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: Active, not recruiting
• Conditions: Myelofibrosis (MF)
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Navitoclax; Drug: Placebo for Navitoclax

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

Expanded Access

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 Regional Cancer Centre /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
      • Alfred Health /ID# 221501
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital /ID# 223203
• Austria
  • Wien, Austria, 1140
    • Hanusch Krankenhaus /ID# 220909
  • Oberoesterreich
    • Linz, Oberoesterreich, Austria, 4010
      • Ordensklinikum Linz GmbH Elisabethinen /ID# 220813
    • Wels, Oberoesterreich, Austria, 4600
      • Klinikum Wels-Grieskirchen GmbH /ID# 220901
  • Steiermark
    • Graz, Steiermark, Austria, 8010
      • Medizinische Universitaet Graz /ID# 220910
  • Wien
    • Vienna, Wien, Austria, 1090
      • Medizinische Universitaet Wien /ID# 220906
• Belgium
  • Antwerp, Belgium, 2060
    • ZNA Stuivenberg /ID# 221465
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Brugge /ID# 218805
  • Liege, Belgium, 4000
    • Centre Hospitalier Universitaire du Sart Tilman CHU de Liege /ID# 218874
  • Sint-Niklaas, Belgium, 9100
    • Vitaz /Id# 229861
  • Namur
    • Godinne, Namur, Belgium, 5530
      • CHU UCL Namur - site Godinne /ID# 221127
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 221125
  • 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
    • Quebec City, Quebec, Canada, G1J 1Z4
      • CHUQ- Hôpital de l'Enfant-Jesus /ID# 221754
• Croatia
  • Grad Zagreb
    • Zagreb, Grad Zagreb, Croatia, 10000
      • Clinical Hospital Dubrava /ID# 230795
    • Zagreb, Grad Zagreb, Croatia, 10000
      • Klinicka bolnica Merkur /ID# 231155
    • Zagreb, Grad Zagreb, Croatia, 10000
      • Klinicki bolnicki centar Zagreb /ID# 230793
  • Splitsko-dalmatinska Zupanija
    • Split, Splitsko-dalmatinska Zupanija, Croatia, 21000
      • Klinicki bolnicki centar Split /ID# 230796
• France
  • Angers, France, 49933
    • Chu Angers /Id# 219115
  • Paris, France, 75010
    • AP-HP - Hopital Saint-Louis /ID# 221288
  • Paris, France, 75015
    • AP-HP - Hopital Necker /ID# 231318
  • Strasbourg Cedex, France, 67033
    • ICANS - Institut de Cancérologie Strasbourg Europe /ID# 229978
  • Auvergne-Rhone-Alpes
    • Pierre Benite CEDEX, Auvergne-Rhone-Alpes, France, 69495
      • HCL - Hopital Lyon Sud /ID# 222913
  • Gard
    • Nimes CEDEX 9, Gard, France, 30029
      • CHU NIMES - Hopital Caremeau /ID# 219114
  • Gironde
    • Pessac, Gironde, France, 33604
      • CHU Bordeaux - Hopital Haut Leveque /ID# 222518
  • Hauts-de-France
    • Roubaix Cedex 1, Hauts-de-France, France, 59100
      • CH Roubaix - Hopital Victor Provo /ID# 219116
  • Ile-de-France
    • Bobigny, Ile-de-France, France, 93000
      • Hopital Avicenne - APHP /ID# 221286
  • Pays-de-la-Loire
    • Nantes, Pays-de-la-Loire, France, 44000
      • CHU de Nantes, Hotel Dieu -HME /ID# 219113
  • Savoie
    • Chambery, Savoie, France, 73000
      • Centre Hospitalier de CHAMBERY /ID# 224506
• Germany
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen /ID# 221522
  • Hamburg, Germany, 22081
    • OncoResearch Lerchenfeld GmbH /ID# 230867
  • Munich, Germany, 81675
    • Klinikum rechts der Isar - Technische Universitaet Muenchen /ID# 221520
  • Baden-Wuerttemberg
    • Mannheim, Baden-Wuerttemberg, Germany, 68167
      • Universitatsklinikum Mannheim /ID# 221523
  • Bayern
    • Muenchen, Bayern, Germany, 81241
      • Haemato-Onkologie /ID# 221061
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Universitaetsklinikum Aachen /ID# 221519
  • Sachsen
    • Dresden, Sachsen, 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
  • Attiki
    • Athens, Attiki, Greece, 11527
      • General Hospital of Athens Laiko /ID# 230785
    • Athens, Attiki, Greece, 12462
      • University General Hospital Attikon /ID# 230784
• Israel
  • Be'Er Ya'Akov, Israel, 70300
    • Assaf Harofeh Medical Center /ID# 222957
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 219120
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center /ID# 221374
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 219137
    • Tel Aviv-Yafo, Tel-Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 219134
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91120
      • Hadassah Medical Center-Hebrew University /ID# 219110
• Italy
  • Bergamo, Italy, 24127
    • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 221907
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 220867
  • Brescia, Italy, 25123
    • ASST Spedali civili di Brescia /ID# 241273
  • Catania, Italy, 95123
    • A.O.U. Policlinico G. Rodolico S.Marco- Presidio G.Rodolico /ID# 219085
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi /ID# 219086
  • Varese, Italy, 21100
    • ASST Sette Laghi /ID# 219084
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 219083
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 453-8511
      • Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital /ID# 239100
    • Toyoake-shi, Aichi, Japan, 470-1192
      • Fujita Health University Hospital /ID# 221537
  • Chiba
    • Chiba-shi, Chiba, Japan, 260-8677
      • 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-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 221783
  • Fukushima
    • Fukushima-shi, Fukushima, Japan, 960-1295
      • Fukushima Medical University Hospital /ID# 222752
  • Gifu
    • Ogaki-shi, Gifu, Japan, 503-8502
      • Ogaki Municipal Hospital /ID# 240173
  • Gunma
    • Maebashi-shi, Gunma, Japan, 371-0821
      • Gunmaken Saiseikai Maebashi Hospital /ID# 242806
    • Maebashi-shi, Gunma, Japan, 371-8511
      • Gunma University Hospital /ID# 221480
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital /ID# 242667
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 650-0017
      • Kobe University Hospital /ID# 246236
  • Ibaraki
    • Hitachi-shi, Ibaraki, Japan, 317-0077
      • Hitachi General Hospital /ID# 240048
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital /ID# 238424
  • Kagoshima
    • Kanoya-shi, Kagoshima, Japan, 893-0024
      • Medical Corporation Seijinkai Ikeda Hospital /ID# 242172
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 606-8507
      • Kyoto University Hospital /ID# 238423
  • Mie
    • Tsu-shi, Mie, Japan, 514-8507
      • Mie University Hospital /ID# 221664
  • Miyazaki
    • Miyazaki-shi, Miyazaki, Japan, 889-1692
      • University of Miyazaki Hospital /ID# 221483
  • Okayama
    • Kurashiki-shi, Okayama, Japan, 701-0192
      • Kawasaki Medical School Hospital /ID# 221481
    • Kurashiki-shi, Okayama, 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
      • Osaka University Hospital /ID# 221478
  • Saitama
    • Koshigaya-shi, Saitama, Japan, 343-8555
      • 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
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital /ID# 231667
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital /ID# 222087
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital /ID# 231666
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center /ID# 222089
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital /ID# 219055
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center /ID# 219054
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center /ID# 221068
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 219056
  • Gyeonggido
    • Seongnam, Gyeonggido, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital /ID# 219053
• 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
  • Zuid-Holland
    • Dordrecht, Zuid-Holland, Netherlands, 3318 AT
      • Albert Schweitzer Ziekenhuis /ID# 224015
• New Zealand
  • Auckland
    • Papatoetoe, Auckland, New Zealand, 2025
      • Middlemore Clinical Trials /ID# 230770
• Russian Federation
  • Petrozavodsk, Russian Federation, 185019
    • Republican hospital named after V.A. Baranov /ID# 221412
  • Saint Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinical Hospital /ID# 221028
  • Sankt-Peterburg, Russian Federation, 191024
    • Russian Research Institute of Hematology and Transfusiology of the FMBA /ID# 221029
  • Sankt-Peterburg, Russian Federation, 197341
    • Almazov National Medical Research Centre /ID# 221033
  • Tula, Russian Federation, 300053
    • Tula Regional Clinical Hospital /ID# 221027
  • Moskva
    • Moscow, Moskva, Russian Federation, 125284
      • Moscow State budget healthcare /ID# 221025
  • Stavropol Skiy Kray
    • Pyatigorsk, Stavropol Skiy Kray, Russian Federation, 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
      • Clinical Center Vojvodina /ID# 230853
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Wits Clinical Research Site /ID# 232071
    • Johannesburg, Gauteng, South Africa, 2193
      • Wits Clinical Research Site /ID# 232072
    • Pretoria, Gauteng, South Africa, 0044
      • Albert Alberts Stem Cell Transplant Centre /ID# 232073
• 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
  • Malaga, 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
      • 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
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 230720
