KRT-232 and TKI Study in Chronic Myeloid Leukemia

Chronic Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04835584
• Other study ID #: KRT-232-117
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 7, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: March 2022
• Source: Kartos Therapeutics, Inc.
• Contact: John Mei
• Phone: 650-542-0136
• Email: jmei[@]kartosthera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 109
• Est. completion date: June 30, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
• Dasatinib
Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
• Nilotinib
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Center	Toronto	Ontario
France	Centre Leon Berard	Lyon
France	APHM Hopital de la Timone	Marseille
France	Institut Paoli-Calmettes	Marseille
France	Centre Hospitalier Lyon Sud	Saint-Genis-Laval
Italy	Azienda Ospedaliero - Universitaria Mater Domini	Catanzaro
Italy	Istituto Romagnolo per lo Studio dei Tumori Dino Amadori	Meldola FC
Italy	Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda	Milano	MI
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Poland	Pratia Onkologia Katowice	Katowice
Russian Federation	National Medical Research Center of Hematology	Moscow
Russian Federation	Almazov National Medical Research Center	Saint Petersburg
Russian Federation	Samara State Medical University	Samara
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Clínica Universidad de Navarra	Madrid	Navarra
Spain	Hospital Universitario La Paz	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
United States	Georgia Cancer Center at Augusta University	Augusta	Georgia
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Texas Oncology- Sammons CC at Baylor	Dallas	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Kartos Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	28 Days
Primary	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	6 months
Primary	Part 2, Arm C: Major hematological response (MaHR) rate	The proportion of subjects who achieved MaHR according to modified ELN criteria	6 months
Secondary	CCyR rate	The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B	12 months
Secondary	MCyR rate	The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C	47 months
Secondary	Duration of response	DOR (Kaplan-Meier estimate) defined as the time from first observation of response to progression/relapse or death, whichever comes first	47 months
Secondary	Rate of complete hematologic response (CHR)	The proportion of subjects who achieve a CHR according to modified ELN criteria in Arms A and B	47 months
Secondary	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	47 months
Secondary	Overall survival (OS) in each Arm	OS is defined as the time from the first treatment dose date to death from any cause	47 months