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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)

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

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

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

NCT ID

NCT05028751

First Posted

August 25, 2021

Last Updated

August 22, 2023

Sponsor

Kronos Bio

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

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

Arm Title

Part 2: Expansion Cohort

Arm Type

Experimental

Arm Description

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

montesinos_pau@gva.es

12. IPD Sharing Statement

Plan to Share IPD

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)

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