KRT-232 and TKI Study in Chronic Myeloid Leukemia

March 4, 2022 updated by: Kartos Therapeutics, Inc.

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)

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

109

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C1
        • Recruiting
        • Princess Margaret Cancer Center
  • France
      • Lyon, France, 69008
        • Recruiting
        • Centre Leon Berard
      • Marseille, France, 13009
        • Recruiting
        • Institut Paoli-Calmettes
      • Marseille, France, 13005
        • Recruiting
        • APHM Hopital de la Timone
      • Saint-Genis-Laval, France, 69310
        • Recruiting
        • Centre Hospitalier Lyon Sud
  • Italy
      • Catanzaro, Italy, 88100
        • Recruiting
        • Azienda Ospedaliero - Universitaria Mater Domini
      • Meldola FC, Italy, 47014
        • Recruiting
        • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
      • Pavia, Italy, 27100
        • Recruiting
        • Fondazione IRCCS Policlinico San Matteo
    • MI
      • Milano, MI, Italy, 20122
        • Recruiting
        • Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda
  • Korea, Republic of
      • Daegu, Korea, Republic of
        • Recruiting
        • Kyungpook National University Hospital
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 135-710
        • Recruiting
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • Recruiting
        • Severance Hospital
  • Poland
      • Katowice, Poland, 40-519
        • Recruiting
        • Pratia Onkologia Katowice
  • Russian Federation
      • Moscow, Russian Federation, 125167
        • Recruiting
        • National Medical Research Center of Hematology
      • Saint Petersburg, Russian Federation, 197341
        • Recruiting
        • Almazov National Medical Research Center
      • Samara, Russian Federation, 443001
        • Recruiting
        • Samara State Medical University
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28046
        • Recruiting
        • Hospital Universitario La Paz
    • Navarra
      • Madrid, Navarra, Spain, 28027
        • Recruiting
        • Clinica Universidad de Navarra
      • Pamplona, Navarra, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama Birmingham
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Recruiting
        • Georgia Cancer Center at Augusta University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Medical Center
    • Texas
      • Dallas, Texas, United States, 75246
        • Recruiting
        • Texas Oncology- Sammons CC at Baylor
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP
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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Drug: Dasatinib
Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Other Names:
  • Dasatinib Zentiva
Drug: Nilotinib
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Other Names:
  • Tasigna
EXPERIMENTAL: Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP)
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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Drug: Dasatinib
Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Other Names:
  • Dasatinib Zentiva
EXPERIMENTAL: Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP)
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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Drug: Nilotinib
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Other Names:
  • Tasigna
EXPERIMENTAL: Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP)
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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Drug: Dasatinib
Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Other Names:
  • Dasatinib Zentiva
Drug: Nilotinib
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Other Names:
  • Tasigna

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232
Time Frame: 28 Days
DLTs will be used to establish the MTD/MAD of KRT-232 in combination with dasatinib or nilotinib
28 Days
Part 2, Arm A and B: Major molecular response (MMR) rate
Time Frame: 6 months
The proportion of subjects who achieved complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) according to modified ELN criteria
6 months
Part 2, Arm C: Major hematological response (MaHR) rate
Time Frame: 6 months
The proportion of subjects who achieved MaHR according to modified ELN criteria
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CCyR rate
Time Frame: 12 months
The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B
12 months
MCyR rate
Time Frame: 47 months
The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C
47 months
Duration of response
Time Frame: 47 months
DOR (Kaplan-Meier estimate) defined as the time from first observation of response to progression/relapse or death, whichever comes first
47 months
Rate of complete hematologic response (CHR)
Time Frame: 47 months
The proportion of subjects who achieve a CHR according to modified ELN criteria in Arms A and B
47 months
Progression-free survival (PFS) in each Arm
Time Frame: 47 months
PFS is defined as the time from the first treatment dose date to progression/relapse or death, whichever comes first
47 months
Overall survival (OS) in each Arm
Time Frame: 47 months
OS is defined as the time from the first treatment dose date to death from any cause
47 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kartos Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 7, 2021

Primary Completion (ANTICIPATED)

December 31, 2024

Study Completion (ANTICIPATED)

June 30, 2026

Study Registration Dates

First Submitted

April 5, 2021

First Submitted That Met QC Criteria

April 5, 2021

First Posted (ACTUAL)

April 8, 2021

Study Record Updates

Last Update Posted (ACTUAL)

March 21, 2022

Last Update Submitted That Met QC Criteria

March 4, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KRT-232-117

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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