A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis
REFINE
A Phase 2 Open-Label Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Subjects With Myelofibrosis (REFINE)
2 other identifiers
interventional
191
14 countries
91
Brief Summary
This is a Phase 2 open-label, multicenter study evaluating tolerability and efficacy of navitoclax alone or when added to ruxolitinib in participants with myelofibrosis.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2017
Longer than P75 for phase_2
91 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 17, 2017
CompletedFirst Posted
Study publicly available on registry
July 19, 2017
CompletedStudy Start
First participant enrolled
October 31, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 28, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
January 29, 2025
CompletedResults Posted
Study results publicly available
March 12, 2025
CompletedJanuary 20, 2026
December 1, 2025
4.4 years
July 17, 2017
February 24, 2025
December 29, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume at Week 24
Reduction in spleen volume is measured by magnetic resonance imaging/computerized tomography (MRI/CT).
Baseline, Week 24
Secondary Outcomes (4)
Percentage of Participants Achieving ≥ 50% Reduction From Baseline in Total System Score (TSS) at Week 24
Baseline, Week 24
Percentage of Participants Achieving Anemia Response
Up to 254 weeks
Percentage of Participants With ≥ 1 Grade Reduction From Baseline in Fibrosis Grade At Any Time
Up to 254 weeks
Time to First Reduction in Fibrosis Grade
Up to 254 weeks
Study Arms (4)
Navitoclax + ruxolitinib (Cohort 1a)
EXPERIMENTALParticipants must have received ruxolitinib for at least 12 weeks and on stable dose of ≥10 mg tablets orally twice daily (BID) for ≥8 weeks prior to the 1st dose of navitoclax. Navitoclax tablets are administered once daily (QD) at a starting dose of 50 mg. This was increased after approximately ≥7 days to next dose level if platelet count is ≥75 × 10\^9/L up to a maximum dose of navitoclax 300 mg QD. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first).
Navitoclax + ruxolitinib (Cohort 1b)
EXPERIMENTALThose receiving ruxolitinib at Screening must be on a stable dose ≥10 mg tablets orally twice daily (BID) for ≥ 4 weeks prior to 1st dose of navitoclax. Those not receiving ruxolitinib at Screening received 10 mg ruxolitinib BID starting on Day 1. 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 24 disease assessment, navitoclax dose was increased to 300 mg QD at discretion of the Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first).
Navitoclax (Cohort 2)
EXPERIMENTALParticipants must have received prior treatment with a Janus Kinase 2 (JAK-2) inhibitor. Those with Baseline platelet count \>150 × 10\^9/L initiated navitoclax film-coated tablets orally once daily (QD) at the starting dose of 200 mg. Those with a Baseline platelet count ≤150 × 10\^9/L initiated navitoclax film-coated tablets orally once daily (QD) at the starting dose of 100 mg, which could be increased to 200 mg once daily after 7 days provided the platelet count is ≥75 × 10\^9/L. Navitoclax didn't exceed 200 mg QD for the first 24 weeks of treatment. After Week 24 disease assessment, navitoclax dose may be increased to 300 mg QD at discretion of the Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first).
Navitoclax + ruxolitinib (Cohort 3)
EXPERIMENTALPrior treatment with a Janus Kinase 2 (JAK-2) or Bromodomain and Extra-Terminal motif (BET) proteins inhibitor was prohibited. Ruxolitinib tablets administered orally twice daily (BID) based on Baseline platelet count as per the local approved label. 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 24 disease assessment, navitoclax dose may be increased to 300 mg QD at discretion of Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first).
Interventions
Tablet; Oral
Film-coated tablet; Oral
Eligibility Criteria
You may qualify if:
- Participants with documented diagnosis of intermediate-2 or high-risk primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis.
- Participant must be ineligible due to age, comorbidities, or unfit for unrelated or unmatched donor transplantation or unwilling to undergo stem cell transplantation at time of study entry.
- Eastern Cooperative Oncology Group (ECOG) of 0, 1, or 2.
- Prior treatment must meet at least one of the following criteria:
- Prior or current treatment with ruxolitinib and no prior treatment with a Bromodomain and Extra-Terminal motif (BET) proteins inhibitor or another Janus Kinase 2 (JAK-2) inhibitor, and meet all of the following criteria:
- Ruxolitinib treatment must meet at least one of the following criteria:
- Ruxolitinib treatment for \>=24 weeks with lack of efficacy defined as a lack of spleen response (refractory) or a loss of spleen or symptom response (relapsed)
- Ruxolitinib treatment for \<24 weeks with documented disease progression on spleen measurements while on ruxolitinib as defined in the protocol:
- Ruxolitinib treatment for \>=28 days with intolerance defined as new red blood cell 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.
