A Phase II Study of CP-4055 plus Idarubicin as Second Course Remission-Induction Therapy in Patients with Acute Myeloid Leukaemia

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2008-008518-38-FR
• Date of registration: 10/07/2009
• Prospective Registration: Yes
• Primary sponsor: Clavis Pharma ASA
• Public title: A Phase II Study of CP-4055 plus Idarubicin as Second Course Remission-Induction Therapy in Patients with Acute Myeloid Leukaemia
• Scientific title: A Phase II Study of CP-4055 plus Idarubicin as Second Course Remission-Induction Therapy in Patients with Acute Myeloid Leukaemia
• Date of first enrolment: 28/01/2010
• Target sample size: 40
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-008518-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

France, Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with a confirmed diagnosis of AML according to WHO classification (excluding acute promyelocytic leukaemia)
2. Patients who have received one previous standard dose ara-C-containing regimen aiming at induction of complete remission (CR) and who have more than 5 % remaining blast cells in bone marrow on day (d) 14 ± 2, or by other means documented residual disease (i.e. circulating blasts, persistent chloromas, other evident disease).
3. Patients from whom samples for determination of hENT1 status on leukemic blast cells can be taken and prepared at diagnosis and/or at baseline
4. Patients must be 18 years of age or older
5. Patients must have ECOG performance status (PS) of 0 – 2
6. Left ventricular ejection fraction (LVEF) must be = 45 % as measured by MUGA scan or 2D ECHO within 14 days prior to start of therapy.
7. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study
8. Male and female patients must use acceptable contraceptive methods for the duration of time on study, and males also for 3 months after the last elacytarabine dose
9. Patients must be capable of understanding and complying with parameters as outlined in the protocol, and able and willing to sign a written informed consent form
10. Patients must have the following clinical laboratory values:
• Serum creatinine = 1.5 x the institutional upper limit of normal (ULN)
• Total bilirubin = 1.5 x the ULN according to national prescribing information unless considered due to Gilbert’s syndrome
• Alanine aminotransferase (ALT) (SGPT), or aspartate aminotransferase (AST) (SGOT) = 2.5 x the ULN unless considered due to organ leukemic involvement
11. Patients must be eligible for administration of idarubicin according to current national prescribing information for idarubicin

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. A history of allergic reactions to egg, idarubicin and/or other anthracyclines or other components of the products
A history of allergic reactions to ara-C of CTCAE grade 3 or 4
2. Persistent clinically significant and relevant toxicities from the previous course of chemotherapy
3. A cancer history, that according to the investigator might confound the assessment of the study endpoints
4. Patients with prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 300 mg/m2 according to the following calculation index: X/300 + Y/160 < 1 where X is the doxorubicin or equivalent dose in mg/m2 and Y is the mitoxantron dose in mg/m2. These calculations are to be used as guidance as there is no maximum cumulative dose defined in the summary of product characteristics (SPC) for idarubicin. The patient should tolerate minimum one course of combination therapy
5. Active heart disease including myocardial infarction within the previous 3 months, symptomatic coronary disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure. Any NYHA grade 3 or 4
6. Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C
7. Pregnant and nursing patients are excluded because the effects of elacytarabine on a foetus or a nursing child are unknown
8. Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, or psychiatric illness/social situations that may reduce compliance with study requirements
9. Patients receiving hydroxyurea within the last 12 hours prior to treatment on this protocol or any other investigational or standard cytotoxic treatment within the last 14 days, except the first remission-induction course
10. Any medical condition, which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acute Myeloid Leukaemia (AML)

Intervention(s)

Product Name: Elacytarabine (CP-4055) for infusion
Product Code: CP-4055
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: proposed INN: elacytarabine
CAS Number: 188181-42-2
Current Sponsor code: CP-4055
Other descriptive name: 5'-O-(trans-9''-octadecenoyl)1-beta-D arabinofuranosyl cytosine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: ZAVEDOS
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: idarubicinhydroklorid
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-10

Primary Outcome(s)

Primary end point(s): • Incidence of CR + CRp
• hENT1 status in blast cells
• Relation between hENT1 expression level and CR + CRp
• Relapse or death
• Clinical and laboratory adverse events (AEs)

Main Objective: 1. Estimate rate of complete remission (CR), including complete remission except for platelet count < 100 x 109/L (CRp) (CR + CRp rate) in patients with AML who have not attained blast clearance after the first course of a ara-C based remission-induction therapy.

Secondary Objective: 2. Obtain indication on the independence between hENT1 expression level and CR or CRp
3. Obtain guidance on disease free survival (DFS), defined as time from CR + CRp to relapse
4. Obtain guidance on event free survival (EFS), defined as time from day one of therapy until relapse or death from any cause
5. Characterize the safety profile of elacytarabine plus idarubicin in this patient population

Secondary ID(s)

2008-008518-38-DE

CP4055-205