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

NCT ID: NCT01258816

Last Updated: 2013-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-06-30

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.

Conditions

Relapsed/Refractory AML

Keywords

Acute Myeloid Leukaemia (AML); Pharmacokinetics; Elacytarabine; CP-4055

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Elacytarabine for infusion

Elacytarabine 2000 mg/m2/d will be administered as a continuous intravenous infusion (CIV) in a d 1-5 q3w schedule.

Intervention Type: DRUG

Other Intervention Names

CP-4055

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theradex

INDUSTRY

Sponsor Role: collaborator

Syneos Health

OTHER

Sponsor Role: collaborator

CardiaBase

OTHER

Sponsor Role: collaborator

Learn & Confirm

UNKNOWN

Sponsor Role: collaborator

Clavis Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Knapper, MD

Role: PRINCIPAL_INVESTIGATOR

Cardiff University

Locations

ICO - Hospital Duran i Reynals

Barcelona, Catalonia, Spain

Hospital General de la Vall d' Hebron

Barcelona, , Spain

Hospital San Pedro Alcantara

Cáceres, , Spain

Brighton & Sussex University Hospitals NHS Trust

Brighton, , United Kingdom

University Hospital of Wales, Cardiff

Cardiff, , United Kingdom

St Bartholomew's Hospital

London, , United Kingdom

Countries

Spain; United Kingdom

References

Knapper S, Chevassut T, Duarte R, Bergua JM, Salamero O, Johansen M, Jacobsen TF, Hals PA, Rasch W, Gianella-Borradori A, Smith M. Elacytarabine in relapsed/refractory acute myeloid leukaemia: an evaluation of clinical efficacy, pharmacokinetics, cardiac safety and effects on lipid profile. Leuk Res. 2014 Mar;38(3):346-51. doi: 10.1016/j.leukres.2013.12.011. Epub 2013 Dec 25.

Reference Type: DERIVED

PMID: 24433865 (View on PubMed)

Other Identifiers

CP4055-109

Identifier Type: -

Identifier Source: org_study_id