A programme of development for older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome

Phase 2

• Conditions: Acute myeloid leukaemia (AML); myelodysplastic syndrome; Cancer - Leukaemia - Acute leukaemia; Blood - Haematological diseases

• Registration Number: ACTRN12612000848808
• Lead Sponsor: Australasian Leukaemia and Lymphoma Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-08-13
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1.Acute myeloid leukaemia (except Acute Promyelocytic Leukaemia) as defined by the WHO Classification. This can be any type of de novo or secondary AML – or high risk Myelodysplastic Syndrome (greater than 10% blasts, RAEB-2). MDS patients who have received azacitidine are not eligible for this trial, but patients with less than 10% who have failed a demethyation agent and developed AML may enter the trial.
2.Over the age of 60
3.Given written informed consent.

For the AC220 (quizartinib), tosedostat and ganetespib interventions:
4.Cardiac criteria must be met
5.Electrolyte levels of Potassium, Magnesium and Calcium (adjusted) must be within the institutional normal range

Male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential.

Exclusion Criteria

1.Less than 60 years of age
2.Previously received cytotoxic chemotherapy for AML (hydroxycarbamide, or similar low-dose therapy, to control the white count is not an exclusion criterion. Previous treatment with a demethylating agent for MDS less than 10% blasts is not an exclusion).
3.Blast transformation of chronic myeloid leukaemia (CML)
4.Concurrent active malignancy under treatment
5.Pregnant or lactating
6.Acute Promyelocytic Leukaemia
7.Known infection with human immunodeficiency virus (HIV)
8.Total bilirubin greater than or equal to 1.5 x ULN, unless due to Gilbert’s syndrome
9.Aspartate aminotransferase (AST) greater than or equal to 2.5 x UL and/or alkaline phosphatase greater than or equal to 2.5 x ULN
10.Serum creatinine greater than or equal to 175µmol/L
11.History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 6 months

For AC220 (Quizartinib), Tosedostat and Ganetespib treatment the following criteria make a patient ineligible for that randomisation:
12.A myocardial infarction within 12 months
13.Uncontrolled angina within 6 months
14.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 greater than or equal to 45% (or institutional lower limit of normal value).
15.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.
16.Prolonged QTcF interval on pre-entry ECG (greater than or equal to 450 ms)
17.Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker)
18.Heart rate less than 50/minute on pre-entry ECG
19.Uncontrolled hypertension
20.Obligate need for a cardiac pacemaker
21.Complete left bundle branch block
22.Uncontrolled atrial fibrillation

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Complete remission (CR) defined as:<br>* Cellularity of marrow should be at least 20% with evidence of tri-lineage regeneration.<br>* Less than 5% blasts. <br>* No Auer rods. <br>* No extra-medullary disease. <br>* Peripheral blood count recovery to 100 x10^9/l <br>* Neutrophil recovery to 1.0 x 10^9/l <br><br>[10-14 days after completion of cycle 1]

Secondary Outcome Measures

Name	Time	Method
overall survival[After 25% and 50% of the required number of events have been seen]