None listed
Conditions
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ¨ Age 18-65 years, inclusive ¨ Subjects with - a cytopathologically confirmed diagnosis of AML according WHO classification (excluding acute promyelocytic leukaemia) or - a diagnosis of refractory anemia with excess of blasts (RAEB) and IPSS score =1.5 or - patients with therapy-related AML/RAEB or - patients with biphenotypic leukemia (Appendices A1 and A2). ¨ Adequate renal and hepatic function tests as indicated by the following laboratory values: - Serum creatinine =1.0 mg/dl (= 88.7 micromol/L); if serum creatinine >1.0 mg/dl (>88.7 micromol/L), then the glomerular filtration rate (GFR) must be >60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where the predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine in mg/dl)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black) NOTE: if serum creatinine is measured in micromol/L, recalculate it in mg/dl according to the equation: 1 mg/dl = 88.7 micromol/L) and used above mentioned formula. - Serum bilirubin =1.5 × upper limit of normal (ULN) - Aspartate transaminase (AST)/alanine transaminase (ALT) =2.5 × ULN - Alkaline phosphatase = 2.5 × ULN ¨ WHO performance status 0, 1 or 2 (see Appendix I) ¨ Written informed consent 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: ¨ Acute promyelocytic leukaemia ¨ Previous treatment for AML or RAEB, except hydroxyurea ¨ Concurrent history active malignancy in two past years prior to diagnosis except for: - basal and squamous cell carcinoma of the skin - in situ carcinoma of the cervix ¨ Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etcetera), ¨ Cardiac dysfunction as defined by: - Myocardial infarction within the last 6 months of study entry, or - Reduced left ventricular function with an ejection fraction < 50% as measured by MUGA scan or echocardiogram (another method for measuring cardiac function is acceptable), or - Unstable angina, or - Unstable cardiac arrhythmias ¨ Pregnant or lactating females ¨ Unwilling or not capable to use effective means of birth control
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For part A of the study: ¨To determine the feasibility of Clofarabine when given at three possible dose levels together with standard induction cycles I and II in patients with AML/ RAEB with IPSS>=1.5 in a prospective comparison to standard induction cycles I and II without Clofarabine. For part B of the study: ¨To evaluate the effect of Clofarabine at the selected feasible dose level when combined with remission induction chemotherapy cycles I and II as regards clinical outcome (“event-free survival”) in comparison to remission induction cycles I and II with no addition of Clofarabine in a phase III study. ;Secondary Objective: To investigate the clinical efficacy of Clofarabine when combined with remission induction I & II: in Part A with regard to complete remission (CR) rate at different dose levels of Clofarabine. In Part B with regard to the CR rate, disease free survival (DFS), risk of relapse and overall survival (OS) in all patients, in molecularly and cytogenetically distinguishable subsets with regard to the CR rate, DFS, risk of relapse and OS and the tolerance and toxicity To investigate - the effect of Clofarabine on peripheral CD34 cell numbers for autologous peripheral blood transplantation - the prognostic value of molecular markers and gene expression profiles of the leukemia assessed at diagnosis - the treatment effects according minimal residual disease measurements following therapy by standardized sampling of marrow/blood - the outcome of allogeneic sibling or unrelated donor SCT and autologous SCT in cytogenetically and molecularly defined prognostic subgroups of patients ;Primary end point(s): Part A of study: Occurrence of DLT and duration of myelosuppression of the combination of Clofarabine at three selected dose levels. DLT is defined as ¨Death ¨Any non hematological toxicity CTCAE grade = 4, occurring within 30 days after start of cycles I or II and before the start of the next cycle or a new treatment respectivel | — |
Countries
Belgium, Netherlands, Sweden
Contacts
Public ContactHOVON Data Center
HOVON
Outcome results
None listed