- If receiving ruxolitinib at the time of screening, must currently be on a stable dose \>=10 mg twice daily of ruxolitinib for \>=4 weeks prior to the 1st dose of navitoclax.
- Participant has at least 2 symptoms each with a score \>=3 or a total score of \>=12, as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days during screening prior to study drug dosing; OR
- Prior treatment with a JAK-2 inhibitor and meet one of the following criteria:
- Prior treatment with a JAK-2 inhibitor for at least 12 weeks
- Prior treatment with a JAK-2 inhibitor for \>=28 days complicated by either development of red blood cell transfusion requirement (at least 2 units/month for 2 months) OR Grade \>= 3 adverse events of thrombocytopenia, anemia, hematoma and/or hemorrhage while on JAK-2 inhibitor treatment; OR
- No prior treatment with a JAK-2 or BET inhibitor.
- +2 more criteria
You may not qualify if:
- Splenic irradiation within 6 months prior to screening, or prior splenectomy.
- Leukemic transformation (\> 10% blasts in peripheral blood or bone marrow aspirate/biopsy).
- Participant is currently on medications that interfere with coagulation (including warfarin) or platelet function within 3 days prior to the first dose of study drug or during the study treatment period with the exception of low dose aspirin (up to 100 mg/day) and low-molecular-weight heparin.
- Prior therapy with a BH3 mimetic compound or stem cell transplantation.
- Participant has received strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) or moderate CYP3A inhibitors (e.g., fluconazole) within 14 days prior to the administration of the first dose of study drug.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AbbVielead
Study Sites (91)
UAB Comprehensive Cancer Cente /ID# 165464
Birmingham, Alabama, 35217, United States
TOI Clinical Research /ID# 222546
Cerritos, California, 90703-2679, United States
City of Hope /ID# 221395
Duarte, California, 91010, United States
Moores Cancer Center at UC San Diego /ID# 164084
La Jolla, California, 92093, United States
Long Beach Memorial Medical Ct /ID# 230148
Long Beach, California, 90806-1701, United States
University of Southern California /ID# 164095
Los Angeles, California, 90033, United States
Colorado Blood Cancer Institute /ID# 224250
Denver, Colorado, 80218, United States
Baptist MD Anderson Cancer Center - Jacksonville /ID# 222548
Jacksonville, Florida, 32207-8432, United States
Mayo Clinic /ID# 164201
Jacksonville, Florida, 32224, United States
Moffitt Cancer Center /ID# 164082
Tampa, Florida, 33612-9416, United States
University of Chicago Medicine /ID# 164115
Chicago, Illinois, 60637-1426, United States
Mid Illinois Hematology & Oncology Associates, Ltd /ID# 230536
Normal, Illinois, 61761, United States
Indiana Blood & Marrow Transpl /ID# 165075
Indianapolis, Indiana, 46237, United States
Duplicate_American Oncology Partners of Maryland, PA /ID# 231299
Bethesda, Maryland, 20817, United States
Dana-Farber Cancer Institute /ID# 162675
Boston, Massachusetts, 02215, United States
University of Massachusetts - Worcester /ID# 222547
Worcester, Massachusetts, 01655, United States
Henry Ford Hospital /ID# 162682
Detroit, Michigan, 48202, United States
Ascension Providence Southfield Cancer Center /ID# 223876
Southfield, Michigan, 48075-3707, United States
MidAmerica Division, Inc. /ID# 222058
Kansas City, Missouri, 64132, United States
Weill Cornell Medical College /ID# 162679
New York, New York, 10065, United States
The Ohio State University /ID# 217402
Columbus, Ohio, 43210-1280, United States
Bend Memorial Clinic /ID# 224184
Bend, Oregon, 97701, United States
West Penn Hospital /ID# 222618
Pittsburgh, Pennsylvania, 15224-1722, United States
Duplicate_Medical University of South Carolina /ID# 222597
Charleston, South Carolina, 29425, United States
Prairie Lakes Healthcare System /ID# 224358
Watertown, South Dakota, 57201, United States
Tennessee Oncology-Nashville Centennial /ID# 221410
