Chronic Myeloid Leukemia
Conditions
Keywords
navtemadlin
Brief summary
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with Ph+ Chronic Myeloid Leukemia (CML) who have relapsed or are refractory or intolerant to a Tyrosine Kinase Inhibitor (TKI). This study is a global, open label Phase 1b/2 to determine the efficacy and safety of KRT-232 in patients with chronic phase CML (CML-CP) and accelerated phase (CML-AP) who have failed TKI treatments.
Interventions
DRUGKRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
DRUGDasatinib
Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
DRUGNilotinib
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
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
* Phase 1b and Phase 2 Arms A and B: Documented TP53wt, Ph+, BCR-ABL+ CML-CP * Phase 2 Arm C ONLY: Documented TP53wt, Ph+, BCR-ABL+ CML-AP * Subject is resistant (relapsed or refractory) and/or intolerant to at least 1 prior TKI. * Adults ≥ 18 years of age. * ECOG performance status of 0 to 2 * Adequate hematologic, hepatic, and renal functions
Exclusion criteria
* Phase 1b and Phase 2 Arms A and B: Documented Ph+, BCR-ABL+ CML-AP * Documented Ph+, BCR-ABL+ CML-BC * Known T315I mutation. * Prior treatment with MDM2 antagonist therapies. * Intolerance to current TKI therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232 | 28 Days | DLTs will be used to establish the MTD/MAD of KRT-232 in combination with dasatinib or nilotinib |
| Part 2, Arm A and B: Major molecular response (MMR) rate | 6 months | The proportion of subjects who achieved complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) according to modified ELN criteria |
| Part 2, Arm C: Major hematological response (MaHR) rate | 6 months | The proportion of subjects who achieved MaHR according to modified ELN criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of complete hematologic response (CHR) | 47 months | The proportion of subjects who achieve a CHR according to modified ELN criteria in Arms A and B |
| CCyR rate | 12 months | The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B |
| Overall survival (OS) in each Arm | 47 months | OS is defined as the time from the first treatment dose date to death from any cause |
| Progression-free survival (PFS) in each Arm | 47 months | PFS is defined as the time from the first treatment dose date to progression/relapse or death, whichever comes first |
| MCyR rate | 47 months | The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C |
| Duration of response | 47 months | DOR (Kaplan-Meier estimate) defined as the time from first observation of response to progression/relapse or death, whichever comes first |
Countries
Canada, France, Italy, Poland, Russia, South Korea, Spain, United States
Contacts
Primary ContactJohn Mei
Outcome results
None listed