The Pharmacokinetics and Cardiac Properties of Elacytarabine (CP-4055)

A Phase I Study of the Human Pharmacokinetics and Cardiac Safety of Elacytarabine

The purpose of the study is to investigate the pharmacokinetics (PK) and cardiac properties of elacytarabine in patients with relapsed or refractory Acute Myeloid Leukaemia (AML). The efficacy and tolerability of elacytarabine will also be assessed.

Elacytarabine is an investigational drug which is not commercially available. It consists of a fatty acid that is connected to cytarabine which is commonly used in treatment of AML. Due to the connection to a fatty acid, elacytarabine might have an increased uptake in blast cells and thereby increased efficacy.

The characterisation of the pharmacokinetics of an investigational drug, as well as the cardiac safety are essential. The PK of both elacytarabine and its metabolites will be assessed at defined timepoints before, during and after infusion. The cardiac safety of elacytarabine will be evaluated by triplicate ECG recordings at the same time points as the PK assessments.

Elacytarabine will be given as a continuous infusion for 5 days. The patients may continue with further courses of elacytarabine as long as the patient benefits from treatment with elacytarabine.

Inclusion¨Criteria:

1. Patients must have relapsed / refractory AML according to WHO classification (excluding acute promyelocytic leukaemia)
2. Patients must have ECOG Performance Status (PS) of 0 - 2
3. Patients must be 18 years of age or older
4. Women of child-bearing potential must have a negative serum or urine pregnancy test within two weeks prior to treatment start
5. Male and female fertile patients must use adequate contraception for the duration of the study, and males also for 3 months after the last elacytarabine dose
6. Patients must be capable of understanding and complying with protocol requirements, and they must be able and willing to sign a written informed consent

Exclusion Criteria:

1. A history of allergic reactions to egg. A history of CTCAE grade 3 or 4 allergic reactions to ara-C of
2. A history of cancer that according to the investigator might confound the assessment of the endpoints of the clinical study
3. Known positive status for human immunodeficiency virus (HIV)
4. Pregnant and nursing patients
5. Uncontrolled inter-current illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that will limit compliance with study requirements
6. Impairment of hepatic or renal function to such an extent that the patient, in the opinion of the investigator, will be exposed to an excessive risk if entered into the clinical study
7. Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medications, or uncontrolled congestive heart failure. Any NYHA grade 3 or 4
8. A history of familial long QT syndrome
9. Patients with history of serious ventricular arrhythmia (VT or VT)
10. ECG criteria at the eligibility visit: QTc ≥ 480 msec calculated using Fridericia's correction (QTcF = QT/RRO,33) or bradycardia (<50bpm) or criteria for left ventricular hypertrophy
11. treatment with any medications known to produce QT prolongations
12. Treatment with hydroxyurea or 6-mercaptopurine within the last 12 hours prior to treatment on this protocol or any other investigational or standard cytotoxic treatment within the last 14 days

9. Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities