Hospital Universitario Virgen de la Victoria | Cardiology Department
A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis (REFINE)
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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Participants with documented diagnosis of intermediate-2 or high-risk primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis.
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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.
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Eastern Cooperative Oncology Group (ECOG) of 0, 1, or 2.
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Prior treatment must meet at least one of the following criteria:
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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:
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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.
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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.
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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
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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
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No prior treatment with a JAK-2 or BET inhibitor.
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Participant has splenomegaly as defined in the protocol.
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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.
Trial design
Primary purpose
Allocation
Interventional model
Masking
191 participants in 2 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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