Nashville, Tennessee, 37203-1632, United States
Texas Oncology - West Texas /ID# 224784
Abilene, Texas, 79606, United States
Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 225159
Dallas, Texas, 75246-2003, United States
Oncology Consultants /ID# 230930
Houston, Texas, 77030-3306, United States
MD Anderson Cancer Center at Texas Medical Center /ID# 162683
Houston, Texas, 77030-4000, United States
University of Texas Health San Antonio MD Anderson Cancer Center /ID# 164094
San Antonio, Texas, 78229, United States
Utah Cancer Specialists Salt Lake Clinic /ID# 222806
Salt Lake City, Utah, 84106, United States
University of Utah /ID# 164116
Salt Lake City, Utah, 84112-5500, United States
The Kinghorn Cancer Centre /ID# 214657
Darlinghurst, New South Wales, 2010, Australia
Barwon Health /ID# 222430
Geelong, Victoria, 3220, Australia
Peter MacCallum Cancer Ctr /ID# 218352
Melbourne, Victoria, 3000, Australia
The Alfred Hospital /ID# 215545
Melbourne, Victoria, 3004, Australia
Fiona Stanley Hospital /ID# 216809
Murdoch, Western Australia, 6150, Australia
Duplicate_University of Alberta Hospital - Division of Hematology /ID# 217698
Edmonton, Alberta, T6G 2B7, Canada
University Health Network_Princess Margaret Cancer Centre /ID# 214483
Toronto, Ontario, M5G 2M9, Canada
McGill University Health Center Research Institute /ID# 223976
Montreal, Quebec, H4A 3J1, Canada
Clinical Hospital Dubrava /ID# 230504
Zagreb, City of Zagreb, 10000, Croatia
Klinicka bolnica Merkur /ID# 230599
Zagreb, City of Zagreb, 10000, Croatia
Klinicki bolnicki centar Zagreb /ID# 230602
Zagreb, City of Zagreb, 10000, Croatia
Klinicki Bolnicki Centar (KBC) Split /ID# 230601
Split, Split-Dalmatia County, 21000, Croatia
General Hospital of Athens Laiko /ID# 230394
Athens, Attica, 11527, Greece
Duplicate_University General Hospital Attikon /ID# 230395
Athens, Attica, 12462, Greece
Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz /ID# 230585
Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary
Semmelweis Egyetem /ID# 230518
Budapest, 1085, Hungary
Duplicate_Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 230306
Budapest, 1097, Hungary
Hadassah Medical Center-Hebrew University /ID# 230310
Jerusalem, Jerusalem, 91120, Israel
Galilee Medical Center /ID# 230397
Nahariya, Northern District, 2210001, Israel
Assuta Ashdod Medical Center /ID# 230396
Ashdod, Southern District, 7747629, Israel
Tel Aviv Sourasky Medical Center /ID# 230311
Tel Aviv, Tel Aviv, 6423906, Israel
IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 230012
Bologna, Emilia-Romagna, 40138, Italy
Azienda Ospedaliero Universitaria Careggi /ID# 214555
Florence, Firenze, 50134, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 214553
Rome, Roma, 00168, Italy
ASST Papa Giovanni XXIII /ID# 214900
Bergamo, 24127, Italy
ASST degli Spedali Civili di Brescia /ID# 230420
Brescia, 25123, Italy
AOU Policlinico G. Rodolico - San Marco /ID# 214549
Catania, 95123, Italy
Grande Ospedale Metropolitano Bianchi - Melacrino - Morelli P.O. Riuniti /ID# 230011
Reggio Calabria, 89125, Italy
ASST Sette Laghi - Ospedale Di Circolo E Fondazione Macchi Varese /ID# 214551
Varese, 21100, Italy
Fujita Health University Hospital /ID# 221539
Toyoake, Aichi-ken, 470-1192, Japan
Aomori Prefectural Central Hospital /ID# 221773
Aomori, Aomori, 030-8553, Japan
Kyushu University Hospital /ID# 222691
Fukuoka, Fukuoka, 812-8582, Japan
Sapporo Hokuyu Hospital /ID# 222693
Sapporo, Hokkaido, 003-0006, Japan
Kansai Medical University Hospital /ID# 222690
Hirakata-shi, Osaka, 573-1191, Japan
Kindai University Hospital /ID# 222689
Osakasayama-shi, Osaka, 589-8511, Japan
Duplicate_Dokkyo Medical University Saitama Medical Center /ID# 222332
Koshigaya-shi, Saitama, 343-8555, Japan
Juntendo University Hospital /ID# 221484
Bunkyo-ku, Tokyo, 113-8431, Japan
Nippon Medical School Hospital /ID# 222692
Bunkyo-ku, Tokyo, 113-8602, Japan
University of Yamanashi Hospital /ID# 221700
Chuo-shi, Yamanashi, 409-3821, Japan
VA Caribbean Healthcare System /ID# 222416
San Juan, 00921-3201, Puerto Rico
Hospital del Centro Comprensivo de Cancer de la UPR /ID# 222544
San Juan, 00927, Puerto Rico
Seoul National University Hospital /ID# 230380
Seoul, Seoul Teugbyeolsi, 03080, South Korea
Samsung Medical Center /ID# 230381
Seoul, Seoul Teugbyeolsi, 06351, South Korea
Hospital Universitario Germans Trias i Pujol /ID# 214704
Badalona, Barcelona, 08916, Spain
Duplicate_CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 230718
Pamplona, Navarre, 31008, Spain
Hospital Universitario Vall d'Hebron /ID# 222415
Barcelona, 08035, Spain
Hospital General Universitario Gregorio Maranon /ID# 214676
Madrid, 28007, Spain
CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 230719
Madrid, 28027, Spain
Hospital Universitario 12 de Octubre /ID# 214710
Madrid, 28041, Spain
Hospital Universitario Virgen de la Victoria /ID# 214709
Málaga, 29010, Spain
Hospital Regional Universitario de Malaga /ID# 230858
Málaga, 29011, Spain
Kaohsiung Chang Gung Memorial Hospital /ID# 230371
Kaohsiung City, Kaohsiung, 833, Taiwan
National Cheng Kung University Hospital /ID# 230372
Tainan, 704, Taiwan
Guys and St Thomas NHS Foundation Trust /ID# 164110
London, Greater London, SE1 9RT, United Kingdom
Oxford University Hospitals NHS Foundation Trust /ID# 214503
Oxford, Oxfordshire, OX3 9DU, United Kingdom
Belfast Health and Social Care Trust /ID# 216991
Belfast, BT9 7AB, United Kingdom
The Christie Hospital /ID# 164111
Manchester, M20 4BX, United Kingdom
Aneurin Bevan University Health Board /ID# 230332
Newport, NP18 3XQ, United Kingdom
Related Publications (4)
Passamonti F, Foran JM, Tandra A, De Stefano V, Fox ML, Mattour A, McMullin MF, Perkins AC, Rodriguez-Macias G, Sibai HA, Polepally AR, Sun Y, Chopra AS, Harb JG, Qin Q, Potluri J, How J. Preliminary Safety and Efficacy of Navitoclax Plus Ruxolitinib in Janus Kinase Inhibitor-Naive Patients With Myelofibrosis From the Multicenter, Open-Label, Phase 2 Study (REFINE). Hematol Oncol. 2026 Mar;44(2):e70180. doi: 10.1002/hon.70180.
PMID: 41846295DERIVEDPemmaraju N, Somervaille TCP, Palandri F, Harrison C, Komrokji RS, Perkins A, Ayala Diaz RM, Lavie D, Tomita A, Feng Y, Qin Q, Harb J, Polepally AR, Potluri J, Garcia JS. Addition of navitoclax to ruxolitinib for patients with myelofibrosis with progression or suboptimal response. Blood Neoplasia. 2024 Nov 2;2(1):100056. doi: 10.1016/j.bneo.2024.100056. eCollection 2025 Feb.
PMID: 40454409DERIVEDPemmaraju N, Garcia JS, Potluri J, Harb JG, Sun Y, Jung P, Qin QQ, Tantravahi SK, Verstovsek S, Harrison C. Addition of navitoclax to ongoing ruxolitinib treatment in patients with myelofibrosis (REFINE): a post-hoc analysis of molecular biomarkers in a phase 2 study. Lancet Haematol. 2022 Jun;9(6):e434-e444. doi: 10.1016/S2352-3026(22)00116-8. Epub 2022 May 13.
PMID: 35576960DERIVEDHarrison CN, Garcia JS, Somervaille TCP, Foran JM, Verstovsek S, Jamieson C, Mesa R, Ritchie EK, Tantravahi SK, Vachhani P, O'Connell CL, Komrokji RS, Harb J, Hutti JE, Holes L, Masud AA, Nuthalapati S, Potluri J, Pemmaraju N. Addition of Navitoclax to Ongoing Ruxolitinib Therapy for Patients With Myelofibrosis With Progression or Suboptimal Response: Phase II Safety and Efficacy. J Clin Oncol. 2022 May 20;40(15):1671-1680. doi: 10.1200/JCO.21.02188. Epub 2022 Feb 18.
PMID: 35180010DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Medical Services
- Organization
- AbbVie
Study Officials
- STUDY DIRECTOR
ABBVIE INC.
AbbVie
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
July 17, 2017
First Posted
July 19, 2017
Study Start
October 31, 2017
Primary Completion
March 28, 2022
Study Completion
January 29, 2025
Last Updated
January 20, 2026
Results First Posted
March 12, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
- 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/
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.