Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis, Primary Myelofibrosis, MF
Conditions
Keywords
Navtemadlin, KRT-232, Ruxolitinib, POIESIS, TP53, Suboptimal response, Sub-optimal response
Brief summary
This clinical trial is evaluating whether addition of navtemadlin to ruxolitinib treatment will provide more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have a suboptimal response to ruxolitinib treatment alone. Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.
Interventions
DRUGNavtemadlin
Navtemadlin is an investigational MDM2 inhibitor
Navtemadlin placebo
DRUGRuxolitinib
Ruxolitinib is a janus kinase 1/2 inhibitor
Sponsors
Kartos Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Ruxolitinib Alone Period: * Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria * High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * JAK-inhibitor treatment naive
Exclusion criteria
for Ruxolitinib Alone Period: * Prior Splenectomy * Splenic irradiation within 3 months prior to the first dose * Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy * Eligible for Bone Marrow Transplant * Peripheral blood or bone marrow blast count ≥ 10 percent Inclusion Criteria for Randomized Period: * PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing * ECOG performance status of 0 to 2 * Treatment with a stable dose of ruxolitinib * Suboptimal response to run-in ruxolitinib treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To compare spleen volume reduction (SVR35) between Arm 1 and Arm 2 | 24 weeks | The proportion of subjects in each arm with SVR35 by MRI/CT scan (central review) 24 weeks after start of the randomized period |
| To compare total symptom score reduction (TSS50) between Arm 1 and Arm 2 | 24 weeks | The proportion of subjects in each arm with a TSS50 by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 24 weeks after start of the randomized period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare time to progression between Arm 1 and Arm 2 | Up to 8 years | Time to progression or death from any cause in subjects randomized to each arm |
| To compare overall survival (OS) between Arm 1 and Arm 2 | Up to 8 years | Time to death from any cause in subjects randomized to each arm |
Countries
Australia, Austria, Belgium, Croatia, Czechia, France, Georgia, Germany, Greece, Hungary, Italy, Poland, Portugal, Romania, Serbia, South Korea, Spain, United Kingdom, United States
Contacts
Primary ContactJohn Mei
Outcome results
None listed