Efficacy of Gilteritinib in Combination With FLAI as Induction Therapy of FLT3-positive Acute Myeloid Leukemia

NCT06667973 | Not Yet Recruiting Phase 2

• 1 other identifier: AML2924
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate the efficacy of gilteritinib as induction therapy in FLT3-positive adult acute myeloid leukemia patients. The main question it aims to answer is: Is gilteritinib in combination to chemotherapy able to improve the complete remission rate of FLT3-positive AML? Participants will receive up to 2 induction cycles with gilteritinib in combination with FLAI (fludarabine, cytarabine, idarubicine) and up to 3 consolidation cycles with gilteritinib and high-dose cytarabine.

Conditions

Acute Myeloid Leukemia; FLT3 Gene Mutation; Adult AML; Diagnosis

Outcome Measures

Primary Outcomes (1)

• Complete remission rate after induction

  Number of patients who achieve a CR after course 1 or course 2 if adiministered on the total of evaluable patients

  2 months

Study Arms (1)

Newly-diagnosed FLT3-positive Acute Myeloid Leukemia treated with gilteritinib

EXPERIMENTAL

Treatment consists in up to 2 induction cycles and up to 3 consolidation cycles: Induction: Patients will receive Gilteritinib 120 mg QD p.o from day 6 to 26 (21 days), in combination with FLAI induction (fludarabine 30 mg/sqm from day 1 to 5, cytarabine 2000 mg/sqm from day 1 to 5, Idarubicine 10 mg/sqm on days 1, 3, 53). Response will be assessed on day 28 with a bone marrow aspirate. * In patients not achieving CR, the second induction cycle will be identical to Induction I. * In patients achieving CR, a second induction cycle with ARA-C + IDA will be allowed (cytarabine 2000 mg/sqm from day 1 to 5, Idarubicine 10 mg/sqm on days 1, 3, 5), with the same schedule for Gilteritinib (day 6 to 26) Up to 3 consolidation cycles consisting in high dose cytarabine (1500-3000 mg/sqm bid on days 1,3,5) or intermediate in combination with Gilteritinib 120 mg QD p.o from day 6 to 26 will be allowed. Patients considered eligible may proceed to allo-HSCT at any time after day 28.

Drug: Gilteritinib

Interventions

Gilteritinib DRUG

Gilteritinib fumarate is an oral, selective FLT3 and AXL inhibitor. It is a type 1 inhibitor, active against both the FLT3-ITD and FLT3-TKD mutations. Gilteritinib inhibits FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, FLT3-D835Y, and FLT3-ITD-D835Y, and it induces apoptosis in leukemic cells expressing FLT3-ITD. Gilteritinib is approved for the treatment of relpased/refractory FLT3-mutated AML after the successfull ADMIRAL trial. In the present study Gilteritinib (120 mg/die) in combination with FLAI will be tested as induction therapy in newly-diagnosed patients.

Newly-diagnosed FLT3-positive Acute Myeloid Leukemia treated with gilteritinib

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient is ≥ 18 and ≤65 years old.
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 to 2.
• The patient has adequate baseline organ function, including cardiac, renal, and hepatic function:
• 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).
• ECG: QTcF≤450 male ≤480 female
• 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.
• Bilirubin ≤3 times the upper limit of normal ULN mg/dL except for Gilbert's condition
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)., except if due to leukemic involvement.
• Patient is positive at diagnosis for FLT3 activating mutation in bone marrow or whole blood.
• Diagnosis of untreated AML according to WHO 2016, non-APL
• 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.
• 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
• The patient has signed informed consent before initiation of any study-specific procedures or treatment.
• The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment

You may not qualify if:

• Patient was diagnosed as acute promyelocytic leukemia.
• Patient has BCR-ABL-positive leukemia or chronic myelogenous leukemia in blast crisis.
• Patient has clinically active central nervous system leukemia.
• 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 organ-confined 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.
• Patient has had major surgery within 4 weeks prior to the first study dose.
• Patient has radiation therapy within 4 weeks prior to the first study dose.
• 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%.
• Patient has an active uncontrolled infection.
• Patient has active human immunodeficiency virus infection.
• 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
• Patient has infections, comorbidities or any disease, condition or alteration that per judgment of the investigator may be jeopardized by therapy
• 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.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Disease

Interventions

gilteritinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Fabio Guolo

  IRCCS Policlinico San Martino, UO Clinica Ematologica - Genova

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paola Fazi

CONTACT

0670390528; p.fazi@gimema.it

Enrico Crea

CONTACT

0670390514; e.crea@gimema.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: October 31, 2024
• Study Start: June 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): June 1, 2030
• Last Updated: March 12, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share