Clinical trial investigating the efficacy of gilteritinib and chemotherapy treatment in patients with Acute myeloid leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Gimema Franco Mandelli Onlus

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2025-07-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Fondazione GIMEMA Franco Mandelli Onlus · Astellas Pharma Europe Limitede

External identifiers

EU CT number

2024-518617-25-00

ClinicalTrials.gov

NCT06667973

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine efficacy and tolerability of Gilteritinib added in combination with chemotherapy in obtaining Complete Remission (CR + CRi + CRp) in newly diagnosed, non M3, FLT3-positive AML.

Secondary objectives 7

1. To describe duration of MRD-negative CR
2. To describe survival outcomes
3. To describe the feasibility of HSCT
4. To describe safety
5. To evaluate whole gene FLT3 mutations
6. To analyze MRD with next generation technologies (NGS)
7. To describe quality of life

Conditions and MedDRA coding

newly diagnosed non-M3 FLT3-positive acute myeloid leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. The patient is ≥ 18 and ≤65 years old.
2. The patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 to 2.
3. The patient has adequate baseline organ function, including cardiac, renal, and hepatic function:a. Left ventricular ejection fraction (LVEF) ≥institutional lower limit of normal as measured by multigated acquisition (MUGA) scan or 2-dimensional (2-D) echocardiography (ECHO) within 21 days before start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG). b. ECG: QTcF≤450 male ≤480 female c. Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation. d. Bilirubin ≤3 times the upper limit of normal ULN mg/dL except for Gilbert’s condition e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)., except if due to leukemic involvement.
4. Patient is positive at diagnosis for FLT3 activating mutation in bone marrow or whole blood.
5. Diagnosis of untreated AML according to WHO 2016, non-APL.
6. If the patient is a woman of childbearing potential (WOCBP), she must have a negative serum or urine pregnancy test at screening within 1 week before treatment.
7. The patient (male and female) agrees to use two acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for 6 months after the end of treatment
8. The patient has signed informed consent before initiation of any study-specific procedures or treatment.
9. The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.

Exclusion criteria 12

1. Patient was diagnosed as acute promyelocytic leukemia.
2. Patient has BCR-ABL-positive leukemia or chronic myelogenous leukemia in blast crisis.
3. Patient has clinically active central nervous system leukemia.
4. Patient has been diagnosed with another malignancy, unless disease-free for at least 3 years. Subjects with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, papillary thyroid carcinoma, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Subjects with organconfined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
5. Patient has had major surgery within 4 weeks prior to the first study dose.
6. Patient has radiation therapy within 4 weeks prior to the first study dose.
7. Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 1 month prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
8. Patient has an active uncontrolled infection.
9. Patient has active human immunodeficiency virus infection.
10. Patient has active hepatitis B or C or other active hepatic disorder. Chronic conditions previously cured or in active prophylaxis are allowed in the study
11. Patient has infections, comorbidities or any disease, condition or alteration that per judgment of the investigator may be jeopardized by therapy
12. Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy with the exception of Hydroxyurea (HU) or 6- Mercaptopurine (6MP) in patients who need to continue this agent to maintain WBC count ≤10,000/mm3. HU and 6MP must be discontinued at the time of initiation of study medications.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary end point is the rate of CR after course 1 or course 2 if course 2 is administered (CR + CRi + CRp).

Secondary endpoints 10

1. Percentage of MRD negative CR (flow cytometry) after cycle 1, 2, consolidation, End of Treatment and follow-up (centralized analysis).
2. To Describe duration of MRD negative CR measured as the time from achievement of MRD negative CR to MRD positive test, relapse or death for any cause.
3. To Describe PFS, measured as the time from 1st day of administration of study treatment to progression or death for any cause.
4. To Describe OS, measured as the time from 1st day of administration of study treatment to death for any cause.
5. To Describe the proportion of patients who proceed to HSCT in MRD negative CR.
6. To Describe the incidence of AE.
7. To Analyze incidence and type of whole gene FLT3 mutations.
8. To Analyze the overlap between conventional MRD and MRD with next generation technologies (NGS) for correlative purposes.
9. To Describe adherence to treatment.
10. To Describe quality of life.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Gimema Franco Mandelli Onlus

Sponsor organisation

Fondazione Gimema Franco Mandelli Onlus

Address

Via Casilina 5

City

Rome

Postcode

00182

Country

Italy

Scientific contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

Data center

Public contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

Data center

Third parties 4

Locations

1 EU/EEA country · 22 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 9 files

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

Application history

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