KRT-232 and TKI Study in Chronic Myeloid Leukemia
- Conditions
- Chronic Myeloid Leukemia
- Interventions
- Registration Number
- NCT04835584
- Lead Sponsor
- Kartos Therapeutics, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 109
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP KRT-232 KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. TKI (dasatinib or nilotinib) will be administered orally, per locally prescribed dose and schedule. Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP) KRT-232 KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Nilotinib will be administered orally, per locally prescribed dose and schedule. Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP) KRT-232 KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasatinib or Nilotinib will be administered orally, per locally prescribed dose and schedule. Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP) KRT-232 KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasastinib will be administered orally, per locally prescribed dose and schedule. Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP) Dasatinib KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasastinib will be administered orally, per locally prescribed dose and schedule. Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP Nilotinib KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. TKI (dasatinib or nilotinib) will be administered orally, per locally prescribed dose and schedule. Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP Dasatinib KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. TKI (dasatinib or nilotinib) will be administered orally, per locally prescribed dose and schedule. Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP) Nilotinib KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Nilotinib will be administered orally, per locally prescribed dose and schedule. Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP) Dasatinib KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasatinib or Nilotinib will be administered orally, per locally prescribed dose and schedule. Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP) Nilotinib KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasatinib or Nilotinib will be administered orally, per locally prescribed dose and schedule.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method CCyR rate 12 months The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B
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
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
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
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
Trial Locations
- Locations (26)
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Azienda Ospedaliero - Universitaria Mater Domini
🇮🇹Catanzaro, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
National Medical Research Center of Hematology
🇷🇺Moscow, Russian Federation
Georgia Cancer Center at Augusta University
🇺🇸Augusta, Georgia, United States
Texas Oncology- Sammons CC at Baylor
🇺🇸Dallas, Texas, United States
APHM Hopital de la Timone
🇫🇷Marseille, France
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
🇮🇹Meldola FC, Italy
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Institut Paoli-Calmettes
🇫🇷Marseille, France
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Clínica Universidad de Navarra
🇪🇸Madrid, Navarra, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Centre Hospitalier Lyon Sud
🇫🇷Saint-Genis-Laval, France
Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda
🇮🇹Milano, MI, Italy
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Almazov National Medical Research Center
🇷🇺Saint Petersburg, Russian Federation
Samara State Medical University
🇷🇺Samara, Russian Federation
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Centre Leon Berard
🇫🇷Lyon, France
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain