Despite certain notable progress, treatment of patients with Chronic Lymphatic Leukemia (CLL) is still disappointing. Although thanks to the use of treatment of (immune) chemotherapy, mainly based on fludarabine, rituximab and alemtuzumab, the rate of complete response (CR) has increased from minus 10% observed when clorambucil was the core of the therapy to a 60-70%, with time all patients relapse and most of them die at the end due to the disease or to involvements related to the treatment. Progress when understanding the CLL biology have cleared a series of aspects: 1) there is a significant proportion of CLL cells actively copying themselves, contrary to the opinion that most of CLL cells are in G0 phase of the cell cycle; 2) Immune regulatory mechanism basically measured by T cells and NK cells have an important role in the continuous accumulation of CLL cells in the body; 3) Cells of the stroma are essential to maintain survival of CLL cells through a series of cytokines or chemokines. Under the light of this evidence, it is worth studying new treatment modes directed not only to CLL cells but also to the microenvironment and immune functions. Lenalidomide is being investigated as treatment for several oncologic indications including myelodysplastic syndromes, multiple myeloma and non-Hodgkin lymphoma. Within the scope of CLL, it has been proved that lenalidomide is active in patients with relapsing / treatment resistant CLL patients. Forty five patients with relapsing CLL, 51% resistant to fludarabine, where included in a phase II study and were treated orally with 25 mg of lenalidomide on days 1 to 21 of a cycle of 28 days. The total response rate was of 47% with up to a 9% of complete responses. The combination of lenalidomide with dexamethasone is being investigated in multiple myeloma and has revealed as a highly efficient treatment in relapsing/ treatment resistant patients as well as in those newly diagnosed. Bearing in mind that both drugs, lenalidomide and dexamethasone, are clinically active in CLL the investigators have designed a study with this combination in relapsing or treatment resistant patients following treatments containing fludarabine which do not meet the requirements for an intensive rescue treatment. Given initial doses of 10 and 25 mg of lenalidomide daily may be associated with tumor lysis cases, it is proposed a low initial dose of lenalidomide in the first cycle 2.5mg., with further increases to prevent the occurrence of tumor lysis syndrome
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Lenalidomide - Revlimid®: an analogue of thalidomide, is an immunomodulator agent with anti-angiogenic properties. The chemical name is 3-(4 ́-aminoisoindoline-1 ́ona)-1- piperidine-2,6-dione. REVLIMID® (lenalidomide) is available in capsules of 5 mg, 10 mg and 15 mg p.o.. Each capsule contains lenalidomide as active ingredient and the following non active ingredients: anhydrous lactose, microcrystalline cellulose, sodium croscarmellose and magnesium stearate.
Dexamethasone will be administered as 20 mg/day (on days 1 to 4) for oral administration.
Centro Médico Teknon
Barcelona, Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, Spain
Hospital Universitari Valle Hebron
Barcelona, Barcelona, Spain
Hospital Clinico Universitario de Barcelona
Barcelona, Barcelona, Spain
Hospital Joan XXIII
Tarragona, Tarragona, Spain
Hospital Clínico Universitario de Valencia
Valencia, Valencia, Spain
To assess the safety of the association of lenalidomide and dexamethasone in patients with relapsed or refractory CLL
The first step will be an interim analysis of toxicity to determine the safety of the first lenalidomide cohort dosage (2.5 mg/day). This analysis will be performed after six subjects complete 3 months of treatment. A second analysis of toxicity will be performed after the second lenalidomide dosage cohort (six patients with 5mg/day) complete 3 months of treatment.
Time frame: At the finalization of the second cycle of the treatment of the last patient (average 5 months of last patient inclusion date)
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Duration of response.
Time frame: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Time to response.
Time frame: Average of 9 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Progresion-free survival.
Time frame: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Treatment response.
Time frame: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Overall survival.
Time frame: Average of 20 months from the last patient inclusion.
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