A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase 1b/2 Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of the Selective SYK Inhibitor Lanraplenib (LANRA) in Combination With the FLT3 Inhibitor Gilteritinib, in Patients With FLT3-mutated Relapsed or Refractory AML

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05028751
• Other study ID #: KB-LANRA- 1001
• Secondary ID: 2022-001279-15
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 5, 2022
• Est. completion date: April 9, 2024

Study information

• Verified date: April 2024
• Source: Kronos Bio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the safety of lanraplenib (LANRA) in combination with the FMS-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib, in participants with relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: April 9, 2024
• Est. primary completion date: April 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults =18 years of age with acute myeloid leukemia (AML) and at least 1 prior line of therapy
• FMS-like tyrosine kinase 3 (FLT3)-mutated disease documented in a local reference laboratory at the time of consideration for enrollment in the study
• Have the ability to understand the requirements and procedures of the study and sign a written informed consent form
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
• Adequate hepatic and renal function
• Prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR) =1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
• Negative serum ß-human chorionic gonadotropin (HCG) test in women of child-bearing potential (WOCBP)
• Left ventricular ejection fraction =50% confirmed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan

Exclusion Criteria:

• Known central nervous system (CNS) involvement with leukemia
• Clinical signs/symptoms of leukostasis that have failed therapy including hydroxyurea and/or leukapheresis of at least 3 days duration
• Pregnant or breastfeeding women
• Active infection with hepatitis B, C or human immunodeficiency virus (HIV) infection
• Disseminated intravascular coagulation with active bleeding or signs of thrombosis
• Known active coronavirus disease 2019 (COVID-19)
• Administration of a live attenuated virus vaccine within 35 days before Cycle 1 Day 1 (C1D1)
• History of non-myeloid malignancy except for the following: adequately treated localized basal cell, or squamous cell carcinoma of the skin, or localized melanoma (with TNM stage either Tis [melanoma in-situ] or T1aN0M0) with complete resection; cervical carcinoma in situ; superficial bladder cancer; asymptomatic prostate cancer without known metastatic disease, with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for > 1 year prior to start of study therapy; or any other cancer that has been in complete remission without treatment for =3 years prior to enrollment
• Clinically significant heart disease
• Prolongation of the congenital long measure between Q wave and T wave in the electrocardiogram (QT) interval at baseline
• Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection at the time of study treatment initiation
• Current (within 30 days of study enrollment) drug-induced liver injury, chronic active hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis, primary biliary cholangitis with inadequate response to ursodeoxycholic acid or other health authority approved therapy, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, orportal hypertension
• Ongoing (within 6 weeks of study enrollment) hepatic encephalopathy
• Ongoing immunosuppressive therapy, including systemic chemotherapy for treatment of leukemia

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Refractory Acute Myeloid Leukemia
• Relapsed Acute Myeloid Leukemia

Intervention

Drug:
• Lanraplenib
Orally via tablets
• Gilteritinib
Orally via tablets

Locations

Country	Name	City	State
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Germans Trias i Pujol	Barcelona	Badalona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)	Barcelona
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Hospital Universitario 12 de Octubre	Madrid	Avenida De Córdoba Sin Número
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid	Calle De Arturo Soria
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United States	The Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California Los Angeles (UCLA)	Los Angeles	California
United States	Froedtert Hospital	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oregon Health and Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Kronos Bio

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 and Part 2: Number of Participants who Experience a Treatment-Emergent Adverse Event (TEAE)		Cycle 1 Day 1 through 30 days after last dose (up to approximately 5 years; cycle is 28 days)
Primary	Part 1 and Part 2: Number of Participants who Experience a Dose-Limiting Toxicity (DLT) for Lanraplenib (LANRA)		Cycle 1 Day 1 through pre-dose Cycle 2 Day 1 (cycle is 28 days)
Primary	Part 1: Maximally Tolerated Dose (MTD) of Lanraplenib (LANRA)		Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)
Primary	Part 1: Recommended Phase 2 Dose (RP2D) of Lanraplenib (LANRA)		Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)
Secondary	Part 1: Maximal Plasma Concentration (Cmax) of Lanraplenib (LANRA)		Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)
Secondary	Part 1: Time to Maximal Plasma Concentration (Tmax) of Lanraplenib (LANRA)		Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)
Secondary	Part 1: Area Under the Plasma Concentration x Time Curve from Hour 0 to the Last Measurable Time Point (AUC0-last) of Lanraplenib (LANRA)		Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)
Secondary	Part 1 and Part 2: Composite Complete Response (CR) Rate		Up to 5 years
Secondary	Part 1 and Part 2: Composite Complete Response (CR) with Partial Hematologic Recovery (CRh)		Up to 5 years
Secondary	Part 1 and Part 2: Duration of Response (DoR)		Up to 5 years
Secondary	Part 1 and Part 2: Event Free Survival (EFS)		Up to 5 years
Secondary	Part 1 and Part 2: Overall Survival (OS)		Up to 5 years