The trial is taking place at:
H

Hospital Universitario Virgen de la Victoria | Cardiology Department

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

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AbbVie

Status and phase

Active, not recruiting
Phase 2

Conditions

Myelofibrosis (MF)

Treatments

Drug: Navitoclax
Drug: Ruxolitinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT03222609
2017-001398-17 (EudraCT Number)
M16-109

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

191 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

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

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

191 participants in 2 patient groups

Navitoclax + ruxolitinib
Experimental group
Description:
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).
Treatment:
Drug: Ruxolitinib
Drug: Navitoclax
Navitoclax
Experimental group
Description:
Participants will be administered various doses of navitoclax once daily (QD)
Treatment:
Drug: Navitoclax

Trial contacts and locations

150

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Data sourced from clinicaltrials.gov

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