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

Tracking Information
First Submitted Date  ICMJE August 25, 2021
First Posted Date  ICMJE August 31, 2021
Last Update Posted Date December 19, 2022
Actual Study Start Date  ICMJE August 5, 2022
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Relapsed Acute Myeloid Leukemia
  • Refractory Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: Lanraplenib
    Orally via tablets
    Other Name: LANRA
  • Drug: Gilteritinib
    Orally via tablets
    Other Name: XOSPATA®
Study Arms  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 25, 2021)
55
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2024
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Director of Clinical Operations 650-484-1583 clinicaltrials@kronosbio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05028751
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Current Responsible Party Kronos Bio
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Kronos Bio
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kronos Bio
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP