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RecruitingInterventionalPhase 1/Phase 2

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)

NCT ID: NCT04835584Sponsor: Kartos Therapeutics, Inc.Last updated: 2022-03-21

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.

Arms & 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.

Outcome measures

Primary

  • 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

Secondary

  • CCyR rate

    Time frame: 12 months

  • MCyR rate

    Time frame: 47 months

  • Duration of response

    Time frame: 47 months

  • Rate of complete hematologic response (CHR)

    Time frame: 47 months

  • Progression-free survival (PFS) in each Arm

    Time frame: 47 months

  • Overall survival (OS) in each Arm

    Time frame: 47 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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.

Study locations (5)

University of Alabama Birmingham

Birmingham, Alabama, 35294

Recruiting

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912

Recruiting

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232

Recruiting

Texas Oncology- Sammons CC at Baylor

Dallas, Texas, 75246

Recruiting

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Recruiting