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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03222609




Registration number
NCT03222609
Ethics application status
Date submitted
17/07/2017
Date registered
19/07/2017
Date last updated
3/03/2023

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 at least 2 symptoms each with a score >=3 or a total score
of >= 12, as measured by the MFSAF v4.0 on at least 4 out of 7 days during
screening prior to study drug dosing.

- 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
2/02/2029
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
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Alabama
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California
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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
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 website
https://clinicaltrials.gov/ct2/show/NCT03222609
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03222609