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

• Status: Not yet recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kronos Bio

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

• 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

• Failure to achieve at least a partial response (PR) or have relapsed following prior exposure to gilteritinib or other next-generation FLT3 inhibitor monotherapy (eg. quizartinib, crenolanib)

• 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 known 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; 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 cirrhosis, 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