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

NCT ID: NCT05028751

Last Updated: 2024-08-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-05
• Study Completion Date: 2024-04-09

Brief 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).

Conditions

Acute Myeloid Leukemia; Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LANRA 20 mg QD + Gilteritinib 120 mg QD

Participants received LANRA 20 mg once daily (QD) as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 1. Participants also received gilteritinib 120 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 2. Participants received treatment until progression/relapse or lack of at least a partial remission (PR) after 6 months of study treatment, intolerance, or withdrawal from treatment by the participant or study investigator.

Group Type: EXPERIMENTAL

Lanraplenib

Intervention Type: DRUG

Orally via tablets

Gilteritinib

Intervention Type: DRUG

Orally via tablets

LANRA 40 mg QD + Gilteritinib 120 mg QD

Participants received LANRA 40 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 1. Participants also received gilteritinib 120 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 2. Participants received treatment until progression/relapse or lack of at least a PR after 6 months of study treatment, intolerance, or withdrawal from treatment by the participant or study investigator.

Group Type: EXPERIMENTAL

Lanraplenib

Intervention Type: DRUG

Orally via tablets

Gilteritinib

Intervention Type: DRUG

Orally via tablets

LANRA 60 mg QD + Gilteritinib 120 mg QD

Participants received LANRA 60 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 1. Participants also received gilteritinib 120 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 2. Participants received treatment until progression/relapse or lack of at least a PR after 6 months of study treatment, intolerance, or withdrawal from treatment by the participant or study investigator.

Group Type: EXPERIMENTAL

Lanraplenib

Intervention Type: DRUG

Orally via tablets

Gilteritinib

Intervention Type: DRUG

Orally via tablets

LANRA 90 mg QD + Gilteritinib 120 mg QD

Participants received LANRA 90 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 1. Participants also received gilteritinib 120 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 2. Participants received treatment until progression/relapse or lack of at least a PR after 6 months of study treatment, intolerance, or withdrawal from treatment by the participant or study investigator.

Group Type: EXPERIMENTAL

Lanraplenib

Intervention Type: DRUG

Orally via tablets

Gilteritinib

Intervention Type: DRUG

Orally via tablets

Interventions

Lanraplenib

Orally via tablets

Intervention Type: DRUG

Gilteritinib

Orally via tablets

Intervention Type: DRUG

Other Intervention Names

LANRA; XOSPATA®

Eligibility Criteria

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 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, or portal hypertension
• Ongoing (within 6 weeks of study enrollment) hepatic encephalopathy
• Ongoing immunosuppressive therapy, including systemic chemotherapy for treatment of leukemia

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kronos Bio

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California Los Angeles (UCLA)

Los Angeles, California, United States

The Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Oregon Health and Science University

Portland, Oregon, 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

Froedtert Hospital

Milwaukee, Wisconsin, United States

Hospital Universitario 12 de Octubre

Madrid, Avenida de Córdoba Sin Número, Spain

Hospital Germans Trias i Pujol

Barcelona, Badalona, Spain

MD Anderson Cancer Center Madrid

Madrid, Calle de Arturo Soria, Spain

Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Countries

United States; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2022-001279-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KB-LANRA- 1001

Identifier Type: -

Identifier Source: org_study_id