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

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Status and phase: Terminated; Phase 2; Phase 1

Conditions: Refractory Acute Myeloid Leukemia; Relapsed Acute Myeloid Leukemia; Acute Myeloid Leukemia

Treatments: Drug: Gilteritinib; Drug: Lanraplenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05028751

2022-001279-15 (EudraCT Number)

KB-LANRA- 1001

Details and patient eligibility

About

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).

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 4 patient groups

LANRA 20 mg QD + Gilteritinib 120 mg QD

Experimental group

Description:

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.

Treatment:

Drug: Lanraplenib

Drug: Gilteritinib

LANRA 40 mg QD + Gilteritinib 120 mg QD

Experimental group

Description:

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.

Treatment:

Drug: Lanraplenib

Drug: Gilteritinib

LANRA 60 mg QD + Gilteritinib 120 mg QD

Experimental group

Description:

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.

Treatment:

Drug: Lanraplenib

Drug: Gilteritinib

LANRA 90 mg QD + Gilteritinib 120 mg QD

Experimental group

Description:

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.

Treatment:

Drug: Lanraplenib

Drug: Gilteritinib