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KRT-232 and TKI Study in Chronic Myeloid Leukemia

Primary Purpose

Chronic Myeloid Leukemia

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
KRT-232
Dasatinib
Nilotinib
Sponsored by
Kartos Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring navtemadlin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama BirminghamRecruiting
  • Georgia Cancer Center at Augusta UniversityRecruiting
  • University of Pittsburgh Medical CenterRecruiting
  • Texas Oncology- Sammons CC at BaylorRecruiting
  • Medical College of WisconsinRecruiting
  • Princess Margaret Cancer CenterRecruiting
  • Centre Leon BerardRecruiting
  • APHM Hopital de la TimoneRecruiting
  • Institut Paoli-CalmettesRecruiting
  • Centre Hospitalier Lyon SudRecruiting
  • Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' GrandaRecruiting
  • Azienda Ospedaliero - Universitaria Mater DominiRecruiting
  • Istituto Romagnolo per lo Studio dei Tumori Dino AmadoriRecruiting
  • Fondazione IRCCS Policlinico San MatteoRecruiting
  • Kyungpook National University HospitalRecruiting
  • Samsung Medical CenterRecruiting
  • Seoul National University HospitalRecruiting
  • Severance HospitalRecruiting
  • Pratia Onkologia KatowiceRecruiting
  • National Medical Research Center of HematologyRecruiting
  • Almazov National Medical Research CenterRecruiting
  • Samara State Medical UniversityRecruiting
  • Clínica Universidad de NavarraRecruiting
  • Clinica Universidad de NavarraRecruiting
  • Hospital Universitari Vall d'HebronRecruiting
  • Hospital Universitario La PazRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP

Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP)

Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP)

Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP)

Arm Description

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 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.

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.

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.

Outcomes

Primary Outcome Measures

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
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
Part 2, Arm C: Major hematological response (MaHR) rate
The proportion of subjects who achieved MaHR according to modified ELN criteria

Secondary Outcome Measures

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

Full Information

First Posted
April 5, 2021
Last Updated
March 4, 2022
Sponsor
Kartos Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04835584
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 7, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kartos Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia
Keywords
navtemadlin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
109 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
KRT-232
Intervention Description
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
Dasatinib Zentiva
Intervention Description
Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Intervention Type
Drug
Intervention Name(s)
Nilotinib
Other Intervention Name(s)
Tasigna
Intervention Description
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
Primary Outcome Measure Information:
Title
Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232
Description
DLTs will be used to establish the MTD/MAD of KRT-232 in combination with dasatinib or nilotinib
Time Frame
28 Days
Title
Part 2, Arm A and B: Major molecular response (MMR) rate
Description
The proportion of subjects who achieved complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) according to modified ELN criteria
Time Frame
6 months
Title
Part 2, Arm C: Major hematological response (MaHR) rate
Description
The proportion of subjects who achieved MaHR according to modified ELN criteria
Time Frame
6 months
Secondary Outcome Measure Information:
Title
CCyR rate
Description
The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B
Time Frame
12 months
Title
MCyR rate
Description
The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C
Time Frame
47 months
Title
Duration of response
Description
DOR (Kaplan-Meier estimate) defined as the time from first observation of response to progression/relapse or death, whichever comes first
Time Frame
47 months
Title
Rate of complete hematologic response (CHR)
Description
The proportion of subjects who achieve a CHR according to modified ELN criteria in Arms A and B
Time Frame
47 months
Title
Progression-free survival (PFS) in each Arm
Description
PFS is defined as the time from the first treatment dose date to progression/relapse or death, whichever comes first
Time Frame
47 months
Title
Overall survival (OS) in each Arm
Description
OS is defined as the time from the first treatment dose date to death from any cause
Time Frame
47 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Mei
Phone
650-542-0136
Email
jmei@kartosthera.com
Facility Information:
Facility Name
University of Alabama Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Name
Georgia Cancer Center at Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Oncology- Sammons CC at Baylor
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Name
Princess Margaret Cancer Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C1
Country
Canada
Individual Site Status
Recruiting
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Recruiting
Facility Name
APHM Hopital de la Timone
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Recruiting
Facility Name
Institut Paoli-Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Lyon Sud
City
Saint-Genis-Laval
ZIP/Postal Code
69310
Country
France
Individual Site Status
Recruiting
Facility Name
Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Individual Site Status
Recruiting
Facility Name
Azienda Ospedaliero - Universitaria Mater Domini
City
Catanzaro
ZIP/Postal Code
88100
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
City
Meldola FC
ZIP/Postal Code
47014
Country
Italy
Individual Site Status
Recruiting
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Individual Site Status
Recruiting
Facility Name
Kyungpook National University Hospital
City
Daegu
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Severance Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Pratia Onkologia Katowice
City
Katowice
ZIP/Postal Code
40-519
Country
Poland
Individual Site Status
Recruiting
Facility Name
National Medical Research Center of Hematology
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Almazov National Medical Research Center
City
Saint Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Samara State Medical University
City
Samara
ZIP/Postal Code
443001
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Clínica Universidad de Navarra
City
Madrid
State/Province
Navarra
ZIP/Postal Code
28027
Country
Spain
Individual Site Status
Recruiting
Facility Name
Clinica Universidad de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

KRT-232 and TKI Study in Chronic Myeloid Leukemia

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