitama
    • Koshigaya, Saitama, Japan, 343-0845
      • Dokkyo Medical University Saitama Medical Center /ID# 222334
  • Shizuoka
    • Izunokuni-shi, Shizuoka, Japan, 410-2295
      • Juntendo University Shizuoka Hospital /ID# 221780
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital /ID# 221154
    • Bunkyo-ku, Tokyo, Japan, 113-8602
      • Nippon Medical School Hospital /ID# 221676
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital /ID# 221540
    • Sumida-ku, Tokyo, Japan, 130-8575
      • Tokyo Metropolitan Bokutoh Hospital /ID# 254774
  • Yamanashi
    • Chuo-shi, Yamanashi, Japan, 409-3821
      • University of Yamanashi Hospital /ID# 221706
• New Zealand
  • Auckland
    • Papatoetoe, Auckland, New Zealand, 2025
      • Aotearoa Clinical Trials /ID# 232201
• Poland
  • Katowice, Poland, 40-519
    • Pratia Onkologia Katowice /ID# 224526
  • Greater Poland Voivodeship
    • Piła, Greater Poland Voivodeship, Poland, 64-920
      • ARS-MEDICAL Sp. z o.o. /ID# 238336
    • Poznan, Greater Poland Voivodeship, Poland, 60-569
      • Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola /ID# 241031
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-501
      • SP ZOZ Szpital Uniwersytecki w Krakowie /ID# 221160
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-081
      • Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie /ID# 221124
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 01-748
      • Lux Med Onkologia - Szpital Szamocka /Id# 221265
    • Warsaw, Masovian Voivodeship, Poland, 02-172
      • MTZ Clinical Research Powered by Pratia /ID# 221759
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • Uniwersyteckie Centrum Kliniczne /ID# 221298
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 93-513
      • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopern /ID# 221161
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Hospital del Centro Comprensivo de Cancer de la UPR /ID# 223281
• Russia
  • Moscow, Russia, 127644
    • Hospital n.a. V.V. Veresaev /ID# 225221
  • Saint Petersburg, Russia, 191024
    • Russian Research Institute of Hematology and Transfusiology of the FMBA /ID# 221115
  • Saint Petersburg, Russia, 197341
    • Almazov National Medical Research Centre /ID# 221114
  • Tula, Russia, 300053
    • Tula Regional Clinical Hospital /ID# 221302
  • Moscow
    • Moscow, Moscow, Russia, 125284
      • Moscow State budget healthcare /ID# 221116
  • Stavropol Kray
    • Pyatigorsk, Stavropol Kray, Russia, 357502
      • Clinic UZI 4D /ID# 221303
• Serbia
  • Novi Sad, Serbia, 21000
    • University Clinical Center Vojvodina /ID# 231057
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • University Clinical Center Serbia /ID# 231058
    • Belgrade, Beograd, Serbia, 11080
      • Clin Hosp Ctr Bezanijska Kosa /ID# 231059
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Duplicate_Wits Clinical Research Site /ID# 231554
    • Pretoria, Gauteng, South Africa, 0044
      • Alberts Cellular Therapy /ID# 231556
• South Korea
  • Busan Gwang Yeogsi
    • Busan, Busan Gwang Yeogsi, South Korea, 49241
      • Pusan National University Hospital /ID# 220980
  • Gyeonggido
    • Incheon, Gyeonggido, South Korea, 21565
      • Gachon University Gil Medical Center /ID# 220972
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Seoul National University Hospital /ID# 219060
    • Seoul, Seoul Teugbyeolsi, South Korea, 06351
      • Samsung Medical Center /ID# 221091
    • Seoul, Seoul Teugbyeolsi, South Korea, 06591
      • The Catholic University of Korea, Seoul St. Marys Hospital /ID# 219061
• Spain
  • Barcelona, Spain, 08003
    • Hospital Parc de Salut del Mar /ID# 220922
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron /ID# 240979
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves /ID# 253936
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 233726
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz /ID# 224813
  • Málaga, Spain, 29011
    • Hospital Regional Universitario de Malaga /ID# 221906
  • Salamanca, Spain, 37711
    • Hospital Universitario de Salamanca /ID# 221904
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio /ID# 221932
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia /ID# 220920
  • A Coruna
    • A Coruña, A Coruna, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña /ID# 224617
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Duplicate_Hospital Clínico Universitario de Santiago-CHUS /ID# 221616
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol /ID# 233727
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35019
      • Hospital Universitario Dr. Negrin /ID# 220923
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias /ID# 224815
• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, 224 84
      • Skane University Hospital Lund /ID# 220834
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Universitaetsspital Bern /ID# 223439
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4031
      • Duplicate_Universitätsspital Basel /ID# 221261
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 218980
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 271389
  • Taichung, Taiwan, 40447
    • China Medical University Hospital /ID# 218979
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital /ID# 271206
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 221147
  • Taoyuan, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital /ID# 218982
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 833
      • Kaohsiung Chang Gung Memorial Hospital /ID# 218985
  • Tainan
    • Tainan, Tainan, Taiwan, 73657
      • Chi Mei Hospital - Liouying /ID# 221144
  • Taipei
    • Taipei City, Taipei, Taiwan, 100
      • National Taiwan University Hospital /ID# 271207
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Askeri Tip Academy /ID# 224568
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universitesi Hastaneleri /ID# 271084
  • Edirne, Istanbul, Turkey (Türkiye), 22030
    • Trakya University Medical Facu /ID# 224572
  • Izmir, Turkey (Türkiye), 35040
    • Ege University Medical Faculty /ID# 224570
  • Mersin, Turkey (Türkiye), 33343
    • Mersin University Medical /ID# 224571
  • Samsun, Turkey (Türkiye), 55200
    • Ondokuz mayis University Facul /ID# 224567
  • Istanbul
    • Tuzla, Istanbul, Turkey (Türkiye), 34953
      • Medipol Mega Üniversite Hastanesi /ID# 271374
• Ukraine
  • Kyiv, Ukraine, 03143
    • Feofaniya Clinical Hospital of State Management of Affairs /ID# 271397
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust /ID# 221334
  • Edinburgh, United Kingdom, EH3 9HE
    • NHS Lothian /ID# 224378
  • Newcastle upon Tyne, United Kingdom, NE3 3HD
    • The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 221335
  • Greater London
    • London, Greater London, United Kingdom, SE1 9RT
      • Dup_Guys and St Thomas NHS Foundation Trust - Guy's Hospital /ID# 221041
  • Lincolnshire
    • Lincoln, Lincolnshire, United Kingdom, LN2 4AX
      • United Lincolnshire Hospitals NHS Trust /ID# 224613
  • Norfolk
    • Great Yarmouth, Norfolk, United Kingdom, NR31 6LA
      • James Paget University Hospitals NHS Foundation Trust /ID# 221219
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224-5665
      • Ironwood Cancer & Res Ctr /ID# 222162
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group, PA /ID# 221826
  • California
    • Duarte, California, United States, 91010
      • City of Hope /ID# 218996
    • Fullerton, California, United States, 92835
      • Providence - St. Jude Medical Center /ID# 271382
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at UC San Diego /ID# 219009
    • La Jolla, California, United States, 92037
      • Moores Cancer Center /ID# 271596
    • Long Beach, California, United States, 90806-1701
      • Long Beach Memorial Medical Ct /ID# 224542
    • Whittier, California, United States, 90603
      • Icri /Id# 221967
  • Colorado
    • Grand Junction, Colorado, United States, 81501-6132
      • St. Mary's Hospital Regional Cancer Center /ID# 224229
  • Georgia
    • Augusta, Georgia, United States, 30912-0003
      • Augusta University Georgia Cancer Center /ID# 219051
    • Columbus, Georgia, United States, 31904-8915
      • Columbus Regional Research Institute /ID# 224410
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center /ID# 271373
    • Elk Grove Village, Illinois, United States, 60007-3361
      • Northwest Oncology & Hematology - Elk Grove Village /ID# 222818
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Ctr /ID# 219048
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood & Marrow Transpl /ID# 221587
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-2600
      • Tulane Medical Center - New Orleans /ID# 222940
    • New Orleans, Louisiana, United States, 70121
      • Duplicate_Ochsner Clinic Foundation-New Orleans /ID# 222777
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Partners of Maryland /ID# 222836
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute /ID# 218998
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan /ID# 218463
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital /ID# 221190
    • Royal Oak, Michigan, United States, 48073-6710
      • William Beaumont Hospital /ID# 222705
  • Missouri
    • St Louis, Missouri, United States, 63110-2539
      • Saint Louis University Cancer Center /ID# 222287
  • New Jersey
    • Florham Park, New Jersey, United States, 07932-1049
      • Summit Medical Group-Florham Park /ID# 222620
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Univ Med Ctr /ID# 219047
  • New York
    • Greenvale, New York, United States, 11548-1219
      • The Cancer Institute at St. Francis Hospital /ID# 231782
    • New York, New York, United States, 10016-6028
      • Manhattan Hematology Oncology MHO Associates /ID# 223193
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 221081
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-0001
      • Atrium Health Wake Forest Baptist Medical Center /ID# 222899
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center /ID# 222650
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Pennsylvania Cancer Specialists & Research Institute /ID# 271376
    • Philadelphia, Pennsylvania, United States, 19104-4238
      • Hospital of the University of Pennsylvania /ID# 219001
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center /ID# 223955
  • Texas
    • Abilene, Texas, United States, 79606
      • Texas Oncology - Abilene - Antilley Road /ID# 271379
    • Houston, Texas, United States, 77030
      • Duplicate_Houston Methodist Hospital /ID# 223103
    • San Antonio, Texas, United States, 78229
      • University of Texas Health San Antonio MD Anderson Cancer Center /ID# 233942
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Salt Lake Clinic /ID# 221962
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists - Fairfax /ID# 223016
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Everett /ID# 223130
    • Yakima, Washington, United States, 98902-6388
      • Yakima Valley Memorial Hosp /ID# 224368
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • HSHS St. Vincent Hospital /ID# 224468

