Clinical trial NCT04835584: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Myeloid Leukemia
Keywords: navtemadlin
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-08
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232
timeFrame: 28 Days
measure: Part 2, Arm A and B: Major molecular response (MMR) rate
timeFrame: 6 months
measure: Part 2, Arm C: Major hematological response (MaHR) rate
timeFrame: 6 months
Secondary outcomes:
measure: CCyR rate
timeFrame: 12 months
measure: MCyR rate
timeFrame: 47 months
measure: Duration of response
timeFrame: 47 months
measure: Rate of complete hematologic response (CHR)
timeFrame: 47 months
measure: Progression-free survival (PFS) in each Arm
timeFrame: 47 months
measure: Overall survival (OS) in each Arm
timeFrame: 47 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology- Sammons CC at Baylor
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: APHM Hopital de la Timone
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Saint-Genis-Laval
country: France
facility: Centre Hospitalier Lyon Sud
city: Milano
country: Italy
facility: Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda
state: MI
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero - Universitaria Mater Domini
city: Meldola FC
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Moscow
country: Russian Federation
facility: National Medical Research Center of Hematology
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Center
city: Samara
country: Russian Federation
facility: Samara State Medical University
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
References: