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, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Lanraplenib, LANRA, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
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
- 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; 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
Sites / Locations
- University of California Los Angeles (UCLA)Recruiting
- The Blood and Marrow Transplant Group of GeorgiaRecruiting
- University of Chicago Medical CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- Oregon Health and Science UniversityRecruiting
- Texas Oncology - Baylor Charles A. Sammons Cancer Center
- University of Texas MD Anderson Cancer CenterRecruiting
- Froedtert HospitalRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- Hospital Germans Trias i PujolRecruiting
- MD Anderson Cancer Center MadridRecruiting
- Hospital Universitari Vall d'HebrónRecruiting
- Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)Recruiting
- Hospital Clínic de BarcelonaRecruiting
- Hospital San Pedro de AlcantaraRecruiting
- Hospital Universitario Fundación Jiménez DíazRecruiting
- Hospital Universitari i Politècnic La Fe
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Part 1: Dose Escalation
Part 2: Expansion Cohort
Sequential cohorts of participants will receive escalating doses of lanraplenib (LANRA) once daily (QD) + gilteritinib QD in each 28 day cycle for determination of the maximally tolerated dose (MTD) / recommended Phase 2 dose (RP2D) of LANRA in combination with gilteritinib.
Following identification of the maximally tolerated dose (MTD) / recommended Phase 2 dose (RP2D) of lanraplenib (LANRA) in combination with gilteritinib in Part 1, an expansion cohort will enroll. The expansion cohort will receive LANRA in combination with gilteritinib at the MTD / RP2D once daily (QD) in each 28 day cycle.