Pediatric study of Gilteritinib in FLT3 positive R/R AML
Research type
Research Study
Full title
A Phase 1/2, Multicenter, Open-Label, Single Arm, Dose Escalation and Expansion Study of Gilteritinib (ASP2215) Combined with Chemotherapy in Children, Adolescents and Young Adults with FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
IRAS ID
270337
Contact name
Alice Norton
Contact email
Sponsor organisation
Astellas Pharma Global Development, Inc. (APGD)
Eudract number
2018-002301-61
Clinicaltrials.gov Identifier
IND Number, 117548
Duration of Study in the UK
6 years, 2 months, 10 days
Research summary
Research Summary
Acute Myeloid Leukaemia (AML) is a group of biologically heterogeneous (diverse) diseases that comprise 20% of paediatric and 80% of acute leukaemia. Mutations in FMS-like tyrosine kinase 3 (FLT3) called a FLT3 ITD mutation is one of the most common genetic alterations in AML and are associated with high rates of relapse in adults and children. When patients have a FLT3 ITD mutation, more of the FLT3 protein is on the leukemic cells, or the protein is more active. This may make the leukemic cells grow faster or live longer.
The investigational study drug Gilteritinib is a cancer drug that acts as an inhibitor of FLT3.The goal of the study is to test if Gilteritinib given in combination with FLAG chemotherapy (regime used for relapsed and refractory AML) is effective and safe treatment in children, adolescents and young adults with relapsed-refractory AML with mutations in the FLT3 gene.
The study will be divided in two phases (Treatment Period), phase 1 will be to learn the best and safest dose of Gilteritinib and phase 2 will be to learn if the best dose selected in Phase 1 is safe, works in treating AML and how it affects the body. Once the Treatment Period is completed participants will have the option to proceed with Long Term Treatment Period, which allows participants to receive treatment with Gilteritinib for up to 2 years. The Treatment Period of the study (phase 1 or 2) will take about 2 months. The Long Term Treatment Period can last up to 2 years.
This study will involve up to 114 participants from 6 months to less than 21 years of age from approximately 30 sites in North America, Europe and Asia.
The sponsor of this study is Astellas Pharma Global Development, Inc. (APGD).
Summary of Results
CLINICAL STUDY RESULTS A study of Gilteritinib combined with chemotherapy in children, adolescents and young adults with FMS like tyrosine kinase 3 (FLT3)/internal tandem duplication (ITD) positive relapsed or refractory acute myeloid leukemia (AML)
Thank you!
Astellas is grateful to children and adolescents for taking part in this clinical study, and to their families and caregivers. We think it’s important that you, your child and the general public know the results of clinical studies.
Astellas reviewed all the study information and created a report of the results. This is a summary of that report.Overall Summary:
In this study, researchers wanted to learn if gilteritinib, given in combination with FLAG chemotherapy, was safe in children, adolescents and young adults with relapsed or refractory acute myeloid leukemia (AML) with faulty FLT3 gene. FLAG is a combination of 3 chemotherapy medicines used to treat people with relapsed or refractory AML. The researchers also looked for the most suitable dose. Gilteritinib 2 mg/kg/day was found to be the most suitable dose for participants 2 years to less than 18 years of age. Out of 9 participants, 6 showed no symptoms of AML after receiving up to 2 cycles of treatment. Gilteritinib was well tolerated by the children and adolescents, and no new safety issues were reported in this study. Because the study stopped early, too few participants joined the study for the researchers to draw conclusions from the results.Acute myeloid leukemia, or AML for short, is a type of cancer in which bone marrow makes too many abnormal white blood cells. These are called leukemia cells. Some people with AML have a faulty FLT3 gene which causes leukemia cells to grow faster. The word acute means the cancer can get worse quickly. Bone marrow is the soft part inside bones where new healthy blood cells are made.
Gilteritinib is an approved treatment for adults with AML with faulty FLT3 gene who haven’t responded to previous treatment (refractory), or whose cancer came back after previous treatment (relapsed).
In this study, researchers gave gilteritinib to children for the first time. Researchers were looking to find the most suitable dose of gilteritinib to be used safely together with FLAG chemotherapy in children, adolescents and young adults with relapsed or refractory AML with faulty FLT3 gene. Chemotherapy uses medicines to kill cancer cells or stop them from growing and dividing. FLAG is a combination of 3 medicines used to treat people with relapsed and refractory AML. It has fludarabine, cytarabine and granulocyte colony stimulating factor (G CSF) in it.
The study started in September 2020. The sponsor stopped the study in March 2025. This happened because not enough participants joined the study since it is a rare medical condition in children. It was not due to any safety concerns.In this summary, study treatment means the treatment given to the participants during the study.
In this study, the study treatments were gilteritinib and FLAG chemotherapy.
Gilteritinib was taken as tablets. Fludarabine and cytarabine were given as an infusion into a vein and G-CSF was given as an infusion into a vein or injection directly under the skin.
Participants received 2 mg of gilteritinib per kilogram of bodyweight per day; any participant weighing 60 kg or more received 120 mg/day.The study was planned to have 2 parts:
Part 1: The participants were divided into 3 age groups. A small number of participants in each group were to be given low to high doses of gilteritinib to find the most suitable dose to use in Part 2. To find the most suitable dose, researchers looked for “dose-limiting toxicities or DLTs”. DLTs are side effects of the study treatment that are serious enough to prevent an increase in the dose of the study treatment.
Part 2: Researchers planned to give the most suitable dose of gilteritinib identified in Part 1 to different participants in order to learn how well gilteritinib works.
Part 2 of the study did not happen. The sponsor stopped the study after the first group of participants in Part 1 completed the study. This was because not enough participants joined the study since it is a rare medical condition in children. The decision was not due to safety concerns.Children and adolescents with faulty FLT3 gene and having relapsed or refractory AML took part in this study. The participants in this study were 8 to 15 years old when they joined. This study included 6 males and 3 females (9 participants in total) in 5 countries.
The number of medical centers with the number of participants who joined the study in each country is shown below:
Country (Number of Centers) Number of Participants
Germany (1) 2
Italy (1) 2
Spain (1) 1
United Kingdom (2) 3
United States (1) 1Before participants could join the study and get study treatments, the study doctors made sure they could take part in this study (met all the study rules).
Study-Part 1: Participants in Part 1 were to be divided into 3 groups depending on their age.
• Group 1: aged 2 years to less than 21 years
• Group 2: aged 1 year to less than 2 years
• Group 3: aged 6 months to less than 1 yearThe study design below shows what happened during Part 1 of the study.
Both Group 2 and Group 3 were opened for participants to join. However, no participants joined Group 2 and 3 and the sponsor decided to stop the study.
After the study treatment ended, participants in Group 1 returned to the hospital for regular health checks. Study doctors contacted participants once every 3 months for up to 2 years to ask about their cancer and overall health.• What was the most suitable dose of gilteritinib that participants could tolerate?
• How many participants showed no symptoms of AML after receiving up to 2 cycles of gilteritinib together with FLAG chemotherapy?The results presented in this summary are from this study only.
What was the most suitable dose of gilteritinib that participants could tolerate?
In Part 1 of the study, only 8 participants had available results when checking for the most suitable dose of gilteritinib.
Researchers found gilteritinib at 2 mg/kg/day to be the most suitable dose for participants between 2 years to less than 18 years of age. No DLTs were observed in these participants.How many participants showed no symptoms of AML after receiving up to 2 cycles of gilteritinib together with FLAG chemotherapy?
Out of 9 participants, 6 (66.7%) showed no symptoms of AML after receiving up to 2 cycles of treatment.
Because the study stopped early, too few participants joined the study for the researchers to draw conclusions from the results.Much research is needed to know whether a treatment causes a medical problem. When new treatments are being studied, researchers keep track of all medical problems that people have while they are in the study. These problems are called adverse events and are recorded whether or not they might be caused by the study treatment received.
