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

• ClinicalTrials.gov Identifier: NCT05028751
• Recruitment Status: Recruiting
• First Posted: August 31, 2021
• Last Update Posted: December 19, 2022
• Sponsor: Kronos Bio
• Information provided by (Responsible Party): Kronos Bio

Tracking Information

• First Submitted Date: August 25, 2021
• First Posted Date: August 31, 2021
• Last Update Posted Date: December 19, 2022
• Actual Study Start Date: August 5, 2022
• Estimated Primary Completion Date: November 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2022)

• Part 1 and Part 2: Number of Participants who Experience a Treatment-Emergent Adverse Event (TEAE) [ Time Frame: Cycle 1 Day 1 through 30 days after last dose (up to approximately 5 years; cycle is 28 days) ]
• Part 1 and Part 2: Number of Participants who Experience a Dose-Limiting Toxicity (DLT) for Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through pre-dose Cycle 2 Day 1 (cycle is 28 days) ]
• Part 1: Maximally Tolerated Dose (MTD) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]
• Part 1: Recommended Phase 2 Dose (RP2D) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]

Original Primary Outcome Measures (submitted: August 25, 2021)

• Part 1 and 2: Number of Participants who Experience a Treatment-Emergent Adverse Event (TEAE) [ Time Frame: Cycle 1 Day 1 through 30 days after last dose (up to approximately 5 years; cycle is 28 days) ]
• Part 1 and Part 2: Number of Participants who Experience a Dose-Limiting Toxicity (DLT) for Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through pre-dose Cycle 2 Day 1 (cycle is 28 days) ]
• Part 1: Maximally Tolerated Dose (MTD) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]
• Part 1: Recommended Phase 2 Dose (RP2D) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]

Current Secondary Outcome Measures (submitted: August 25, 2021)

• Part 1: Maximal Plasma Concentration (Cmax) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]
• Part 1: Time to Maximal Plasma Concentration (Tmax) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]
• Part 1: Area Under the Plasma Concentration x Time Curve from Hour 0 to the Last Measurable Time Point (AUC0-last) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]
• Part 1 and Part 2: Composite Complete Response (CR) Rate [ Time Frame: Up to 5 years ]
• Part 1 and Part 2: Composite Complete Response (CR) with Partial Hematologic Recovery (CRh) [ Time Frame: Up to 5 years ]
• Part 1 and Part 2: Duration of Response (DoR) [ Time Frame: Up to 5 years ]
• Part 1 and Part 2: Event Free Survival (EFS) [ Time Frame: Up to 5 years ]
• Part 1 and Part 2: Overall Survival (OS) [ Time Frame: Up to 5 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
• Official Title: 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Myeloid Leukemia
• Relapsed Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Intervention

• Drug: Lanraplenib
  Orally via tablets
  Other Name: LANRA
• Drug: Gilteritinib
  Orally via tablets
  Other Name: XOSPATA®

Study Arms

• Experimental: Part 1: Dose Escalation
  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.
  Interventions:

  • Drug: Lanraplenib
  • Drug: Gilteritinib
• Experimental: Part 2: Expansion Cohort
  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.
  Interventions:

  • Drug: Lanraplenib
  • Drug: Gilteritinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 25, 2021): 55
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: November 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Director of Clinical Operations; 650-484-1583; clinicaltrials@kronosbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05028751
• Other Study ID Numbers: KB-LANRA- 1001; 2022-001279-15 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Kronos Bio
• Original Responsible Party: Same as current
• Current Study Sponsor: Kronos Bio
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Kronos Bio
• Verification Date: December 2022