relapsed/refractory acute myeloid leukemia MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Quizartinib
Product Code: AC220
Pharmaceutical Form: Coated tablet
INN or Proposed INN: QUIZARTINIB
CAS Number: 950769-58-
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 prior to the first screening procedure. Informed consent form must be signed by the patient and the Investigator. 2. Patients aged 18 to 70 years old at the time of screening. 3. First R/R AML defined as: • First relapse after frontline intensive chemotherapy (with or without prior alloSCT), irrespectively of the duration of the first CR. Patients previously treated with a FLT3 inhibitor different from quizartinib, can be included. • First refractory disease (defined as patients not achieving at least a PR after first induction cycle and/or not achieving CR/CRi after first 2 cycles). Patients previously treated with a FLT3 inhibitor different from quizartinib, can be included. 4. Non-APL AML. 5. Considered for intensive approach as per Investigator judgment. 6. ECOG 0-2. 7. No contraindications for quizartinib. 8. No contraindications for intensive chemotherapy. 9. No severe organ function abnormalities. 10. No active relevant GVHD. 11. For the Phase II, FLT3-ITD patients will represent 50% of the study cohort (FLT3-TKD are not excluded but included in the FLT3-ITD-WT group). 12. Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception upon enrollment, during the treatment period and for 6 months following the last dose of investigational drug or cytarabine, whichever is later. 13. Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential) upon enrollment, during the treatment period, and for 6 months following the last dose of investigational drug or cytarabine, whichever is later. 14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 82 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Patients with genetic diagnosis of acute promyelocytic leukemia. 2. Blastic phase of bcr/abl chronic myeloid leukemia. 3. Patients with other neoplastic disease, for whom the Investigator has 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 if they are on a stable dose for at least 2 weeks prior to first dose. 4. Presence of any severe psychiatric disease or physical condition/comorbidity that, according to the physician´s criteria, contraindicates the inclusion of the patient in the clinical trial 5. Serum creatinine > or = 250 µmol/l (> or = 2.5 mg/dL) (unless it is attributable to AML activity). 6. Bilirubin, alkaline phosphatase, or SGOT >3 times the upper normal limit (unless it is attributable to AML activity). 7. Uncontrolled or significant cardiovascular disease, including any of the following: - Symptomatic bradycardia of less than 50 beats per minute, unless the subject has a pacemaker. - QTcF >450 ms at screening. Note: QTcF will be derived from the mean of triplicate readings. - Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome) - History of clinically relevant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes). - History of 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). - History of uncontrolled angina pectoris or myocardial infarction within 6months prior to Screening. - History of New York Heart Association Class 3 or 4 heart failure. - Complete left bundle branch block. - Right bundle branch and left anterior hemiblock (bifascicular block) - Infarction (MI) within 3 months. - Systolic blood pressure > or = 180 mmHg or diastolic blood pressure > o =110 mmHg - A previously known left ventricle ejection fraction 10 mg or equivalent corticosteroid daily 12. Any patients with known significant impairment in gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of quizartinib 13. History of hypersensitivity to any excipients in the quizartinib tablets. 14. Females who are pregnant or breastfeeding. 15. Iso
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To find the recommended Phase II dose (RP2D) Phase II: To assess the rate of CR/CRi after one cycle of FLAG-QUIDA ; Secondary Objective: • To assess the rate of CR/CRi with MRD negativity after one cycle of induction. • To compare the rate of CR/CRi achieved in the Phase II cohort with a matched historical control (among more than 460 patients treated with FLAG-IDA in the PETHEMA Foundation registry). • To assess OS at 1 and 2 years. • To assess safety and tolerability of the schedule. • To assess DFS (time to events, death in CR or relapse, whichever occurs the first), EFS (resistance, death in CR or relapse, whichever occurs the first), CIR, non-relapse mortality • To assess long term follow-up (i.e., 3 years). • To assess the rate of MRD negativity pre-HSCT. • To assess the feasibility of a maintenance schedule in the HSCT and non-HSCT setting. • Sub-analyses in different populations (FLT3-ITD, secondary AML, NPM1, IDH positive, and according to the type of relapse) • Other secondary objectives ; Primary end point(s): Phase I: to find the maximum tolerated dose of the combination of quizartinib and FLAG-IDA regimen (FLAG-QUIDA) Phase II: to assess the rate of CR/CRi after one cycle of FLAG-QUIDA ; Timepoint(s) of evaluation of this end point: Phase I: by completion of each cohort Phase II: after one cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Disease-free survival (DFS), defined as time from the first documentation of remission to the documentation of disease recurrence or death - Overall survival (OS), defined as the number of days from randomization until death from any cause ;Timepoint(s) of evaluation of this end point: At each study visit | — |
Countries
Spain
Contacts
Public ContactGestión de proyectos
Fundación Pethema
Outcome results
None listed