Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML)

Korábbi kezelés

• Prior treatment for AML, except for the following allowances:
  • Leukapheresis d) Treatment for hyperleukocytosis with hydroxyurea
• 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.

Más betegség

• Known active and not controlled hepatitis B or hepatitis C infection. In the event of a positive viral load, please consult with the Sponsor
• Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)
• 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
• History of hypersensitivity to any excipients in the quizartinib/placebo tablets
• Any patients with known significant impairment in gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of quizartinib.
• Active acute or chronic Graft-Versus-Host-Disease (GVHD) requiring prednisone >10 mg or equivalent corticosteroid daily.

Laborértékek

• Serum creatinine ≥ 250 μmol/l (≥ 2.5 mg/dL) (unless it is attributable to AML activity)
• Bilirubin, alkaline phosphatase, or Serum glutamic oxaloacetic transaminase (SGOT) > 3 times the normal upper limit (unless it is attributable to AML activity)
• Uncontrolled or significant cardiovascular disease, including any of the following:
  • Symptomatic bradycardia of fewer than 50 beats per minute, unless the subject has a pacemaker;
  • QT Comparison of Fridericia's (QTcF) >450 msec 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);
  • Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥ 110 mmHg;
  • History of clinically relevant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes)
  • 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)
  • An ejection fraction <45%
  • History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening
  • History of New York Heart Association Class 3 or 4 heart failure
  • Right bundle branch and left anterior hemiblock (bifascicular block), complete left bundle branch block

Életkor

• Age <18 years or >70 years

Egyéb

• Patients with a genetic diagnosis of acute promyelocytic leukemia
• ECOG performance status of 3 or 4
• Blastic phase of bcr/abl chronic myeloid leukemia.
• Females who are pregnant or breastfeeding

• 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.
• Diagnosis of untreated AML (according to the World Health Organization (WHO) 2008/2016 definition)
• Age ≥ 18 and ≤70 years old at the time of screening
• Non-FLT3-ITD (allelic ratio <0.03) at diagnosis
• Considered eligible to receive intensive chemotherapy as per investigator judgment
• Eastern Cooperative Oncology Group (ECOG) 0-2
• No contraindications for quizartinib
• The subject is receiving standard "7+3" induction chemotherapy regimen as specified in the protocol
• No severe organ function abnormalities
• Not included in other first-line trials
• Cardiac ejection fraction ≥ 45% assessed by echocardiography or multiple-gated acquisition (MUGA).
• 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 3 months following the last dose of investigational drug or cytarabine, whichever is later
• 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 3 months following the last dose of investigational drug or cytarabine, whichever is later
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.