Description:
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.
Title
- Brief Title: KRT-232 and TKI Study in Chronic Myeloid Leukemia
- Official Title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With a Tyrosine Kinase Inhibitor (TKI) in Patients With Relapsed or Refractory Ph+ Chronic Myeloid Leukemia (CML)
Clinical Trial IDs
- ORG STUDY ID:
KRT-232-117
- NCT ID:
NCT04835584
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| KRT-232 | | Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP |
| Dasatinib | Dasatinib Zentiva | Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP |
| Nilotinib | Tasigna | Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP | Experimental | 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. | - KRT-232
- Dasatinib
- Nilotinib
|
| Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP) | Experimental | 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 B (KRT-232 combined with Nilotinib in patients with CML-CP) | Experimental | 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) | Experimental | 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. | - KRT-232
- Dasatinib
- Nilotinib
|
Eligibility Criteria
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 2 prior
TKIs.
- 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 history of T315I mutation.
- Prior treatment with MDM2 antagonist therapies.
- Intolerance to current TKI therapy.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | DLTs will be used to establish the MTD/MAD of KRT-232 in combination with dasatinib or nilotinib |
Secondary Outcome Measures
| Measure: | MCyR rate |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B |
| Measure: | MCyR rate |
| Time Frame: | 47 months |
| Safety Issue: | |
| Description: | The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C |
| Measure: | Duration of response |
| Time Frame: | 47 months |
| Safety Issue: | |
| Description: | DOR (Kaplan-Meier estimate) defined as the time from first observation of response to progression/relapse or death, whichever comes first |
| Measure: | Rate of complete hematologic response (CHR) |
| Time Frame: | 47 months |
| Safety Issue: | |
| Description: | The proportion of subjects who achieve a CHR according to modified ELN criteria in Arms A and B |
| Measure: | Progression-free survival (PFS) in each Arm |
| Time Frame: | 47 months |
| Safety Issue: | |
| Description: | PFS is defined as the time from the first treatment dose date to progression/relapse or death, whichever comes first |
| Measure: | Overall survival (OS) in each Arm |
| Time Frame: | 47 months |
| Safety Issue: | |
| Description: | OS is defined as the time from the first treatment dose date to death from any cause |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Kartos Therapeutics, Inc. |
Trial Keywords
Last Updated
August 5, 2021
