Acute myeloid leukemia MedDRA version: 20.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Quizartinib
Product Code: AC220
Pharmaceutical Form: Tablet
INN or Proposed INN: Quizartinib
CAS Number: 950769-58-1
Sponsors
FUNDACIÓN PETHEMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent before the first screening procedure. The patient and the investigator must sign informed consent form. 2. Diagnosis of untreated AML (according to the WHO 2008/2016 definition) 3. Age = 18 and =70 years old at the time of screening 4. Non-FLT3-ITD (allelic ratio =65 years) yes F.1.3.1 Number of subjects for this age range 281
Exclusion criteria
Exclusion criteria: 1. Patients with a genetic diagnosis of acute promyelocytic leukemia 2. Age 70 years 3. ECOG performance status of 3 or 4 4. Prior treatment for AML, except for the following allowances: a) Leukapheresis b) Treatment for hyperleukocytosis with hydroxyurea 5. Blastic phase of bcr/abl chronic myeloid leukemia. 6. Presence of an associated active and/or uncontrolled malignancy: patients with another neoplastic disease, for whom the Investigator has a clinical suspicion of active disease at the time of enrollment. Note: Patients with adequately treated early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia are eligible for this study. Hormonal or adjuvant therapies will be allowed for breast cancer or prostate cancer as long as they are on a stable dose for at least 2 weeks before the first dose. 7. Known active and not controlled hepatitis B or hepatitis C infection. In the event of a positive viral load, please consult with the Sponsor 8. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study) 9. Presence of any severe psychiatric disease or physical condition that, according to the physician´s criteria, contraindicates the inclusion of the patient into the clinical trial 10. Serum creatinine = 250 µmol/l (= 2.5 mg/dL) (unless it is attributable to AML activity) 11. Bilirubin, alkaline phosphatase, or SGOT > 3 times the normal upper limit (unless it is attributable to AML activity) 12. Uncontrolled or significant cardiovascular disease, including any of the following: a. Symptomatic bradycardia of fewer than 50 beats per minute, unless the subject has a pacemaker; b. QTcF >450 msec at Screening. Note: QTcF will be derived from the mean of triplicate readings; c. Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome); d. Systolic blood pressure =180 mmHg or diastolic blood pressure = 110 mmHg; e. History of clinically relevant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes) f. History of a second (Mobitz II) or third-degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker) g. An ejection fraction 10 mg or equivalent corticosteroid daily.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the EFS rate (failure to achieve CR/CRi after 1 or 2 induction cycles, death in CR/CRi or relapse, whichever occurs the first) between the experimental quizartinib containing schedule and standard arms;Primary end point(s): Event-free survival (EFS): failure to achieve CR/CRi after 1 or 2 induction cycles, death in CR/CRi or relapse, whichever occurs the first);Timepoint(s) of evaluation of this end point: Throughout the study; Secondary Objective: To determine the maximum dose tolerated and the recommended phase 2 dose To compare the rate of CR/CRi with MRD negativity after one cycle on induction between arms To compare the DFS, OS, CIR, non-relapse mortality between arms To assess the rate of MRD negativity after consolidation 2, off-therapy, pre-allo-SCT To assess the rate of molecular relapse To assess the feasibility of a maintenance schedule in the SCT and non-SCT setting Subanalyses on efficacy and safety in different populations To assess the impact of potential baseline factors for a response To evaluate early mortality To evaluate the impact on the use of medical resources To evaluate the post-remission schedules according to a predefined risk-adapted strategy Biological procedures to gain insight on the mechanism of action of quizartinib in FLT3-ITD-WT AML To evaluate the clinical benefits, safety, tolerability, and health-related quality of life (HRQOL) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Maximum dose tolerated and recommended phase 2 dose - Rate of CR/CRi with MRD negativity - Adverse events - Disease Free Survival - Rate of MRD negativity - Rate of molecular relapse - Impact of potential baseline factors for a response - Early mortality - Use of medical resources during the treatment phase (antibiotics, transfusions, duration of hospitalization, need of central venous line) - Health-related quality of life ; Timepoint(s) of evaluation of this end point: - Maximum dose tolerated and recommended phase 2 dose: maximum of 59 days since day 1 of induction chemotherapy - Rate of CR/CRi with MRD negativity: throughout the study - Adverse events: throughout the study - Disease Free Survival: throughout the study - Rate of MRD negativity: throughout the study - Rate of molecular relapse: throughout the study - Impact of potential baseline factors for a response: throughout the study - Early mortality: first 60 days - Use of medical resources during the treatment phase (antibiotics, transfusions, duration of hospitalization, need of central venous line): throughout the study - Health-related quality of life: throughout the study | — |
Countries
Spain
Contacts
Public ContactDepartamento de Operaciones
Dynamic Science S.L.
Outcome results
None listed