Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis (TRANSFORM-2)
Myelofibrosis (MF)
About this trial
This is an interventional treatment trial for Myelofibrosis (MF) focused on measuring ABT-263, Navitoclax, Ruxolitinib, MF, Myelofibrosis, Cancer
Eligibility Criteria
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 BH3-mimetic compound, bromodomain and extra-terminal (BET) inhibitor, or 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).
Sites / Locations
- Ironwood Cancer & Res Ctr /ID# 222162Recruiting
- Highlands Oncology Group, PA /ID# 221826Recruiting
- Moores Cancer Center at UC San Diego /ID# 219009Recruiting
- Long Beach Memorial Medical Ct /ID# 224542Recruiting
- Icri /Id# 221967Recruiting
- St. Mary's Hospital Regional Cancer Center /ID# 224229Recruiting
- Augusta University Georgia Cancer Center /ID# 219051Recruiting
- Columbus Regional Research Institute /ID# 224410Recruiting
- Northwest Oncology & Hematology - Elk Grove Village /ID# 222818Recruiting
- Loyola University Medical Ctr /ID# 219048Recruiting
- Indiana Blood & Marrow Transpl /ID# 221587Recruiting
- Tulane Medical Center - New Orleans /ID# 222940
- Ochsner Clinic Foundation-New Orleans /ID# 222777Recruiting
- American Oncology Partners of Maryland, PA /ID# 222836Recruiting
- Dana-Farber Cancer Institute /ID# 218998Recruiting
- University of Michigan /ID# 218463Recruiting
- Henry Ford Health System /ID# 221190Recruiting
- William Beaumont Hospital /ID# 222705Recruiting
- Saint Louis University Cancer Center /ID# 222287Recruiting
- Summit Medical Group-Florham Park /ID# 222620Recruiting
- Hackensack Univ Med Ctr /ID# 219047Recruiting
- The Cancer Institute at St. Francis Hospital /ID# 231782Recruiting
- Manhattan Hematology Oncology MHO Associates /ID# 223193Recruiting
- Memorial Sloan Kettering Cancer Center-Koch Center /ID# 221081Recruiting
- Wake Forest Baptist Medical Center /ID# 222899Recruiting
- MetroHealth Medical Center /ID# 222650Recruiting
- Hospital of the University of Pennsylvania /ID# 219001Recruiting
- Fox Chase Cancer Center /ID# 223955Recruiting
- Houston Methodist Hospital /ID# 223103
- University of Texas Health San Antonio MD Anderson Cancer Center /ID# 233942
- Utah Cancer Specialists Salt Lake Clinic /ID# 221962Recruiting
- Virginia Cancer Specialists - Fairfax /ID# 223016Recruiting
- Providence Everett /ID# 223130
- Yakima Valley Memorial Hosp /ID# 224368Recruiting
- HSHS St. Vincent Hospital /ID# 224468Recruiting
- The Kinghorn Cancer Centre /ID# 221097Recruiting
- Border Medical Oncology Research Unit Albury Wodonga Regional Cancer Centre /ID# 223848Recruiting
- Calvary Mater Newcastle /ID# 224324Recruiting
- Alfred Health /ID# 221096Recruiting
- Royal Perth Hospital /ID# 221099Recruiting
- Universitaetsklinikum St. Poelten /ID# 221709Recruiting
- Ordensklinikum Linz GmbH Elisabethinen /ID# 220914Recruiting
- Klinikum Wels-Grieskirchen GmbH /ID# 220915Recruiting
- Medizinische Universitaet Graz /ID# 220919Recruiting
- Medizinische Universitaet Wien /ID# 220911Recruiting
- Hanusch Krankenhaus /ID# 220912Recruiting
- ZNA Cadix /ID# 221468Recruiting
- UCL Saint-Luc /ID# 224221Recruiting
- Grand Hopital de Charleroi /ID# 224827Recruiting
- UZ Gent /ID# 220841Recruiting
- AZ-Delta /ID# 221469Recruiting
- Vitaz /Id# 228150Recruiting
- UMHAT Alexandrovska EAD /ID# 231652Recruiting
- UMHAT Dr Georgi Stranski EAD /ID# 231650Recruiting
- Acibadem City Clinic Tokuda University Hospital EAD /ID# 231649Recruiting
- UMHAT Sveti Ivan Rilski /ID# 231651Recruiting
- UMHAT Sveta Marina /ID# 234119Recruiting
- Juravinski Cancer Centre /ID# 220887Recruiting
- Ottawa Hospital Research Institute /ID# 238858Recruiting
- CISSS-CA (Centre Integre de sante et de services sociaux de Chaudiere-Appalache) /ID# 222433Recruiting
- McGill University Health Center Research Institute /ID# 222614Recruiting
- Clinical Hospital Dubrava /ID# 230801Recruiting
- Klinicka bolnica Merkur /ID# 230799Recruiting
- Klinicki bolnicki centar Zagreb /ID# 230798
- Klinicki bolnicki centar Osijek /ID# 231503Recruiting
- Klinicki bolnicki centar Split /ID# 230800Recruiting
- Fakultni Nemocnice Brno /ID# 220959Recruiting
- Vseobecna fakultni nemocnice v Praze /ID# 220969
- Aalborg University Hospital /ID# 224391Recruiting
- Sjællands Universitetshospital /ID# 224456Recruiting
