The rationale for combining lenalidomide with rituximab derives from preclinical observations suggesting that lenalidomide may enhance the ADCC (antigen-dependent cellular cytotoxicity) triggered by monoclonal antibodies such as rituximab. Lenalidomide augments NK cytotoxicity by increasing CD56dimCD3 subset, in addition to inducing IL-2 in T cells. These results provide the cellular and molecular basis for the use of lenalidomide as an adjuvant in immunotherapeutic strategies of monoclonal antibodies (mAb)-based therapies. The combination lenalidomide-rituximab was tested in lymphoma cell lines but not specifically on CLL cell lines. However the observed synergism was attributed to NK cells expansion, thus lending support to the notion that this synergism may operate in other B-cell lymphoproliferative malignancies. The objective was to develop a non-cytotoxic and effective treatment for CLL that would fulfill an unmet medical need, as a significant proportion of CLL patients are elderly and frail. These patients experience an excess in chemotherapy induced toxicity, often preventing the completion of the planned treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Lenalidomide: Oral use. It will be administered from day 1 to 21 of 28 days cycles in a total of 6 cycles. Rituximab, intravenous use. The dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles). In the first cycle Rituximab will be administered in two divided doses:100mg/m2 total on day 1 and the rest up to 375mg/m2 on day 2. If lenalidomide treatment starts on day 1, Rituximab will be administered, in this first cycle, on days -2 (100 mg/m2) and -1 (275 mg/m2). In the second and subsequent cycles, 500 mg/m2 of Rituximab will be administered on day -1.
Hospital Universitario Reina Sofía
Córdoba, Córdoba, Spain
MD Anderson Internacional España
Madrid, Madrid, Spain
Hospital Universitario La Paz
Madrid, Madrid, Spain
Hospital Clínico de Salamanca
Salamanca, Salamanca, Spain
Hospital Virgen del Rocío
Seville, Sevilla, Spain
Hospital Clínico Universitario de Valencia
Valencia, Valencia, Spain
Hospital Universitario Miguel Servet
Zaragoza, Zaragoza, Spain
Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression. Module I: patients on every cohort will have the same dose during treatment, except if they experiment DLT, in which case dose will be decreased (unless they are on the first dose level).
Time frame: 5 months
To determine the toxicity profile of LenRtx.
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
Time frame: 5 months
To determine the time to treatment failure.
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
Time frame: 5 months
To determine the molecular response rate.
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
Time frame: 5 months
To determine the clinical response rate (combined morphological and flow cytometry criteria).
6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression
Time frame: 5 months
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