• Sweden
  • Orebro Lan
    • Orebro, Orebro Lan, Sweden, 701 85
      • Orebro Universitetssjukhuset /ID# 220829
  • Skane Lan
    • Lund, Skane Lan, Sweden, SE 221 41
      • Skane University Hospital Lund /ID# 220835
  • Vastra Gotalands Lan
    • Gothenburg, Vastra Gotalands Lan, Sweden, 413 45
      • Sahlgrenska University Hospital /ID# 218776
• Taiwan
  • Taichung City, Taiwan, 40447
    • China Medical University Hospital /ID# 218978
  • Tainan City, Taiwan, 73657
    • Chi Mei Hospital - Liouying /ID# 221145
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital /ID# 218976
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 221146
  • Taoyuan City, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital /ID# 218983
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 833
      • Kaohsiung Chang Gung Memorial Hospital /ID# 218984
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe University Medical Faculty /ID# 230759
  • Edirne, Istanbul, Turkey, 22030
    • Trakya University Medical Facu /ID# 230754
  • Istanbul, Turkey, 34214
    • Bagcilar Medipol Mega Universite Hastanesi /ID# 230757
  • Izmir, Turkey, 35040
    • Ege University Medical Faculty /ID# 230753
  • Malatya, Turkey, 44280
    • Inonu University Medical Faculty /ID# 230758
• Ukraine
  • Kharkiv, Ukraine, 61070
    • Communal non-profit enterprise Regional Center of Oncology /ID# 230832
  • Kyiv, Ukraine, 02091
    • Medical Center "OK!Clinic+" /ID# 230834
  • Kyiv, Ukraine, 03143
    • Feofaniya Clinical Hospital of State Management of Affairs /ID# 232370
  • Lviv, Ukraine, 79044
    • SI Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine /ID# 230833
• 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
  • Lincolnshire
    • Lincoln, Lincolnshire, United Kingdom, LN2 4AX
      • United Lincolnshire Hospitals NHS Trust /ID# 231471
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 9RT
      • Guys and St Thomas NHS Foundation Trust /ID# 219185
  • 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 Medical Foundation /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, LLP- 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
    • Saint 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
      • 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
      • 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
      • University of Michigan Comprehensive Cancer Center Michigan Medicine /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 Thrombocytopenia [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
Experimental: Navitoclax + Ruxolitinib; Participants will receive Navitoclax in combination with Ruxolitinib	Drug: Ruxolitinib; Tablet; Oral; Drug: Navitoclax; Tablet; Oral; Other Names: ABT-263
Active Comparator: Placebo for Navitoclax + Ruxolitinib; Participants will receive placebo for Navitoclax and Ruxolitinib	Drug: Ruxolitinib; Tablet; Oral; Drug: Placebo for Navitoclax; Tablet; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Percentage of Participants who achieve Spleen Volume Reduction of at least 35% (SVR35)	Reduction in spleen volume is measured by MRI or CT, per IWG criteria.	Baseline (Week 0) Up to Week 96
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).	Baseline (Week 0) Up to Week 96
Change In Fatigue	Change in fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue SF 7a.	Baseline (Week 0) Up to Week 24
Percentage of Participants who achieve Anemia Response	The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.	Baseline (Week 0) Up to Week 96
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death from any cause.	Up To approximately 8 Years
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 approximately 8 Years
Change 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
Change in Physical Functioning	Change in 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 24
Percentage of Participants who Achieve Reduction in Grade of Bone Marrow Fibrosis	Change in grade of bone marrow fibrosis will be measured per the European consensus grading system through bone marrow biopsy.	Baseline (Week 0) Up to Week 96

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 (Estimated): October 19, 2032

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 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Ruxolitinib; Myelofibrosis; Navitoclax; ABT-263; TRANSFORM-1
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis; Antineoplastic Agents; 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 data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on 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