Myelofibrosis
Conditions
Keywords
navtemadlin
Brief summary
This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in combination with ruxolitinib.
Interventions
DRUGKRT-232
administered by mouth
DRUGRuxolitinib
administered by mouth
Sponsors
Kartos Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) * Treatment with ruxolitinib for ≥18 weeks prior to study entry, and on a stable dose of ruxolitinib in the 8 weeks prior to study entry * Spleen ≥5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT * Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0 * ECOG performance status of 0 to 2
Exclusion criteria
* Patients who are positive for TP53 mutations * Documented disease progression or clinical deterioration any time while on ruxolitinib treatment * Patients who have had a documented spleen response to ruxolitinib. * Prior splenectomy * Prior MDM2 inhibitor therapy or p53-directed therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| For Phase 2:To determine the spleen volume reduction (SVR) at Week 24 | 6 months after last patient enrolled | The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan |
| For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib | 15 months | Dose limiting toxicities will be used to establish the MTD of KRT-232 in combination with ruxolitinib. Subsequently, RP2D will be based on safety and efficacy data of the combination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine spleen response | 43 months | The proportion of subjects achieving ≥35% SVR at any time point from Baseline while on study, as assessed by MRI (or by CT scan for applicable subjects) |
| To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) | 43 months | The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study |
Countries
Australia, Bulgaria, France, Germany, Israel, Italy, Poland, Spain, United States
Contacts
Primary ContactJohn Mei
Outcome results
None listed