Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV-MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)
Conditions
Keywords
navtemadlin
Brief summary
This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF) The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.
Sponsors
Kartos Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO) * High-risk, or intermediate-1 and 2 risk, defined by Dynamic International Prognostic System (DIPSS) * ECOG of 0 or 1
Exclusion criteria
* Subjects who are positive for p53 mutation (Arm 1) * Prior MDM2 inhibitor therapy or p53-directed therapy (Arm 1) * Prior treatment with any JAK inhibitor * Prior splenectomy * Splenic irradiation within 24 weeks prior to randomization * Prior allogeneic stem-cell transplantation or plans for allogeneic stem-cell transplant * History of major organ transplant * Grade 2 or higher QTc prolongation * Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spleen Volume Reduction (SVR) | 24 weeks | The proportion of subjects achieving ≥35% SVR at Week 24 by MRI/CT (central review) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Total Symptom Score (TSS) | 24 weeks | The proportion of subjects who have at least a 50% reduction from Baseline to Week 24 in the total symptom score as measured by the MF-SAF v4.0 |
| Spleen Response Duration | 48 months | Time from initial SVR of ≥35% by MRI/CT (central review) until progression |
| Rate of conversion from RBC transfusion dependent to independent | 24 weeks | The proportion of subjects who convert from transfusion dependent to transfusion independent at Week 24 |
| Overall Survival (OS) | 48 months | Time from first dose to death from any cause |
| Progression free survival (PFS) | 48 months | Time from randomization to either first occurrence of disease progression or death due to any cause |
Countries
Belarus, Bulgaria, Georgia, Mexico, Poland, Russia, South Africa, Ukraine, United States
Contacts
Primary ContactJohn Mei
Backup ContactJordan Blevins
Outcome results
None listed