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Must complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of the 7 days immediately prior to the date of randomization and must agree to collect MFSAF data daily by ePRO device during the study collection window.

  -- Has at least 2 symptoms each with an average score >= 3 or an average total score of >= 12, as measured by the MFSAF v4.0.

• Documented diagnosis of primary myelofibrosis (MF) as defined by the World Health Organization (WHO) classification, post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF, characterized by bone marrow fibrosis grades 2 or 3.
• Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).

• Must currently be on treatment or have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):

  • Treatment with ruxolitinib for >= 24 weeks that was stopped due to lack of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status.

  • Treatment with ruxolitinib for < 24 weeks with documented disease progression while on therapy as defined by any of the following:

    • Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
    • A >= 100% increase in the palpable distance below the LCM in participants with measurable spleen distance 5 to 10 centimeters (cm) prior to the initiation of ruxolitinib.
    • A >= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance > 10 cm prior to the initiation of ruxolitinib.
    • A spleen volume increase of >= 25% (as assessed by Magnetic Resonance Imaging [MRI] or Computed Tomography [CT] scan) in participants with a spleen volume assessment prior to the initiation of ruxolitinib.
  • Prior treatment with ruxolitinib of at least 10 mg twice daily (BID) for >= 28 days with intolerance defined as new RBC transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily ruxolitinib dose of >= 30 mg but unable to reduce dose further due to lack of efficacy.

Note: Participant must not require a ruxolitinib dose less than 10 mg BID (20 mg daily) due to prior history of ruxolitinibrelated ≥ Grade 3 toxicity.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Splenomegaly defined as palpable spleen measurement >= 5 cm below left costal margin or spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.
• Baseline platelet count >= 100 × 10^9/L.

Exclusion Criteria:

• Received prior treatment with a B-cell lymphoma 2 homology 3 (BH3)-mimetic compound, bromodomain and extra-terminal (BET) inhibitor, phosphoinositide 3- kinase and telomerase inhibitors (e.g., parsaclisib), prior use of > 1 JAK2 inhibitor or stem cell transplant.
• Eligible for stem cell transplantation at the time of study entry.
• 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 mg daily) and low molecular weight heparin (LMWH).
• Receiving anticancer therapy for an active malignancy or MF including chemotherapy, radiation therapy, hormonal therapy such that at least 5 half-lives of that medication is completed at least 7 days prior to the first dose of study drug or within 30 days prior to first dose of study drug, whichever is shorter, and during the study treatment period (other than any overlapping therapy as part of the selected BAT).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Navitoclax + Ruxolitinib; Participants will receive navitoclax tablets once daily and ruxolitinib tablets twice daily.	Drug: Ruxolitinib; Tablet; Oral; Drug: Navitoclax; Tablet; Oral; Other Names: ABT-263
Active Comparator: Arm B: Best Available Therapy (BAT); Participants will receive one of the BAT options, per the investigator's discretion.	Drug: Best Available Therapy (BAT); Tablet/Capsule; Oral or Solution for Subcutaneous Injection
Experimental: Arm C: Continued Access for Navitoclax; Participants will receive navitoclax tablets once daily.	Drug: Navitoclax; Tablet; Oral; Other Names: ABT-263

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arms A and B: Percentage of Participants who achieve Spleen Volume Reduction of at least 35% 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.	At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arms A and B: Percentage of Participants who achieve at least 50% Reduction in Total Symptom Score (TSS)	Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	Baseline (Week 0) Up to Week 24
Arms A and B: Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at any time	Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.	Baseline (Week 0) Up to Week 97
Arms A and B: Percentage of Participants with Reduction in Grade of Bone Marrow Fibrosis	Reduction in grade of bone marrow fibrosis from baseline as measured by the European consensus grading system will be assessed.	Baseline (Week 0) Up to Week 97
Arms A and B: Percentage of Participants with Anemia Response	Anemia response per International Working Group (IWG) criteria will be assessed.	Baseline (Week 0) Up to Week 97
Arms A and B: Percentage of Participants with Overall Survival	Overall survival is defined as the time from start of study to the date of death from any cause.	Last Visit Up to 5 Years
Arms A and B: Percentage of Participants with Leukemia-free Survival	Leukemia free survival is the time from start of study to the date of development of leukemia.	Last Visit Up to 5 Years
Arms A and B: Percentage of Participants with Change in Fatigue	Change in fatigue will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a.	Baseline (Week 0) Up to Week 24
Arms A and B: Time to Deterioration of Physical Functioning	Time to deterioration of physical functioning is measured by the physical functioning domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, or death.	Baseline (Week 0) Up to Week 97
Arms A and B: Percentage of Participants with at Least 50% Reduction in TSS	At least 50% reduction in TSS from baseline (at any time) as measured by MFSAF v4.0.	Baseline (Week 0) Up to Week 97

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2020
• Primary Completion (Actual): January 29, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 10, 2020
• First Posted (Actual): July 13, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Ruxolitinib; Myelofibrosis; MF; Navitoclax; ABT-263
• 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: M20-178; 2023-507273-18-00 (Other Identifier: EU CT)

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.: Yes