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

Phase 1

Completed

• Conditions: Relapsed/Refractory AML

• Registration Number: NCT01258816
• Lead Sponsor: Clavis Pharma

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2010-11-26
• Study First Submitted QC: 2010-12-10
• Study First Posted: 2010-12-13
• Primary Completion: 2013-05
• Study Completion: 2013-06
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-20
• Last Update Posted: 2013-09-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

Not provided

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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Characterise the pharmacokinetics of elacytarabine in patients with relapsed/refractory Acute Myeloid Leukaemia	During first week of treatment course	Collection of pheripheral blood samples at specified time points during first week of the treatment course for PK analyses

Secondary Outcome Measures

Name	Time	Method
Investigate the activity of elacytarabine measured as remission rate (CR + CRi)	After each course	Bone marrow and/or blood examination
Number of patients with Adverse Events as a measure of safety and tolerability	Continuously during study
Evaluate the cardiac safety of elacytarabine with focus on the QT/QTc intervals	During the first week of treatment	Triplicate 12-lead ECG assessments will be done at specified time points before, during and after infusion

Trial Locations

Locations (6)

Hospital San Pedro Alcantara; 🇪🇸 Cáceres, Spain

ICO - Hospital Duran i Reynals; 🇪🇸 Barcelona, Catalunya, Spain

University Hospital of Wales, Cardiff; 🇬🇧 Cardiff, United Kingdom

Brighton & Sussex University Hospitals NHS Trust; 🇬🇧 Brighton, United Kingdom

Hospital General de la Vall d' Hebron; 🇪🇸 Barcelona, Spain

St Bartholomew's Hospital; 🇬🇧 London, United Kingdom