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KRT-232 and TKI Study in Chronic Myeloid Leukemia

Sponsor
Kartos Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04835584
Collaborator
(none)
109
Enrollment
26
Locations
4
Arms
61.8
Anticipated Duration (Months)
4.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
109 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
May 7, 2021
Anticipated Primary Completion Date :
Dec 31, 2024
Anticipated Study Completion Date :
Jun 30, 2026

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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

    3. 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

    1. CCyR rate [12 months]

      The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B

    2. MCyR rate [47 months]

      The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C

    3. 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

    4. 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

    5. 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

    6. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy 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.

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Kartos Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kartos Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT04835584
    Other Study ID Numbers:
    • KRT-232-117
    First Posted:
    Apr 8, 2021
    Last Update Posted:
    Mar 21, 2022
    Last Verified:
    Mar 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Kartos Therapeutics, Inc.
    navtemadlin
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Dasatinib

    Study Results

    No Results Posted as of Mar 21, 2022