Phase 3
N=252
Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis
Myelofibrosis (MF)
Bottom Line
View on ClinicalTrials.gov: NCT04472598 ↗Enrolled (actual)
252
Serious AEs
38.9%
Results posted
Mar 2026
Primary outcome: Primary: Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume at Week 24 (SVR35W24) — 31.50; 63.20 percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Placebo for Navitoclax (Drug); Ruxolitinib (Drug); Navitoclax (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AbbVie
- Primary completion
- Apr 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume at Week 24 (SVR35W24) |
31.50; 63.20 | <0.0001 sig |
| SECONDARY Change From Baseline in Total Symptom Score (TSS) at Week 24 as Measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 |
-11.14; -9.71 | =0.2852 |
| SECONDARY Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume (SVR35) at Any Time |
44.09; 76.80 | <0.0001 sig |
| SECONDARY Duration of 35% Spleen Volume Reduction (SVR35) |
NA; NA | — |
| SECONDARY Change From Baseline In Fatigue at Week 24 as Measured by the PROMIS Fatigue Short Form (SF) 7a |
-3.63; -3.75 | =0.9029 |
| SECONDARY Change From Baseline at Week 24 in Physical Functioning as Measured by the Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 |
6.198; 7.326 | =0.6152 |
| SECONDARY Percentage of Participants Achieving Anemia Response |
30.56; 28.79; 29.41; 29.51; 50.00; 20.00 | =0.8524 |
| SECONDARY Overall Survival (OS) |
48.49; NA | =0.3867 |
| SECONDARY Leukemia-Free Survival |
NA; NA | =0.9706 |
| SECONDARY Percentage of Participants Who Achieved Reduction in Grade of Bone Marrow Fibrosis From Baseline at Any Time |
48.89; 56.52 | =0.3311 |
Summary
Myelofibrosis is a type of bone marrow cancer that usually develops slowly and disrupts body's normal production of blood cells. It causes bone marrow scarring, leading to severe anemia that can cause weakness and fatigue. It can also cause a low number of blood-clotting cells called platelets, which increases risk of bleeding. Myelofibrosis often causes an enlarged spleen. The purpose of this study is to see if a combination of navitoclax and ruxolitinib is more effective and safe in assessment of change in spleen volume when compared to ruxolitinib in participants with myelofibrosis.
Navitoclax is an investigational drug for the treatment of myelofibrosis. Participants in this study are divided into two groups, called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of myelofibrosis will be enrolled. Around 230 participants will be enrolled in approximately 190 sites worldwide.
Participants will receive oral navitoclax tablet with oral ruxolitinib tablet or oral ruxolitinib tablet with oral placebo (no active drug) tablet and treatment may continue untill the participant cannot tolerate the study drug, or benefit is not achieved, or other reasons which qualify for discontinuation of the study drug.
There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, magnetic resonance imaging (MRI) or computed tomography (CT) scan, bone marrow tests, checking for side effects, and completing questionnaires.
Eligibility Criteria
Inclusion Criteria
- Documented diagnosis of Primary MyeloFibrosis (MF) as defined by World Health Organization (WHO) classification or Secondary MF (post polycythemia vera [PPV] - MF or Post Essential Thrombocythemia [PET] - MF) .
- Must be able to complete the MF Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days immediately preceding the date of randomization.
-- Must have at least 2 symptoms with a score >=3 or a total score of >=12, as measured by the MFSAF v4.0.
- Classified as intermediate-2, or high-Risk MF as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
- Has splenomegaly defined as spleen palpation measurement >= 5 centimeters (cm) below costal margin or spleen volume greater than or equal to 450 cubic cm as assessed centrally by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
- Ineligible for stem cell transplantation at time of study entry due to age, comorbidities, or unfit for unrelated or unmatched donor transplant and other criteria per National Comprehensive Cancer Network guidelines.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Exclusion Criteria
- Prior treatment with a Janus Kinase-2 (JAK-2) inhibitor.
- Prior treatment with a B-cell lymphoma 2 homology 3 (BH3)-mimetic compound or bromodomain and extra-terminal motif (BET) inhibitor or stem cell transplant.
- Receiving medication that interferes with coagulation or platelet function within 3 days prior to the first dose of study drug or during the study treatment period except for low dose aspirin (up to 100 milligram daily) and low molecular weight heparin (LMWH).
Data sourced from ClinicalTrials.gov (NCT04472598). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.