Acute Myeloid Leukaemia (AML)
Conditions
Interventions
Product Name: Elacytarabine (CP-4055) for infusion
Product Code: CP-4055
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: INN: elacytarabine
CAS Number: 188181-42-2
Current Sponsor co
Sponsors
Clavis Pharma ASA
Eligibility
Sex/Gender
All
Inclusion 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 cytarabine containing regimen aiming at induction of complete remission (CR), and who have more than 5 % remaining blast cells in bone marrow following the first course of remission-induction or by other means documented residual disease (i.e. circulating blasts, persistent chloromas, other evident disease from day 12 on). 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: a) Serum creatinine = 1.5 x the institutional upper limit of normal (ULN) b) Total bilirubin = 1.5 x the ULN unless considered due to Gilbert’s syndrome c) 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
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 cytarabine of CTCAE grade 3 or 4 2. Persistent clinically significant and relevant non-haematological 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) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Determine the rate of complete remission (CR), including complete remission with incomplete blood count recovery (CRi) (CR + CRi rate) in patients with AML who have not attained blast clearance after the first course of a cytarabine based remission-induction therapy;Secondary Objective: 2. Obtain an indication of the independence between human equilibrative nucleoside transporter 1 (hENT1) expression level and CR or CRi 3. Duration of disease free survival (DFS), defined as time from CR + CRi to relapse 4. Duration of 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 ;Primary end point(s): 1. Incidence of CR + CRi 2. hENT1 expression in blast cells 3. Relation between hENT1 expression level and CR + CRi 4. Relapse or death 5. Clinical and laboratory adverse events (AEs) | — |
Countries
France, Germany
Outcome results
None listed