A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis (REFINE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03222609|
Recruitment Status : Active, not recruiting
First Posted : July 19, 2017
Last Update Posted : March 3, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Myelofibrosis (MF)||Drug: Ruxolitinib Drug: Navitoclax||Phase 2|
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||191 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||October 31, 2017|
|Actual Primary Completion Date :||March 28, 2022|
|Estimated Study Completion Date :||February 2, 2029|
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).
Other Name: Jakafi
Other Name: ABT-263
Participants will be administered various doses of navitoclax once daily (QD)
Other Name: ABT-263
- Percentage of Participants who achieve Spleen Volume Reduction of greater than or equal to 35% (SVR35) from baseline [ Time Frame: From Baseline (Week 0) through Week 24 ]Reduction in spleen volume is measured by magnetic resonance imaging/computerized tomography (MRI/CT).
- Percentage of participants achieving 50% Reduction in Total System Score (TSS) [ Time Frame: From Baseline (Week 0) through Week 24 ]TSS is assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0.
- Anemia Response [ Time Frame: Every 12 weeks up to approximately 96 weeks ]The anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
- Change in Grade of Bone Marrow Fibrosis [ Time Frame: Through Week 96 ]Bone marrow grading is assessed according to the European Consensus Grading System.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03222609
|Study Director:||ABBVIE INC.||AbbVie|
|Other Study ID Numbers:||
2017-001398-17 ( EudraCT Number )
|First Posted:||July 19, 2017 Key Record Dates|
|Last Update Posted:||March 3, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||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.|
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
|Time Frame:||For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/|
|Access Criteria:||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/|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
Post-polycythemia vera MF (PPV-MF)
Post-essential thrombocythemia (PET-MF)
bone marrow fibrosis
Bone Marrow Diseases