AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1/2NCT05028751

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

A Phase 1/2 study testing Lanraplenib and Gilteritinib in people with Acute Myeloid Leukemia and Relapsed Acute Myeloid Leukemia, run by Kronos Bio at 17 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lanraplenib and Gilteritinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
17 sitesin 2 countries
Study dates
5 Aug 2022to 9 Apr 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 14Show fewer
  • 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 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, or portal hypertension
  • Ongoing (within 6 weeks of study enrollment) hepatic encephalopathy
  • Ongoing immunosuppressive therapy, including systemic chemotherapy for treatment of leukemia

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

Spain9 sites

  • Hospital Germans Trias i Pujol

    Barcelona, Badalona, 08916

  • Hospital Universitari Vall d'Hebrón

    Barcelona, 08035

  • Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

    Barcelona, 08908

  • Hospital Clínic de Barcelona

    Barcelona, 170

  • Hospital San Pedro de Alcantara

    Cáceres, 10001

  • Hospital Universitario 12 de Octubre

    Madrid, Avenida de Córdoba Sin Número, 28041

  • MD Anderson Cancer Center Madrid

    Madrid, Calle de Arturo Soria, 270

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026

Other trials in Spain

United States8 sites

  • The Blood and Marrow Transplant Group of Georgia

    Atlanta, Georgia, 30342

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Texas Oncology - Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California Los Angeles (UCLA)

    Los Angeles, California, 990095

  • Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Oregon Health and Science University

    Portland, Oregon, 97239

Other trials in United States

About this study

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

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).

Being tested
Lanraplenib, Gilteritinib
Keywords
Acute Myeloid Leukemia, Lanraplenib, LANRA, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LanraplenibDrug

    Also called LANRA

    Orally via tablets

  • GilteritinibDrug

    Also called XOSPATA®

    Orally via tablets

Study groups in NCT05028751
Study groupRoleWhat they receive
LANRA 20 mg QD + Gilteritinib 120 mg QDExperimentalParticipants received LANRA 20 mg once daily (QD) as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 1. Participants also received gilteritinib 120 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 2. Participants received treatment until progression/relapse or lack of at least a partial remission (PR) after 6 months of study treatment, intolerance, or withdrawal from treatment by the participant or study investigator.
Receives: Drug: Lanraplenib; Drug: Gilteritinib
LANRA 40 mg QD + Gilteritinib 120 mg QDExperimentalParticipants received LANRA 40 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 1. Participants also received gilteritinib 120 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 2. Participants received treatment until progression/relapse or lack of at least a PR after 6 months of study treatment, intolerance, or withdrawal from treatment by the participant or study investigator.
Receives: Drug: Lanraplenib; Drug: Gilteritinib
LANRA 60 mg QD + Gilteritinib 120 mg QDExperimentalParticipants received LANRA 60 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 1. Participants also received gilteritinib 120 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 2. Participants received treatment until progression/relapse or lack of at least a PR after 6 months of study treatment, intolerance, or withdrawal from treatment by the participant or study investigator.
Receives: Drug: Lanraplenib; Drug: Gilteritinib
LANRA 90 mg QD + Gilteritinib 120 mg QDExperimentalParticipants received LANRA 90 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 1. Participants also received gilteritinib 120 mg QD as oral tablets in consecutive 28-day cycles starting from Cycle 1 Day 2. Participants received treatment until progression/relapse or lack of at least a PR after 6 months of study treatment, intolerance, or withdrawal from treatment by the participant or study investigator.
Receives: Drug: Lanraplenib; Drug: Gilteritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

    A TEAE was any unfavorable or unintended sign, symptom, laboratory abnormality or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered causally related to the study drug or not that started after the first dose of the earliest study drug through the lesser of non-protocol anti-leukemic therapy initiation or end of treatment visit.

    A serious TEAE was defined as any TEAE that:

    • Resulted in death.
    • Was life-threatening.
    • Required or prolonged a pre-existing hospitalization.
    • Resulted in disability/incapacity.
    • Was a congenital anomaly/birth defect.
    • Was considered a significant medical event by the investigator.

    TEAEs were graded for severity based on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 as follows:

    • Grade 1 - Mild.
    • Grade 2 - Moderate.
    • Grade 3 - Severe.
    • Grade 4 - Life-threatening.
    • Grade 5 - Death related to adverse event (AE).

    Measured: Cycle 1 Day 1 (each cycle was 28 days) to 30 days after last dose of either LANRA or gilteritinib or initiation of non-protocol antileukemic therapy, whichever was earlier (maximum duration of treatment was 183 days)

  2. Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) for LANRA

    A DLT was defined as any of the following occurring within the DLT assessment period:

    • A nonhematologic toxicity of Grade ≥ 3 that was at least possibly related to LANRA (with noted exceptions).
    • Any toxicity that resulted in administration of < 80% of the cumulative, Cycle 1 dose for either LANRA or gilteritinib.
    • Grade 4 neutropenia or thrombocytopenia lasting > 28 days after treatment onset that was not attributed to active acute myeloid leukemia (AML) and was at least possibly related to LANRA.
    • Any toxicity that resulted in reduction in the dose of LANRA in Cycle 1.

    DLTs were graded for severity based on the NCI-CTCAE version 5.0 as follows:

    • Grade 3 - Severe.
    • Grade 4 - Life-threatening.

    Measured: Cycle 1 Day 1 to pre-dose Cycle 2 Day 1 (each cycle was 28 days)

  3. Maximally Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of LANRA in Combination With Standard Doses of Gilteritinib

    The MTD/RP2D was defined as the highest dose with either 0 of 3 or no more than 1 of 6 patients with LANRA-related DLTs. All decisions regarding dose escalation including declaration of the MTD/RP2D were made by the dose-escalation committee (DEC).

