AML LI1

Conditions: Acute myeloid leukemia and high-risk myelodysplastic syndrome
MedDRA version: 17.1Level: SOCClassification code 10005329Term: Blood and lymphatic system disordersSystem Organ Class: 10005329 - Blood and lymphatic system disorders

Registration Number: EUCTR2011-000749-19-DK

Lead Sponsor: Cardiff University

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 1000

Inclusion Criteria

Patients are eligible for the LI-1 trial if:
•They have one of the forms of acute myeloid leukaemia, except Acute Promyelocytic Leukaemia as defined by the WHO Classification (Appendix A) this can be any type of de novo or secondary AML – or high risk Myelodysplastic Syndrome, defined as greater than 10% marrow blasts (RAEB-2).
Note: patients with prior MDS who have received azacitidine may enter the trial only if they have progressed to AML
•They should be over the age of 60
•They have given written informed consent.
•Male patients with partners of childbearing potential must agree to use effective contraception during the study period and a period of 3 months after the last dose of study drug.
Please note for the AC220 (quizartinib) and ganetespib interventions:
•Additional cardiac criteria must be met
•Electrolyte levels of Potassium, Magnesium and Calcium must be within the institutional normal range
Male patients must also use effective contraception
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 900

Exclusion Criteria

Patients are not eligible for the LI-1 trial if:
•They are less than 60 years of age
•They have previously received cytotoxic chemotherapy for AML. [Hydroxycarbamide, or similar low-dose therapy, to control the white count is not an exclusion criterion].
•They are in blast transformation of chronic myeloid leukaemia (CML).
•They have a concurrent active malignancy under treatment.
•They are pregnant or lactating.
•They have Acute Promyelocytic Leukaemia.
•Known infection with human immunodeficiency virus (HIV)
•Total bilirubin = 1.5 x ULN, unless due to Gilbert’s syndrome
•Aspartate aminotransferase (AST) = 2.5 x ULN and/or alkaline phosphatase =2.5 x ULN
•Serum creatinine = 175µmol/L
•History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 6 months

For AC220 (quizartinib) and ganetespib treatment the following criteria make a patient ineligible for that randomisation:
•A myocardial infarction within 12 months
•Uncontrolled angina within 6 months
•Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless an echocardiogram (ECHO) or Multiple Gated Acquisition Scan (MUGA) performed either within 1 month prior to study screening or during screening results in a left ventricular ejection fraction (LVEF) that is = 45% (or institutional lower limit of normal value).
•Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes [TdP]) or any history of arrhythmia will be discussed with the Clinical Coordinator/Safety Physician prior to patient’s entry into the study.
•Prolonged QTcF interval on pre-entry ECG (=450 ms)
•Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker
•Heart rate < 50/minute on pre-entry ECG
•Uncontrolled hypertension
•Obligate need for a cardiac pacemaker
•Complete left bundle branch block
•Uncontrolled atrial fibrillation