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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03222609




Registration number
NCT03222609
Ethics application status
Date submitted
17/07/2017
Date registered
19/07/2017

Titles & IDs
Public title
A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis
Scientific title
A Phase 2 Open-Label Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Subjects With Myelofibrosis (REFINE)
Secondary ID [1] 0 0
2017-001398-17
Secondary ID [2] 0 0
M16-109
Universal Trial Number (UTN)
Trial acronym
REFINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis (MF) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Navitoclax

Experimental: Navitoclax + ruxolitinib - Participants will be administered navitoclax once daily (QD) at various doses and a dose greater than or equal to 10 mg of ruxolitinib twice daily (BID).

Experimental: Navitoclax - Participants will be administered various doses of navitoclax once daily (QD)


Treatment: Drugs: Ruxolitinib
Tablet; Oral

Treatment: Drugs: Navitoclax
Tablet; Oral
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants who achieve Spleen Volume Reduction of greater than or equal to 35% (SVR35) from baseline
Timepoint [1] 0 0
From Baseline (Week 0) through Week 24
Secondary outcome [1] 0 0
Percentage of participants achieving 50% Reduction in Total System Score (TSS)
Timepoint [1] 0 0
From Baseline (Week 0) through Week 24
Secondary outcome [2] 0 0
Anemia Response
Timepoint [2] 0 0
Every 12 weeks up to approximately 96 weeks
Secondary outcome [3] 0 0
Change in Grade of Bone Marrow Fibrosis
Timepoint [3] 0 0
Through Week 96

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/01/2025
Actual
Sample size
Target
Accrual to date
Final
191
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
The Kinghorn Cancer Centre /ID# 214657 - Darlinghurst
Recruitment hospital [2] 0 0
Barwon Health /ID# 222430 - Geelong
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Ctr /ID# 218352 - Melbourne
Recruitment hospital [4] 0 0
Alfred Health /ID# 215545 - Melbourne
Recruitment hospital [5] 0 0
Fiona Stanley Hospital /ID# 216809 - Murdoch
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3220 - Geelong
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
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Alabama
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United States of America
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California
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Colorado
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Florida
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Illinois
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Indiana
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Maryland
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Massachusetts
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Michigan
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Missouri
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New York
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Canada
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Alberta
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Canada
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Ontario
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Canada
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Quebec
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Croatia
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Grad Zagreb
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Croatia
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Splitsko-dalmatinska Zupanija
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Greece
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Attiki
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Hungary
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Szabolcs-Szatmar-Bereg
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Hungary
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Budapest
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Israel
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Tel-Aviv
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Israel
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Yerushalayim
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Israel
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Ashdod
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Israel
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Nahariya
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Italy
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Lazio
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Italy
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Bergamo
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Italy
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Bologna
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Italy
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Brescia
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Italy
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Catania
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Italy
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Florence
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Italy
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Reggio Calabria
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Italy
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Varese
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Aichi
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Aomori
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Japan
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Fukuoka
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Japan
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Hokkaido
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Tokyo
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Japan
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Yamanashi
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Korea, Republic of
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Seoul
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Puerto Rico
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San Juan
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Spain
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Barcelona
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Spain
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Malaga
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Spain
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Navarra
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Spain
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Madrid
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Taiwan
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Kaohsiung
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Taiwan
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Tainan
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United Kingdom
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London, City Of
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United Kingdom
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Oxfordshire
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United Kingdom
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Belfast
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United Kingdom
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Manchester
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United Kingdom
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Newport

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
Available to whom?
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/
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/abbvie/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03222609