    Measured: Cycle 1 Day 1 to pre-dose Cycle 2 Day 1 (each cycle was 28 days)

Secondary outcomes (10)

  1. Maximal Plasma Concentration (Cmax) of LANRA

    Cmax was derived from plasma concentrations of LANRA using standard non-compartmental methods and actual sample times.

    Measured: Cycle 1 Day 1 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose.

  2. Time to Cmax (Tmax) of LANRA

    Tmax was derived from plasma concentrations of LANRA using standard non-compartmental methods and actual sample times.

    Measured: Cycle 1 Day 1 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose.

  3. Area of the Plasma Concentration x Time Curve From Hour 0 to the Last Measurable Time Point (AUC0-last) of LANRA

    AUC0-last was derived from plasma concentrations of LANRA using standard non-compartmental methods and actual sample times.

    Measured: Cycle 1 Day 1 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose.

  4. Cmax of Gilteritinib

    Cmax was derived from plasma concentrations of gilteritinib using standard non-compartmental methods and actual sample times.

    Measured: Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose.

  5. Tmax of Gilteritinib

    Tmax was derived from plasma concentrations of gilteritinib using standard non-compartmental methods and actual sample times.

    Measured: Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose.

  6. AUC0-last of Gilteritinib

    AUC0-last was derived from plasma concentrations of gilteritinib using standard non-compartmental methods and actual sample times.

    Measured: Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose.

  7. Composite Complete Remission (cCR) Rate Per European LeukemiaNet (ELN) 2017 Criteria

    Percentage of participants with cCR included CR and CR with partial hematologic recovery (CRh).

    CR required all of the following, per ELN 2017 criteria:

    • Bone marrow blasts < 5 %.
    • Absence of circulating blasts and blasts with Auer rods.
    • Absence of extramedullary disease (ie, leukemia outside of bone marrow confirmed by biopsy).
    • Absolute neutrophil count > 1.0 x 10^9/L (1,000/μL).
    • Platelet count >100 x 10^9/L (100,000/μL).

    CRh required all aforementioned CR criteria except for the below:

    • Absolute neutrophil count > 0.5 x 10^9/L (500/μL) and/or;
    • Platelet count > 50 x 10^9/L (50,000/μL).

    Measured: Cycle 1 Day 1 until occurrence of documented CR or CRh (maximum duration of follow-up was 16.1 months).

  8. Duration of Response (DOR)

    DOR was defined as the time from first qualifying response (CR/CRh) until relapse or death from any cause, as assessed by study investigators.

    CR required all of the following:

    • Bone marrow blasts < 5 %.
    • Absence of circulating blasts and blasts with Auer rods.
    • Absence of extramedullary disease (ie, leukemia outside of bone marrow confirmed by biopsy).
    • Absolute neutrophil count > 1.0 x 10^9/L (1,000/μL).
    • Platelet count >100 x 10^9/L (100,000/μL).

    CRh required all aforementioned CR criteria except for the below:

    • Absolute neutrophil count > 0.5 x 10^9/L (500/μL) and/or;
    • Platelet count > 50 x 10^9/L (50,000/μL).

    Relapse was defined as the reappearance of circulating blasts or ≥ 5% blasts in the bone marrow not attributable to any other cause or reappearance of cytologically or biopsy documented extramedullary disease.

    Measured: From first qualifying response (CR/CRh) until relapse or death from any cause (maximum duration of follow-up was 16.1 months).

  9. Event-free Survival (EFS)

    EFS was defined as the time from treatment onset until treatment failure (ie, failure to achieve CR/CRh, relapse from CR/CRh, or death from any cause).

    CR required all of the following:

    • Bone marrow blasts < 5 %.
    • Absence of circulating blasts and blasts with Auer rods.
    • Absence of extramedullary disease (ie, leukemia outside of bone marrow confirmed by biopsy).
    • Absolute neutrophil count > 1.0 x 10^9/L (1,000/μL).
    • Platelet count >100 x 10^9/L (100,000/μL).

    CRh required all aforementioned CR criteria except for the below:

    • Absolute neutrophil count > 0.5 x 10^9/L (500/μL) and/or;
    • Platelet count > 50 x 10^9/L (50,000/μL).

    Relapse was defined as the reappearance of circulating blasts or ≥ 5% blasts in the bone marrow not attributable to any other cause or reappearance of cytologically or biopsy documented extramedullary disease.

    Measured: Cycle 1 Day 1 to treatment failure (ie, failure to achieve CR or CRh, relapse from CR/CRh or death from any cause) (maximum duration of follow-up was 16.1 months).

  10. Overall Survival

    Overall survival was defined as the time from enrollment until death from any cause. Overall survival was estimated using Kaplan-Meier methodology.

    Measured: Enrollment until death from any cause (maximum duration of follow-up was 16.1 months).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2021
  2. Study start5 Aug 2022
  3. Primary completion9 Apr 2024
  4. Study completion9 Apr 2024

Why it stopped: Sponsor decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05028751
Sponsor's protocol ID
KB-LANRA- 1001
Other IDs
2022-001279-15
Status last verified
Jul 2024
First submitted
25 Aug 2021
Last updated
7 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lanraplenib and Gilteritinib in people with Acute Myeloid Leukemia and Relapsed Acute Myeloid Leukemia, run by Kronos Bio at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Spain, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) (time frame: Cycle 1 Day 1 (each cycle was 28 days) to 30 days after last dose of either LANRA or gilteritinib or initiation of non-protocol antileukemic therapy, whichever was earlier (maximum duration of treatment was 183 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05028751.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2024; AzTrials last refreshed its copy on 1 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in