An adverse event that the study doctor thinks might have been caused by a study treatment during this study is called an adverse reaction. This summary provides information on the adverse reactions recorded during this study only. These were recorded up to 28 days after the last dose of study treatment. Other studies may record different adverse reactions.
An adverse reaction is considered serious when it is fatal, life-threatening, causes lasting problems or needs hospital care.Did participants have any adverse reactions during this study?
A summary of how many participants had adverse reactions to the study treatments during the study is shown here:
Adverse reactions Gilteritinib 2 mg/kg/day
(out of 9 participants)
How many participants had adverse reactions? 9 (100%)
How many participants stopped taking study treatment because of adverse reactions? 1 (11.1%)
How many participants had serious adverse reactions? 4 (44.4%)What adverse reactions did participants have during the study?
In this study, common means at least 30 in 100 (30%) or more participants had adverse reactions.
A summary of how many participants had common adverse reactions to the study treatment during the study is shown here:
Adverse reaction Gilteritinib 2 mg/kg/day
(out of 9 participants)
Increase in liver test value of ALT in the blood (Alanine aminotransferase increased). This may be a sign of liver problem. 6 (66.7%)
Increase in liver test value of AST in the blood (Aspartate aminotransferase increased). This may be a sign of liver problem. 5 (55.6%)
Desire to vomit (Nausea) 4 (44.4%)
Vomiting 4 (44.4%)
Low number of red blood cells (Anaemia) 3 (33.3%) Fever (Pyrexia) 3 (33.3%)
What serious adverse reactions did participants have during the study?
A summary of how many participants had serious adverse reactions to the study treatment during the study is shown here:
Serious adverse reaction Gilteritinib 2 mg/kg/day
(out of 9 participants)
Increase in liver test value of ALT in the blood (Alanine aminotransferase increased). This may be a sign of liver problem. 1 (11.1%)
Increase in liver test value of AST in the blood (Aspartate aminotransferase increased). This may be a sign of liver problem. 1 (11.1%)
Increase in liver test value of bilirubin (Blood bilirubin increased) 1 (11.1%)
Joint pain (Arthralgia) 1 (11.1%)
Fever (Pyrexia) 1 (11.1%)
Fever in patients with low neutrophils (Febrile neutropenia). Neutrophils are white blood cells that protect from infection. 1 (11.1%)
Increase in white blood cell count (White blood cell count increased) 1 (11.1%)4 participants passed away during the study. None of the deaths were thought to be caused by gilteritinib.
Clinical studies help researchers and health authorities answer research questions to help decide on new treatments. This study helped researchers learn how well gilteritinib works in children, adolescents and young adults with FLT3 positive relapsed or refractory AML.
Other studies may provide new or different results. Researchers review the results of many studies before they decide on a new treatment. When this summary was written, other studies with gilteritinib in children and adolescents were still in progress and might have shown different results.
If you have any questions about the results for this study, please speak with your study doctor or staff at your study clinic.When was the study done? From September 2020 until March 2025
More information about the study is shown here:
Study Title A Phase 1/2, Multicenter, Open-Label, Single Arm, Dose Escalation and Expansion Study of Gilteritinib (ASP2215) Combined with Chemotherapy in Children, Adolescents and Young Adults with FMS like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study Number 2215-cl-0603
ClinicalTrials.gov
(US number) NCT04240002
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https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.clinicaltrials.astellas.com%252F%2FNBTI%2FemjAAQ%2FAQ%2Fe6874946-251c-4ed6-9cb6-9bb6ff00aa94%2F3%2FjAOspO59-9&data=05%7C02%7Cedgbaston.rec%40hra.nhs.uk%7C656f1d93257748aac25208de00ec5c99%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638949212350407754%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=swkA8e6cqgIpVzkm3nSvFMwZYbQnNn7QuIMcdI5xW78%3D&reserved=0This summary was completed by Astellas in July 2025.
Thank you for taking part in this important research!
REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
19/WM/0338
Date of REC Opinion
14 Jan 2020
REC opinion
Further Information Favourable Opinion