Primary objective: To evaluate the effect of navitoclax in combination with ruxolitinib on splenomegaly response when compared to ruxolitinib in subjects with myelofibrosis.Secondary objectives:• To evaluate the effect of navitoclax in combination…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or
Computed Tomography (CT), per International Working Group (IWG) criteria at
week 24
Secondary outcome
Secondary Efficacy Endpoints:
• Reduction in total symptom score (TSS) at Week 24 from baseline as measured
by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0
• Duration of SVR35
• Change in fatigue at Week 24 from baseline as measured by the PROMIS Fatigue
SF 7a
• Change in physical functioning, as measured by the physical functioning
domain of the EORTC QLQ-C30, or death
• Anemia response per IWG criteria
• At least 35% reduction in spleen volume from baseline (SVR35) as measured by
MRI or CT scan, per IWG criteria
• Reduction in grade of bone marrow fibrosis from baseline as measured by the
European consensus grading system
• Overall survival
• Leukemia-free survival
• Overall response of clinical improvement per IWG criteria.
Background 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.
Study objective
Primary objective:
To evaluate the effect of navitoclax in combination with ruxolitinib on
splenomegaly response when compared to ruxolitinib in subjects with
myelofibrosis.
Secondary objectives:
• To evaluate the effect of navitoclax in combination with ruxolitinib on the
onset, magnitude, and duration of disease response, including Total
Symptom Score (TSS), effects on spleen, bone marrow fibrosis, and anemia.
• To evaluate the effect of navitoclax in combination with ruxolitinib on
measures of health-related quality of life (HRQoL), including fatigue, and
physical functioning.
• To evaluate the effect of navitoclax in combination with ruxolitinib on
overall survival (OS) and leukemia-free survival.
Study design
Randomized, double-blind, placebo controlled
Intervention
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 till the participant cannot tolerate the study drug, or
benefit is not achieved, or other reasons which qualify for discontinuation of
the study drug
Study burden and risks
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), bone marrow tests, checking for side effects, and completing
questionnaires
Wegalaan 9
Hoofddorp 2132JD
NL
Wegalaan 9
Hoofddorp 2132JD
NL
Listed location countries
Age
Inclusion criteria
• Subject >= 18 years of age.
• Subject with a documented diagnosis of primary myelofibrosis (MF) or
secondary MF (post polycythemia vera [PPV] -MF or post essential
thrombocythemia [PET] - MF) as defined by the World Health Organization
classification.
• Subject must be able to complete the Myelofibrosis Symptom Assessment Form
(MFSAF) on at least 4 out of the 7 days immediately preceding the date of
randomisation
- Subject classified as intermediate-2 or high-risk MF as defined by the
Dynamic International Prognostic Scoring System Plus (DIPSS+).
• Subject has splenomegaly defined as spleen palpation measurement >= 5 cm below
costal margin or spleen volume >= 450 cm^3 as assessed centrally by MRI or CT
scan.
• Subject has at least 2 symptoms measurable (score >= 3) or a total score of >=
12, as measured by the MFSAF v4.0.
• Subject with an Eastern Cooperative Oncology Group (ECOG) performance status
of 0, 1, or 2.
Exclusion criteria
• Subject must not have received prior treatment with a JAK-2 inhibitor.
• Subject must not have received prior treatment with a BH3-mimetic compound or
bromodomain and extra-terminal motif (BET) inhibitor.
• Subject must not be eligible 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.
• Subject must not receive 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-000097-15-NL |
| ClinicalTrials.gov | NCT04472598 |
| CCMO | NL73951.042.20 |