- HCL - Hopital Lyon Sud /ID# 222695Recruiting
- CHU NIMES - Hopital Caremeau /ID# 219128Recruiting
- CHU Bordeaux - Hopital Haut Leveque /ID# 222696Recruiting
- Hopital Avicenne - APHP /ID# 221287
- CHU de Nantes, Hotel Dieu -HME /ID# 219127Recruiting
- Centre Hospitalier de CHAMBERY /ID# 223771Recruiting
- Chu Angers /Id# 219129Recruiting
- AP-HP - Hopital Saint-Louis /ID# 221390Recruiting
- Universitatsklinikum Mannheim /ID# 221529Recruiting
- Stauferklinikum Schwaebisch Gmuend /ID# 223948Recruiting
- Haematologisch-Onkologische Praxis im Zentrum Augsburg /ID# 225025
- BAG Freiberg-Richter, Jacobasch, Illmer, Wolf /ID# 221346Recruiting
- Augusta-Kranken-Anstalt gGmbH, Bochum-Mitte /ID# 224695
- Klinikum Chemnitz gGmbH /ID# 224575Recruiting
- OncoResearch Lerchenfeld GmbH /ID# 225034Recruiting
- Klinikum rechts der Isar - Technische Universitaet Muenchen /ID# 221526Recruiting
- Universitaetsmedizin Rostock /ID# 224157Recruiting
- General Hospital of Athens Laiko /ID# 221175Recruiting
- General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 221179Recruiting
- University General Hospital of Patras /ID# 221178Recruiting
- General Hospital of Thessaloniki George Papanikolaou /ID# 221463Recruiting
- Szegedi Tudomanyegyetem /ID# 220955Recruiting
- Fejer Megyei Szent Gyorgy Korhaz /ID# 220949Recruiting
- Debreceni Egyetem Klinikai Kozpont /ID# 220947Recruiting
- Somogy Varmegyei Kaposi Mor Oktato Korhaz /ID# 220948
- Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz /ID# 220946Recruiting
- The Chaim Sheba Medical Center /ID# 219136Recruiting
- Tel Aviv Sourasky Medical Center /ID# 219135Recruiting
- Hadassah Medical Center-Hebrew University /ID# 219111Recruiting
- HaEmek Medical Center /ID# 220839Recruiting
- Assuta Ashdod Medical Center /ID# 225281Recruiting
- Assaf Harofeh Medical Center /ID# 222972Recruiting
- Rambam Health Care Campus /ID# 219121
- The Lady Davis Carmel Medical Center /ID# 222973Recruiting
- Hadassah Mt. Scopus /ID# 253394Recruiting
- Galilee Medical Center /ID# 225280Recruiting
- Rabin Medical Center /ID# 219139Recruiting
- Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 225731Recruiting
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 219087Recruiting
- ASST Monza/Ospedale San Gerardo /ID# 225113Recruiting
- Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 238438Recruiting
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 221222Recruiting
- IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 221077Recruiting
- A.O.U. Policlinico G. Rodolico S.Marco- Presidio G.Rodolico /ID# 219089Recruiting
- Azienda Ospedaliero Universitaria Careggi /ID# 219090Recruiting
- Azienda Ospedaliera Universitaria Federico II /ID# 224673Recruiting
- Azienda Ospedaliera Universitaria Paolo Giaccone /ID# 221078Recruiting
- Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 221220Recruiting
- A.O.U. Citta della Salute e della Scienza di Torino /ID# 221223Recruiting
- Azienda Ospedaliera Universitaria Friuli Centrale/Presidio Ospedaliero Universit /ID# 221241Recruiting
- ASST Sette Laghi /ID# 234183Recruiting
- Azienda ULSS 8 Berica/Ospedale San Bortolo di Vicenza /ID# 221079Recruiting
- Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital /ID# 221150Recruiting
- Fujita Health University Hospital /ID# 221598Recruiting
- Chiba University Hospital /ID# 224546Recruiting
- National Cancer Center Hospital East /ID# 226653Recruiting
- Ehime University Hospital /ID# 221158Recruiting
- Kyushu University Hospital /ID# 221606Recruiting
- Fukushima Medical University Hospital /ID# 221877Recruiting
- Gifu University Hospital /ID# 224371Recruiting
- Sapporo Hokuyu Hospital /ID# 221149Recruiting
- Kobe City Medical Center General Hospital /ID# 221156Recruiting
- Kanazawa University Hospital /ID# 223028Recruiting
- Iwate Medical University Hospital /ID# 222044Recruiting
- Shonan Kamakura General Hospital /ID# 223030Recruiting
- Kumamoto Shinto General Hospital /ID# 255645Recruiting
- Kyoto University Hospital /ID# 223008Recruiting
- Mie University Hospital /ID# 221665Recruiting
- University of Miyazaki Hospital /ID# 221821Recruiting
- Niigata University Medical & Dental Hospital /ID# 223034Recruiting
- Kurashiki Central Hospital /ID# 221690Recruiting
- Kansai Medical University Hospital /ID# 257289Recruiting
- Osaka University Hospital /ID# 221159Recruiting
