Open label, multicenter study of gilteritinib in sequential treatment with MEC (Mitoxantrone/ Etoposide/ Cytarabine) in patients with relapsed or refractory FLT3-mutated Acute Myeloid Leukemia

JRCT ID: jRCTs041200067

Registered date:20/11/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: relapsed/refratory FLT3-mutated acute myeloid leukemia
• Date of first enrollment: 09/12/2020
• Target sample size: 42
• Study type: Interventional

Intervention(s)

Induction therapy (cycle1 28 days)
Mitoxantrone 8 mg/m2 intravenous infusion for over 30 minutes, day 1 - 3
Etoposide 100 mg/m2 intravenous infusion for over 3 hours, day 1 - 5
Cytarabine 100 mg/m2 continuous intravenous infusion for 24 hours, day 1 - 7
Gilteritinib 120 mg orally day 8 - 28

Maintenance therapy (cycle 2 - 13, 28 days x 12 cycles)
Gilteritinib 120 mg orally day 1 - 28

Outcome(s)

• Primary Outcome: Complete remission (CR) rate during treatment

Secondary Outcome

Adverse events,
VAF measurements (FLT3-ITD, FLT3-TKD, NPM1),
CR rates before hematopoietic cell transplantation,
CR with incomplete hematologic recovery (CRh),
CR/CRh,
CRc,
Overall response rates (ORR; CRc+PR),
Time to achieve CR, CRc, overall response,
Duration of CR, CRc, overall response,
Overall survival (OS),
Relapse-free survival (RFS),
Rates of transfusion independence,
Persistence of transfusion independence,
Duration of hospitalization
ECOG PS,

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Acute myeloid leukemia (AML) diagnosed according to WHO 2016 criteria,
2. Relapsed or refractory, FLT3-mutated AML (FLT3 mutation should be proven by using an approved detection kit. Patients who were enrolled in JALSG CS 17-molecular study and found to hold FLT3 mutation are to be enrolled in this study. Patients who relaped after hematopoetic cell transplantation are eligible.
3. Written informed consent obtained,
4. Male or female patients 20 years or older,
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0,1,2,
6. Hepatic, renal, pulmonary, and cardiac functions that are torelable to the treatment, as follows.
1, Total bilirubin <= 2.0 mg/dL,
2, Serum creatinine <= 2.0 mg/dL,
3, PaO2 >= 60 Torr or SPO2 >= 90% (room air),
4, Cardiac function detailed in Exclusion Criteria below,
7. Pateints who agree not to participate in other intervention clinical trials,
8. Male patients should agree to practice effective barrier contraception during the entire study period and a certain period (120 days) after the last dose of the study drug.
9. Female patients should agree to practice one highy effective method of contraception during the entire study period and a certain period (180 days) after the last dose of the study drug.

Exclude criteria

1. Acute promyelocytic leukemia (APL),
2. BCR-ABL1-positive leukemia (blastic crisis of chronic myeloid leukemia),
3. Active malignant diseases other than AML or myelodysplastic syndromes (MDS), except for those in remission for 2 years or longer,
4. Clinically acitve CNS leukemia,
5. Major operation performed within 28 days of the drug adminisitration,
6. New York Heart Association (NYHA) 3 or 4, or chronic heart failure, or past history of chronic heart failure,
7. Cardiac dysfunction or clinically important heart diseases, as follows,
Complete AV block,
QT elongation (QTcF > 450 msec),
Arrhythmias without correct QT interrnal measurement,
Right bundle branch block + left anterior hemiblock (two bundle blocks),
New onset angina pectoris within 3 months prior to the initiation of the drug administration,
New onset acute mylocardial infarction within 3 months prior to the initiation of the drug administration,
Pace maker dependency,
Ventricular or atrial tachyarrhythmias uncontrollable by medication,
LVEF < 50% in patients showing any abnormalities by electrocardiogam,
8. Cumulative maximum anthracycline doses (doxorubicin =>430 mg/m2),
9. Pregnant women,
10. Breast-feeding women,
11. Active, uncontrollable infectious diseases,
12. Active hepatitis B, C, (Inactive carrier is allowed),
13. Human immunodificiency virus (HIV) infection,
14.COVID-19 infection,
15. Any patients whom attending physicians request to be withdrawn from the study,
16. Past histories of hypersensitivity or allergic reactions to the ingradients of the study drugs.

Related Information

• Primary Sponsor: Yamauchi Takahiro
• Source(s) of Monetary Support: Astellas Pharma Inc.