search
Back to results

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

Primary Purpose

Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Lanraplenib
Gilteritinib
Sponsored by
Kronos Bio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Lanraplenib, LANRA, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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
  • 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

Sites / Locations

  • University of California Los Angeles (UCLA)Recruiting
  • The Blood and Marrow Transplant Group of GeorgiaRecruiting
  • University of Chicago Medical CenterRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Oregon Health and Science UniversityRecruiting
  • Texas Oncology - Baylor Charles A. Sammons Cancer Center
  • University of Texas MD Anderson Cancer CenterRecruiting
  • Froedtert HospitalRecruiting
  • Hospital Universitario 12 de OctubreRecruiting
  • Hospital Germans Trias i PujolRecruiting
  • MD Anderson Cancer Center MadridRecruiting
  • Hospital Universitari Vall d'HebrónRecruiting
  • Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)Recruiting
  • Hospital Clínic de BarcelonaRecruiting
  • Hospital San Pedro de AlcantaraRecruiting
  • Hospital Universitario Fundación Jiménez DíazRecruiting
  • Hospital Universitari i Politècnic La Fe

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1: Dose Escalation

Part 2: Expansion Cohort

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Part 1 and Part 2: Number of Participants who Experience a Treatment-Emergent Adverse Event (TEAE)
Part 1 and Part 2: Number of Participants who Experience a Dose-Limiting Toxicity (DLT) for Lanraplenib (LANRA)
Part 1: Maximally Tolerated Dose (MTD) of Lanraplenib (LANRA)
Part 1: Recommended Phase 2 Dose (RP2D) of Lanraplenib (LANRA)

Secondary Outcome Measures

Part 1: Maximal Plasma Concentration (Cmax) of Lanraplenib (LANRA)
Part 1: Time to Maximal Plasma Concentration (Tmax) of Lanraplenib (LANRA)
Part 1: Area Under the Plasma Concentration x Time Curve from Hour 0 to the Last Measurable Time Point (AUC0-last) of Lanraplenib (LANRA)
Part 1 and Part 2: Composite Complete Response (CR) Rate
Part 1 and Part 2: Composite Complete Response (CR) with Partial Hematologic Recovery (CRh)
Part 1 and Part 2: Duration of Response (DoR)
Part 1 and Part 2: Event Free Survival (EFS)
Part 1 and Part 2: Overall Survival (OS)

Full Information

First Posted
August 25, 2021
Last Updated
August 22, 2023
Sponsor
Kronos Bio
search

1. Study Identification

Unique Protocol Identification Number
NCT05028751
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 5, 2022 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kronos Bio

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
Keywords
Acute Myeloid Leukemia, Lanraplenib, LANRA, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Dose Escalation
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2: Expansion Cohort
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lanraplenib
Other Intervention Name(s)
LANRA
Intervention Description
Orally via tablets
Intervention Type
Drug
Intervention Name(s)
Gilteritinib
Other Intervention Name(s)
XOSPATA®
Intervention Description
Orally via tablets
Primary Outcome Measure Information:
Title
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)
Title
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)
Title
Part 1: Maximally Tolerated Dose (MTD) of Lanraplenib (LANRA)
Time Frame
Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)
Title
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 Measure Information:
Title
Part 1: Maximal Plasma Concentration (Cmax) of Lanraplenib (LANRA)
Time Frame
Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)
Title
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)
Title
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)
Title
Part 1 and Part 2: Composite Complete Response (CR) Rate
Time Frame
Up to 5 years
Title
Part 1 and Part 2: Composite Complete Response (CR) with Partial Hematologic Recovery (CRh)
Time Frame
Up to 5 years
Title
Part 1 and Part 2: Duration of Response (DoR)
Time Frame
Up to 5 years
Title
Part 1 and Part 2: Event Free Survival (EFS)
Time Frame
Up to 5 years
Title
Part 1 and Part 2: Overall Survival (OS)
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Director of Clinical Operations
Phone
650-484-1583
Email
clinicaltrials@kronosbio.com
Facility Information:
Facility Name
University of California Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
990095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruck Habtemariam
Phone
310-794-0242
Email
bhabtemariam@mednet.ucla.edu
Facility Name
The Blood and Marrow Transplant Group of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lawrence Morris, M.D.
Phone
404-255-1930
Email
lemorris@bmtga.com
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anand Patel, M.D.
Phone
773-834-8206
Email
anand.patel@uchospitals.edu
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eytan Stein, M.D.
Phone
212-639-3314
Email
steine@mskcc.org
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ronan Swords, M.D.
Phone
503-494-9014
Email
swords@ohsu.edu
Facility Name
Texas Oncology - Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Completed
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naval G. Daver, MD
Phone
713-794-4392
Email
ndaver@mdanderson.org
Facility Name
Froedtert Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Althea Thomas, RN
Phone
414-805-2588
Email
athomas@mcw.edu
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
State/Province
Avenida De Córdoba Sin Número
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Maria Calbacho Robles
Phone
+34 913 908 678
Email
mcalbachorobles@gmail.com
Facility Name
Hospital Germans Trias i Pujol
City
Barcelona
State/Province
Badalona
ZIP/Postal Code
08916
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Susanna Vives
Phone
+34-93-497-8387
Facility Name
MD Anderson Cancer Center Madrid
City
Madrid
State/Province
Calle De Arturo Soria
ZIP/Postal Code
270
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Adolfo de la Fuente Burguera
Phone
+34 917 878 631
Email
afuente@mdanderson.es
Facility Name
Hospital Universitari Vall d'Hebrón
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dra. Montserrat Arnán
Phone
+34 932607750
Email
contactfortrialsICOLH@iconcologia.net
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
ZIP/Postal Code
170
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alejandro Pardines
Phone
+34 932275400
Ext
4353
Email
PARDINES@recerca.clinic.ca
Facility Name
Hospital San Pedro de Alcantara
City
Cáceres
ZIP/Postal Code
10001
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Miguel Bergua Burgues
Email
jmberguaburg@gmail.com
Facility Name
Hospital Universitario Fundación Jiménez Díaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Manuel Alonso Dominguez
Phone
+34 915 504 800
Ext
2673
Email
juan.adominguez@fjd.es
Facility Name
Hospital Universitari i Politècnic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Pau Montesinos Fernández
Phone
+34 96 1244925
Email
montesinos_pau@gva.es

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs