A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
- Interventional
- Recruiting
- NCT05028751
Contact Information
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
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).
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
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
- 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