Administration of Gilteritinib to eliminate MRD in patients with AML and FLT3-ITD mutation.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hellenic Society Of Hematology

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-11-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Hellenic Society of Hematology

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of Gilteritinib treatment in eradication of measurable residual disease (MRD) by PCR-NGS for FLT3-ITD.

Conditions and MedDRA coding

Acute myeloid leukaemia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Patients must provide signed and dated informed consent for the study that has been approved by an Independent Ethics Committee (IEC) and the relevant Institution Review Board (IRB) of each participating centre, before performing any screening or study procedure.
2. Adult male or female patients.. Aged 18 – 75 years old on the day of signing informed consent.
3. Subjects must have a new diagnosis of primary/de novoFLT3-ITD mutated AML according to the WHO criteria (2017).
4. Body weight >40kg.
5. Subjects must be willing and able to comply with the relevant procedures, according to the protocol.
6. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of < 2 (See Appendix 1: ECOG Performance Status).
7. Subjects must have an estimated life expectancy of >3 months.
8. Female patients of childbearing potential: negative serum pregnancy test at the screening visit and negative urine pregnancy test within seven days prior to starting treatment with Gilteritib.
9. Female patients of reproductive potential must agree to use an effective method of contraception during treatment with Gilteritinib and for at least 6 months after stopping Gilteritinib.
10. Female patients of reproductive potential using hormonal contraceptives should add a barrier method of contraception.
11. Female subjects of child-bearing potential are eligible if they commit to contraception and if they are not pregnant, breastfeeding, nor considering becoming pregnant during the study or for at least 6 months after the last dose of Gilteritinib.
12. If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree, to use effective contraception during treatment and for at least 4 months after the last dose of Gilteritinib.
13. Subjects must be willing and able to return to the clinical site for adequate follow-up and to comply with the protocol as required.
14. Patients with positive MRD (by PCR-NGS for FLT3-ITD) after 2 cycles of intensive chemotherapy in combination with an FLT3- inhibitor will be eligible for enrolment.

Exclusion criteria 10

1. Subjects with secondary AML, including treatment-related [e.g., due to prior anthracycline use], as well as subjects with progression of antecedent hematological disorder [e.g., MDS, MPN or MDS/MPN ‘overlap’ syndrome].
2. Subjects with acute promyelocytic leukemia.
3. Subjects with a serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject participating in the clinical study (such as active/uncontrolled infection at the time of screening).
4. Subjects with a diagnosis of human immunodeficiency virus (HIV), active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection. Subjects with HBV inactive carrier status and/or HCV with low viral titres on antivirals (non-exclusionary medications) are eligible. Low viral hepatitis titre is defined per institutional guidelines.
5. Known hypersensitivity to the active substance or to any of the excipients of Gilteritinib.
6. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
7. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of Gilteritinib.
8. Patients not willing to comply with effective contraception.
9. Malabsorption syndrome or other condition that precludes oral route of administration.
10. History of clinically significant medical conditions or any other reason that the investigator determines would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The rate of FLT3-ITD MRD negativity after 2 cycles of treatment with Gilteritinib.

Secondary endpoints 6

1. Frequency and type of resistance mutations detected at relapse, with particular emphasis on the, RAS/MAPK pathway ( such as NRAS, KRAS, PTPN11, CBL, NF1).
2. Time to development of resistance (e.g., median duration of treatment before resistance is observed).
3. Phenotypic changes (via flow cytometry) associated with resistance. More specifically, phenotypes such as the CD34+CD38-CD123+ or the CD47, TIM-3, CD96 expression and the appearence/re-appearence of antigenic characterists will be evaluated.
4. Baseline biomarker profiles (gene expression, mutation profile, proteomics) correlated with treatment response. More specifically, the presence of co-mutations in DNMT3A, NPM1, TET2, ASXL1, TP53 and the expression of antiapoptotic genes (such as the BCL2 and the MCL1) will be evaluated.
5. Correlation between immune microenvironment features and response to treatment. More specifically, the expression of immunoregulatory molecules, such as the PD-L1, LAG-3, TIM-3 and the percentage of CD8+, T-regulatory and NK cells will be evaluated.
6. Predictive value of specific genomic or transcriptomic signatures for MRD negativity.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hellenic Society Of Hematology

Sponsor organisation

Hellenic Society Of Hematology

Address

Kifissias Leoforos 27

City

Athens

Postcode

115 23

Country

Greece

Scientific contact point

Organisation

Hellenic Society Of Hematology

Contact name

Giorgos Vasilopoulos

Public contact point

Organisation

Hellenic Society Of Hematology

Contact name

Giorgos Vasilopoulos

Third parties 2

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications