Clinical trial NCT04669067: TL-895 and KRT-232 Study in Acute Myeloid Leukemia
Official title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of TL-895 Combined With KRT-232 in Patients With Relapsed/Refractory (R/R) FLT3+ Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: AML
TP53
FLT3+
Navtemadlin
Lead sponsor: Telios Pharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Kartos Therapeutics, Inc.
First posted: 2020-12-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates TL-895, a potent, orally available and highly selective irreversible tyrosine kinase inhibitor combined with navtemadlin (KRT-232), a novel oral small molecule inhibitor of MDM2 for the treatment of adults with FLT3 mutated Acute Myeloid Leukemia. Participants must be relapsed/refractory (e.g., having failed prior therapy) to be eligible for this study.


Eligibility criteria: Inclusion Criteria:

* TP53 wildtype AML
* Relapsed/Refractory to at least one prior therapy, one of which must have included a FLT-3 inhibitor
* FLT3 mutation (FLT3-TKD or FLT3-ITD)
* ECOG 0-2
* Adequate hematologic, hepatic, and renal functions

Exclusion Criteria:

* AML subtype 3
* Prior treatment with MDM2 antagonist therapies
* Eligible for HSCT

Primary outcomes:
measure: Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232
timeFrame: 13 months
measure: Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh)
timeFrame: 41 months
Secondary outcomes:
measure: Key Secondary Objective: To determine the overall response rate (ORR)
timeFrame: 41 months
measure: Key Secondary Objective: To determine the duration of CR/CRh response (DOR)
timeFrame: 41 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck School of Medicine
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Augusta
country: United States
facility: Georgia Cancer Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center, Division of Hematology Oncology and Cell Therapy
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center, Harold C. Simmons Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Sippy Downs
country: Australia
facility: University of Sunshine Coast-Sippy Downs
city: Sydney
country: Australia
facility: Westmead Hospital
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
city: Vienna
country: Austria
facility: Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology
city: Lille
country: France
facility: Claude Huriez Hospital
city: Lyon
country: France
facility: South Lyon Hospital Center
city: Marseille
country: France
facility: Paoli-Calmettes Institute
city: Nantes
country: France
facility: University Hospital of Nantes
city: Nice
country: France
facility: Hospital Center Universitaire De Nice
city: Paris
country: France
facility: Saint-Louis Hospital
city: Halle
country: Germany
facility: University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
state: Sachsen-Anhalt
city: Essen
country: Germany
facility: University Duisburg-Essen, University Hospital Essen, Department of Internal Medicine
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf, Department of Internal Medicine II
city: Hannover
country: Germany
facility: Hannover Medical School, Center for Internal Medicine, Clinic of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation
city: Jena
country: Germany
facility: University Hospital Jena, Clinic of Internal Medicine II, Department of Hematology and Medical Oncology
city: Ancona
country: Italy
facility: University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona, Haematology Clinic
city: Bologna
country: Italy
facility: Polyclinic S. Orsola-Malpighi, Operative Unit of Hematology
city: Meldola
country: Italy
facility: Romagnolo Scientific Institute of Meldola (IRST) S.r.l., Department of Oncology and Clinical and Experimental Haematology
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital, Department of Hemato-Oncology
city: Badalona
country: Spain
facility: University Hospital Germans Trias i Pujol, Department of Clinical Hematology
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Valencia
country: Spain
facility: University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology
city: València
country: Spain
facility: Hospital Universitario y Politécnico de La Fe
Study officials:
References: