A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis

Myelofibrosis (MF) Clinical Trial

— REFINE  

Official title:

A Phase 2 Open-Label Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Subjects With Myelofibrosis (REFINE)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03222609
• Other study ID #: M16-109
• Secondary ID: 2017-001398-17
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 31, 2017
• Est. completion date: February 2, 2029

Study information

• Verified date: June 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 191
• Est. completion date: February 2, 2029
• Est. primary completion date: March 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• Participant has splenomegaly as defined in the protocol.

• Participant must meet the laboratory parameters (adequate bone marrow, renal and hepatic function) as defined in the protocol.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Myelofibrosis (MF)
• Primary Myelofibrosis

Intervention

Drug:
• Ruxolitinib
Tablet; Oral
• Navitoclax
Tablet; Oral

Locations

Country	Name	City	State
Australia	The Kinghorn Cancer Centre /ID# 214657	Darlinghurst	New South Wales
Australia	Barwon Health /ID# 222430	Geelong	Victoria
Australia	Alfred Health /ID# 215545	Melbourne	Victoria
Australia	Peter MacCallum Cancer Ctr /ID# 218352	Melbourne	Victoria
Australia	Fiona Stanley Hospital /ID# 216809	Murdoch	Western Australia
Canada	University of Alberta Hospital - Division of Hematology /ID# 217698	Edmonton	Alberta
Canada	McGill University Health Center Research Institute /ID# 223976	Montreal	Quebec
Canada	Princess Margaret Cancer Centre /ID# 214483	Toronto	Ontario
Croatia	Klinicki bolnicki centar Split /ID# 230601	Split	Splitsko-dalmatinska Zupanija
Croatia	Clinical Hospital Dubrava /ID# 230504	Zagreb	Grad Zagreb
Croatia	Klinicka bolnica Merkur /ID# 230599	Zagreb	Grad Zagreb
Croatia	Klinicki bolnicki centar Zagreb /ID# 230602	Zagreb	Grad Zagreb
Greece	General Hospital of Athens Laiko /ID# 230394	Athens	Attiki
Greece	University General Hospital Attikon /ID# 230395	Athens	Attiki
Hungary	Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 230306	Budapest
Hungary	Semmelweis Egyetem /ID# 230518	Budapest
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Josa Andras Okta /ID# 230585	Nyiregyhaza	Szabolcs-Szatmar-Bereg
Israel	Assuta Ashdod Medical Center /ID# 230396	Ashdod
Israel	Hadassah Medical Center-Hebrew University /ID# 230310	Jerusalem	Yerushalayim
Israel	Galilee Medical Center /ID# 230397	Nahariya
Israel	Tel Aviv Sourasky Medical Center /ID# 230311	Tel Aviv-Yafo	Tel-Aviv
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 214900	Bergamo
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 230012	Bologna
Italy	ASST Spedali civili di Brescia /ID# 230420	Brescia
Italy	A.O.U. Policlinico G. Rodolico S.Marco- Presidio G.Rodolico /ID# 214549	Catania
Italy	Azienda Ospedaliero Universitaria Careggi /ID# 214555	Florence
Italy	Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 230011	Reggio Calabria
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 214553	Rome	Lazio
Italy	ASST Sette Laghi /ID# 214551	Varese
Japan	Aomori Prefectural Central Hospital /ID# 221773	Aomori-shi	Aomori
Japan	Juntendo University Hospital /ID# 221484	Bunkyo-ku	Tokyo
Japan	Nippon Medical School Hospital /ID# 222692	Bunkyo-ku	Tokyo
Japan	University of Yamanashi Hospital /ID# 221700	Chuo-shi	Yamanashi
Japan	Kyushu University Hospital /ID# 222691	Fukuoka-shi	Fukuoka
Japan	Kansai Medical University Hospital /ID# 222690	Hirakata-shi	Osaka
Japan	Dokkyo Medical University Saitama Medical Center /ID# 222332	Koshigaya-shi	Saitama
Japan	Kindai University Hospital /ID# 222689	Osakasayama-shi	Osaka
Japan	Sapporo Hokuyu Hospital /ID# 222693	Sapporo-shi	Hokkaido
Japan	Fujita Health University Hospital /ID# 221539	Toyoake-shi	Aichi
Korea, Republic of	Samsung Medical Center /ID# 230381	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 230380	Seoul
Puerto Rico	Hospital del Centro Comprensivo de Cancer de la UPR /ID# 222544	San Juan
Puerto Rico	VA Caribbean Healthcare System /ID# 222416	San Juan
Spain	Hospital Universitario Germans Trias i Pujol /ID# 214704	Badalona	Barcelona
Spain	Hospital Universitario Vall d'Hebron /ID# 222415	Barcelona
Spain	CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 230719	Madrid
Spain	Hospital General Universitario Gregorio Maranon /ID# 214676	Madrid
Spain	Hospital Universitario 12 de Octubre /ID# 214710	Madrid
Spain	Hospital Universitario Virgen de la Victoria /ID# 214709	Malaga
Spain	Hospital Regional de Malaga /ID# 230858	Málaga	Malaga
Spain	CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 230718	Pamplona	Navarra
Taiwan	Kaohsiung Chang Gung Memorial Hospital /ID# 230371	Kaohsiung City	Kaohsiung
Taiwan	National Cheng Kung University Hospital /ID# 230372	Tainan
United Kingdom	Belfast Health and Social Care Trust /ID# 216991	Belfast
United Kingdom	Guys and St Thomas NHS Foundation Trust /ID# 164110	London	London, City Of
United Kingdom	The Christie Hospital /ID# 164111	Manchester
United Kingdom	Aneurin Bevan University Health Board /ID# 230332	Newport
United Kingdom	Oxford University Hospitals NHS Foundation Trust /ID# 214503	Oxford	Oxfordshire
United States	Texas Oncology - West Texas /ID# 224784	Abilene	Texas
United States	Bend Memorial Clinic /ID# 224184	Bend	Oregon
United States	American Oncology Partners of Maryland, PA /ID# 231299	Bethesda	Maryland
United States	UAB Comprehensive Cancer Cente /ID# 165464	Birmingham	Alabama
United States	Dana-Farber Cancer Institute /ID# 162675	Boston	Massachusetts
United States	TOI Clinical Research /ID# 222546	Cerritos	California
United States	Medical University of South Carolina /ID# 222597	Charleston	South Carolina
United States	University of Chicago Medicine /ID# 164115	Chicago	Illinois
United States	The Ohio State University /ID# 217402	Columbus	Ohio
United States	Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 225159	Dallas	Texas
United States	Colorado Blood Cancer Institute /ID# 224250	Denver	Colorado
United States	Henry Ford Hospital /ID# 162682	Detroit	Michigan
United States	City of Hope /ID# 221395	Duarte	California
United States	MD Anderson Cancer Center at Texas Medical Center /ID# 162683	Houston	Texas
United States	Oncology Consultants /ID# 230930	Houston	Texas
United States	Indiana Blood & Marrow Transpl /ID# 165075	Indianapolis	Indiana
United States	Baptist MD Anderson Cancer Center - Jacksonville /ID# 222548	Jacksonville	Florida
United States	Mayo Clinic /ID# 164201	Jacksonville	Florida
United States	MidAmerica Division, Inc. /ID# 222058	Kansas City	Missouri
United States	Moores Cancer Center at UC San Diego /ID# 164084	La Jolla	California
United States	Long Beach Memorial Medical Ct /ID# 230148	Long Beach	California
United States	University of Southern California /ID# 164095	Los Angeles	California
United States	Tennessee Oncology-Nashville Centennial /ID# 221410	Nashville	Tennessee
United States	Weill Cornell Medical College /ID# 162679	New York	New York
United States	Mid Illinois Hematology & Oncology Associates, Ltd /ID# 230536	Normal	Illinois
United States	West Penn Hospital /ID# 222618	Pittsburgh	Pennsylvania
United States	University of Utah /ID# 164116	Salt Lake City	Utah
United States	Utah Cancer Specialists Salt Lake Clinic /ID# 222806	Salt Lake City	Utah
United States	University of Texas Health San Antonio MD Anderson Cancer Center /ID# 164094	San Antonio	Texas
United States	Ascension Providence Southfield Cancer Center /ID# 223876	Southfield	Michigan
United States	Moffitt Cancer Center /ID# 164082	Tampa	Florida
United States	Prairie Lakes Healthcare System /ID# 224358	Watertown	South Dakota
United States	University of Massachusetts - Worcester /ID# 222547	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Croatia,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Puerto Rico,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who achieve Spleen Volume Reduction of greater than or equal to 35% (SVR35) from baseline	Reduction in spleen volume is measured by magnetic resonance imaging/computerized tomography (MRI/CT).	From Baseline (Week 0) through Week 24
Secondary	Percentage of participants achieving 50% Reduction in Total System Score (TSS)	TSS is assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0.	From Baseline (Week 0) through Week 24
Secondary	Anemia Response	The anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.	Every 12 weeks up to approximately 96 weeks
Secondary	Change in Grade of Bone Marrow Fibrosis	Bone marrow grading is assessed according to the European Consensus Grading System.	Through Week 96