- Dokkyo Medical University Saitama Medical Center /ID# 222334Recruiting
- Juntendo University Shizuoka Hospital /ID# 221780Recruiting
- Juntendo University Hospital /ID# 221154Recruiting
- Nippon Medical School Hospital /ID# 221676Recruiting
- The Institute of Medical Science the University of Tokyo Hospital /ID# 257944Recruiting
- Tokyo Medical University Hospital /ID# 221540Recruiting
- Tokyo Metropolitan Bokutoh Hospital /ID# 254774Recruiting
- University of Yamanashi Hospital /ID# 221706Recruiting
- Pusan National University Hospital /ID# 220980Recruiting
- Gachon University Gil Medical Center /ID# 220972Recruiting
- Seoul National University Hospital /ID# 219060Recruiting
- Samsung Medical Center /ID# 221091Recruiting
- The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 219061Recruiting
- Aotearoa Clinical Trials /ID# 232201Recruiting
- Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopern /ID# 221161Recruiting
- Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie /ID# 221124Recruiting
- SP ZOZ Szpital Uniwersytecki w Krakowie /ID# 221160
- LUX MED Onkologia - Szpital Szamocka /ID# 221265
- Uniwersyteckie Centrum Kliniczne /ID# 221298Recruiting
- ARS-MEDICAL Sp. z o.o. /ID# 238336Recruiting
- Pratia Onkologia Katowice /ID# 224526
- Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola /ID# 241031Recruiting
- MTZ Clinical Research Powered by Pratia /ID# 221759Recruiting
- Hospital del Centro Comprensivo de Cancer de la UPR /ID# 223281Recruiting
- Moscow State budget healthcare /ID# 221116
- Hospital n.a. V.V. Veresaev /ID# 225221
- Russian Research Institute of Hematology and Transfusiology of the FMBA /ID# 221115
- Almazov National Medical Research Centre /ID# 221114
- Tula Regional Clinical Hospital /ID# 221302
- University Clinical Center Serbia /ID# 231058Recruiting
- Clin Hosp Ctr Bezanijska Kosa /ID# 231059Recruiting
- Clinical Center Vojvodina /ID# 231057Recruiting
- Wits Clinical Research Site /ID# 231554Recruiting
- Alberts Cellular Therapy /ID# 231556Recruiting
- Hospital Clínico Universitario de Santiago-CHUS /ID# 221616Recruiting
- Hospital Universitario Central de Asturias /ID# 224815Recruiting
- Hospital Universitario Germans Trias i Pujol /ID# 233727Recruiting
- Hospital Universitario Dr. Negrin /ID# 220923Recruiting
- Hospital Universitario A Coruna - CHUAC /ID# 224617Recruiting
- Hospital Parc de Salut del Mar /ID# 220922Recruiting
- Hospital Universitario Vall d'Hebron /ID# 240979Recruiting
- Hospital Universitario Virgen de las Nieves /ID# 253936Recruiting
- Hospital Universitario 12 de Octubre /ID# 233726Recruiting
- Hospital Universitario La Paz /ID# 224813Recruiting
- Hospital Regional Universitario de Malaga /ID# 221906
- Hospital Universitario de Salamanca /ID# 221904
- Hospital Universitario Virgen del Rocio /ID# 221932Recruiting
- Hospital Clinico Universitario de Valencia /ID# 220920Recruiting
- Skane University Hospital Lund /ID# 220834Recruiting
- Universitätsspital Basel /ID# 221261
- Inselspital, Universitätsspital Bern /ID# 223439
- Kaohsiung Chang Gung Memorial Hospital /ID# 218985Recruiting
- Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 218980Recruiting
- China Medical University Hospital /ID# 218979Recruiting
- Chi Mei Hospital - Liouying /ID# 221144Recruiting
- Taipei Veterans General Hosp /ID# 221147Recruiting
- Linkou Chang Gung Memorial Hospital /ID# 218982Recruiting
- Gulhane Askeri Tip Academy /ID# 224568Recruiting
- Trakya University Medical Facu /ID# 224572Recruiting
- Ege University Medical Faculty /ID# 224570Recruiting
- Mersin University Medical /ID# 224571Recruiting
- Ondokuz mayis University Facul /ID# 224567Recruiting
- United Lincolnshire Hospitals NHS Trust /ID# 224613Recruiting
- Guys and St Thomas NHS Foundation Trust /ID# 221041Recruiting
- James Paget University Hospitals NHS Foundation Trust /ID# 221219Recruiting
- University Hospitals Birmingham NHS Foundation Trust /ID# 221334Recruiting
- NHS Lothian /ID# 224378Recruiting
- The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 221335Recruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm A: Navitoclax + Ruxolitinib
Arm B: Best Available Therapy (BAT)
Participants will receive navitoclax tablets once daily and ruxolitinib tablets twice daily.
Participants will receive one of the BAT options, per the investigator's discretion.