Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome MedDRA version: 14.1 Level: SOC Classification code 10005329 Term: Blood and lymphatic system disorders System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: AC220
Pharmaceutical Form: Oral solution
Trade Name: Mozobil
Product Name: Mozobil
Pharmaceutical Form: Solution for inje
Sponsors
Cardiff University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) They have one of the forms of AML, except Acute Promyelocytic Leukaemia as defined by the WHO Classifcation - this can be any type of de novo or secondary AML - or high risk MDS, defined as greater than 10% marrow blasts. 2) Serum creatinine = 1.5xULN. 3) White cell count of =65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: 1)They have previously received cytotoxic chemotherapy for AML (hydroxycarbimide, or similar low-dose therapy, to control the white count prior to initiation of intensive therapy is not an exclusion) 2) They are in blast transformation of chronic myeloid leukaemia (CML) 3) They have a concurrent active malignancy excluding basal cell carcinoma 4) They are pregnant or lactating 5) They have Acute Promyelocytic Leukaemia 6) Known infection with human immunodeficiency virus (HIV) 7) Patients are not eligible for the AC220 option if they have: -Uncontrolled or significant cardiovascular disease including: -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 or Multiple Gated Acquisition Scan performed either within 1 month prior to study screening or during screening results in a left ventricular ejection fraction 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, or torsades de pointes); any history of arrhythmia will be discussed with the Sponsor's Medical Monitor prior to patient's entry into the study. -Prolonged QTcF interval on pre-entry ECG (=450ms) -Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker) -Heart rate <50/min on pre-entry ECG -Uncontrolled hypertension -Obligate need for a cardiac pacemaker -Complete left bundle branch block -Atrial fibrillation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The AML 18 Pilot Trial is a precursor to a randomised trial (AML 18) and is available to patients with Acute Myeloid Leukaemia (AML, either de Novo, or secondary to either previous cancer treatment or a previous haematological disorder), or high risk myelodysplastic syndrome (MDS). It will look at the feasibility of giving one of three novel treatments in conjunction with standard chemotherapy. The first treatment is a FLT-3 inhibitor called AC220. The second treatment is a CXCR4 inhibitor called Plerixafor. The third intervention will be to add four weekly 1 hour infusions of an established dose of a novel HSP90 inhibitor, Ganetespib to standard chemotherapy. The trial is designed to identify the maximum, tolerated dose, by considering the toxicity associated with each treatment - higher doses/longer treatment courses will be tried only once lower/shorter doses are deemed to be safe. ;Secondary Objective: In addition to looking at toxicity, the trial will consider the outcome of patients - whether they enter remission, and their overall survival - and correlate outcomes with patient characteristics, including some molecular markers. This is important as it may be relevant to future treatment strategies for patients with AML or MDS.; Primary end point(s): The trial endpoints: - Response (CR, CRi, PR) achievement and reasons for failure - 30 day and 8 week mortality - Toxicity, both haematological and non-haematological - Supportive care requirements - Survival at 6 and 12 months | — |
Countries
United Kingdom
Outcome results
None listed