Fludarabine-refractory Chronic Lymphocytic Leukemia (CLL) MedDRA version: 9.1 Level: LLT Classification code 10003948 Term: B-Lymphocytic, CLL (Kiel Classification) refractory
Conditions
Sponsors
Academic Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - CLL confirmed according to the IWCLL Working Group criteria - Binet28 stages A or B with indication for treatment according to IWCLL guidelines (appendix A and B) , Binet C AND - Fludarabine refractory, defined as relapse (any sign of disease recurrence or progression with or without indication for treatment = 6 months following fludarabine containing chemo(immuno)therapy; - Age 18-80 years inclusive; - WHO performance status = 2; - No possibility for rapid reduced intensity allogeneic hematopoietic stem cell transplantation; - At least 4 weeks without any treatment before study entry; - Negative pregnancy test; - 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) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Richter’s transformation; - Suspected or documented CNS involvement by CLL; - Grade 3 cytopenia not due to bone marrow infiltration; - Concurrent medical condition which may increase the risk of toxicity; ? Pleural or pericardial effusion of any grade; - Severe cardiac Symptoms; - Severe pulmonary dysfunction; - Active hepatitis B infection; - History of significant bleeding disorder unrelated to the CLL; - Known HIV positivity; - Clinically significant auto-immune hemolytic anemia (AIHA); - Severe neurological or psychiatric disease; - Significant hepatic dysfunction (serum bilirubin or transaminases = 3 times normal level) except when caused by leukemic infiltration - Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration) - History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma - Concurrent use of CYP3A4 inducers or inhibitors, or QTc-prolonging agents - Active, uncontrolled infections; - Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule; - Female patients of reproductive potential who are not using effective contraception;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the response rate and response quality of dasatinib monotherapy or dasatinib/fludarabine combination in fludarabine refractory CLL patients.;Secondary Objective: - To asses the overall safety profile of this treatment approach - To asses event free survival (i.e. time from registration to induction failure, progression, relapse or death whichever occurs first), progression free survival (i.e. time from registration to disease progression, relapse or death due to CLL whichever occurs first) and disease free survival (i.e. time from CR to relapse) - To asses influence of dasatinib on the expression profile of apoptosis regulatoring genes. - To determine by in vitro analysis whether dasatinib acts synergistically with other immuno-chemotherapeutic agents by co-culture experiments. ;Primary end point(s): Clinical response rate and quality ( CR, PR) at 28 weeks according to the IWCLL Working Group criteria In case of complete responses: minimal residual disease status as assessed by flow cytometry | — |
Countries
Netherlands
Outcome results
None listed