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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
109
Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232
DLTs will be used to establish the MTD/MAD of KRT-232 in combination with dasatinib or nilotinib
Time frame: 28 Days
Part 2, Arm A and B: Major molecular response (MMR) rate
The proportion of subjects who achieved complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) according to modified ELN criteria
Time frame: 6 months
Part 2, Arm C: Major hematological response (MaHR) rate
The proportion of subjects who achieved MaHR according to modified ELN criteria
Time frame: 6 months
CCyR rate
The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B
Time frame: 12 months
MCyR rate
The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C
Time frame: 47 months
Duration of response
DOR (Kaplan-Meier estimate) defined as the time from first observation of response to progression/relapse or death, whichever comes first
Time frame: 47 months
Rate of complete hematologic response (CHR)
The proportion of subjects who achieve a CHR according to modified ELN criteria in Arms A and B
Time frame: 47 months
Progression-free survival (PFS) in each Arm
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of Alabama Birmingham
Birmingham, Alabama, United States
RECRUITINGGeorgia Cancer Center at Augusta University
Augusta, Georgia, United States
RECRUITINGUniversity of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
RECRUITINGTexas Oncology- Sammons CC at Baylor
Dallas, Texas, United States
RECRUITINGMedical College of Wisconsin
Milwaukee, Wisconsin, United States
RECRUITINGPrincess Margaret Cancer Center
Toronto, Ontario, Canada
RECRUITINGCentre Leon Berard
Lyon, France
RECRUITINGAPHM Hopital de la Timone
Marseille, France
RECRUITINGInstitut Paoli-Calmettes
Marseille, France
RECRUITINGCentre Hospitalier Lyon Sud
Saint-Genis-Laval, France
RECRUITING...and 16 more locations
PFS is defined as the time from the first treatment dose date to progression/relapse or death, whichever comes first
Time frame: 47 months
Overall survival (OS) in each Arm
OS is defined as the time from the first treatment dose date to death from any cause
Time frame: 47 months