A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Navitoclax in Combination with Ruxolitinib Versus Ruxolitinib in Subjects with Myelofibrosis (TRANSFORM-1)
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.
- 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 Thrombocytopenia [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.
- 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