Leukemia, Lymphocytic, Chronic, B-Cell
Conditions
Keywords
CLL, untreated, immune therapy, dose escalation, maximum tolerated dose, maintenance therapy, Lenalidomide, Rituximab, Fludarabine
Brief summary
The aim of this study is to determine the maximal tolerated dose level of lenalidomide combined with fludarabine/rituximab in the therapy of patients with previously untreated CD20-positive chronic lymphocytic leukemia. Following a dose escalation phase lenalidomide will be given at the pre-determined maximum tolerated dose in combination with rituximab to further determine the efficacy and tolerability of this regimen.
Detailed description
This is a non-randomized, multicenter, open-label, single-arm Phase I/II study in patients with previously untreated CD20-positive CLL. Phase I of the study will evaluate the maximal tolerated lenalidomide dose level in combination with fludarabine/rituximab chemoimmunotherapy in 10 patients. Phase II will determine efficacy using the combination in the previously defined maximal tolerated dose. Both phases will be followed by a maintenance phase evaluating the tolerability and possibility to further improve response quality.
Interventions
DRUGLenalidomide
Dose escalation stage: starting dose 2.5mg/d, dose escalation via 5/10/15/20/25 mg/d every 28 days if no dose-limiting toxicity. During maintenance stage dosing on days 1-28 for max. 6 months at maximum tolerated dose reached during dose escalation stage.
DRUGFludarabine
25 mg/m2 i.v. d1-3 or 40 mg/m2 po d1-3 every 28 days for 6 cycles during dose escalation stage.
BIOLOGICALRituximab
Dose escalation stage: 375 mg/m2 i.v. d4 Cycle 1, 500 mg/m2 i.v. d1 Cycles 2-6. Maintenance stage: 375 mg/m2 i.v. at 2/4/6 months after end of escalation stage.
Sponsors
Celgene Corporation
Roche Pharma AG
Arbeitsgemeinschaft medikamentoese Tumortherapie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* B-CLL (CD23+, CD5+, CD19+, CD20+) * Treatment indication according to NCI criteria * Age \>= 18 yrs * No previous treatment of CLL by chemo-, radio- or immunotherapy * Life expectancy \> 6 months * Written informed consent * Women of non-childbearing potential or women of childbearing potential and men using effective contraception
Exclusion criteria
* Active bacterial, viral or fungal infection * Positivity for HIV, Hepatitis B or C * Reduce organ functions and bone marrow dysfunction not due to CLL * Creatinine clearance below 30 ml/min * Patients with medical conditions requiring long-term use of systemic corticosteroids during study treatment * Patients with a history of severe cardiac disease * Other known co-morbidity with the potential to dominate survival * Transformation to aggressive B-cell malignancy * Known hypersensitivity to humanised monoclonal antibodies or any of the study drugs * Pregnant or breast-feeding women * Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Lenalidomide Maximum Tolerated Dose | Dose escalation stage |
Secondary
| Measure | Time frame |
|---|---|
| Safety Profile of Lenalidomide/Rituximab | Study duration |
| Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment | Dose escalation stage |
| Response rate for Lenalidomide/Rituximab combination therapy | Study Duration |
| Safety profile of Lenalidomide/Fludarabine/Rituximab treatment | Study Duration |
| Changes in Quality of Life scores | Study Duration |
| Risk factors and clonal evolution | Study Duration |
| Response rate by 4-colour flow cytometric MRD analysis | Study Duration |
Countries
Austria
Outcome results
None listed