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KRT-232 and TKI Study in Chronic Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT04835584
Recruitment Status : Recruiting
First Posted : April 8, 2021
Last Update Posted : August 5, 2021
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: KRT-232 Drug: Dasatinib Drug: Nilotinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 133 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
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : June 30, 2026


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 Name: Dasatinib Zentiva

Drug: Nilotinib
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Other Name: 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 Name: 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 Name: 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 Name: Dasatinib Zentiva

Drug: Nilotinib
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Other Name: Tasigna




Primary Outcome Measures :
  1. 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

  2. Part 2, Arm A and B: Major cytogenetic response (MCyR) 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

  3. 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


Secondary Outcome Measures :
  1. MCyR rate [ Time Frame: 12 months ]
    The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B

  2. MCyR rate [ Time Frame: 47 months ]
    The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C

  3. 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

  4. 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

  5. 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

  6. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04835584


Contacts
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Contact: John Mei 650-542-0136 jmei@kartosthera.com
Contact: Emily Houlihan 650-839-7293 ehoulihan@kartosthera.com

Locations
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United States, Georgia
Georgia Cancer Center at Augusta University Recruiting
Augusta, Georgia, United States, 30912
France
Centre Leon Berard Recruiting
Lyon, France, 69008
Poland
Pratia Onkologia Katowice Recruiting
Katowice, Poland, 40-519
Spain
Clínica Universidad de Navarra Recruiting
Madrid, Navarra, Spain, 28027
Clinica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Sponsors and Collaborators
Kartos Therapeutics, Inc.
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Responsible Party: Kartos Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04835584    
Other Study ID Numbers: KRT-232-117
First Posted: April 8, 2021    Key Record Dates
Last Update Posted: August 5, 2021
Last Verified: August 2021

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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:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action