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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05028751
Recruitment Status : Recruiting
First Posted : August 31, 2021
Last Update Posted : November 22, 2022
Sponsor:
Information provided by (Responsible Party):
Kronos Bio

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).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Relapsed Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Drug: Lanraplenib Drug: Gilteritinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 5, 2022
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : October 2024


Arm Intervention/treatment
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.
Drug: Lanraplenib
Orally via tablets
Other Name: LANRA

Drug: Gilteritinib
Orally via tablets
Other Name: XOSPATA®

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.
Drug: Lanraplenib
Orally via tablets
Other Name: LANRA

Drug: Gilteritinib
Orally via tablets
Other Name: XOSPATA®




Primary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. Part 1: Maximally Tolerated Dose (MTD) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]
  4. 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) ]

Secondary Outcome Measures :
  1. Part 1: Maximal Plasma Concentration (Cmax) of Lanraplenib (LANRA) [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days) ]
  2. 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) ]
  3. 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) ]
  4. Part 1 and Part 2: Composite Complete Response (CR) Rate [ Time Frame: Up to 5 years ]
  5. Part 1 and Part 2: Composite Complete Response (CR) with Partial Hematologic Recovery (CRh) [ Time Frame: Up to 5 years ]
  6. Part 1 and Part 2: Duration of Response (DoR) [ Time Frame: Up to 5 years ]
  7. Part 1 and Part 2: Event Free Survival (EFS) [ Time Frame: Up to 5 years ]
  8. Part 1 and Part 2: Overall Survival (OS) [ Time Frame: Up to 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05028751


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

Locations
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United States, California
University of California Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 990095
Contact: Bruck Habtemariam    310-794-0242    bhabtemariam@mednet.ucla.edu   
United States, Georgia
The Blood and Marrow Transplant Group of Georgia Recruiting
Atlanta, Georgia, United States, 30342
Contact: Lawrence Morris, M.D.    404-255-1930    lemorris@bmtga.com   
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Anand Patel, M.D.    773-834-8206    anand.patel@uchospitals.edu   
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Eytan Stein, M.D.    212-639-3314    steine@mskcc.org   
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Ronan Swords, M.D.    503-494-9014    swords@ohsu.edu   
United States, Texas
Texas Oncology - Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Jonathan Huntzinger    469-783-1439    Jonathan.Huntzinger@usoncology.com   
United States, Wisconsin
Froedtert Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Althea Thomas, RN    414-805-2588    athomas@mcw.edu   
Sponsors and Collaborators
Kronos Bio
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Responsible Party: Kronos Bio
ClinicalTrials.gov Identifier: NCT05028751    
Other Study ID Numbers: KB-LANRA- 1001
2022-001279-15 ( EudraCT Number )
First Posted: August 31, 2021    Key Record Dates
Last Update Posted: November 22, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kronos Bio:
Acute Myeloid Leukemia
Lanraplenib
LANRA
Relapsed Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms