Activity & Safety Study of Lenalidomide & Rituximab as Non-chemotherapy Based Therapy on Chronic Lymphocytic Leukemia (LLC-LENAR-08)
|ClinicalTrials.gov Identifier: NCT01185262|
Recruitment Status : Completed
First Posted : August 19, 2010
Last Update Posted : September 30, 2013
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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Drug: Lenalidomida and Rituximab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of the Activity and Safety of Lenalidomide and Rituximab as Non-chemotherapy Therapy for Patients With Recurrent and Refractory Chronic Lymphocytic Leukemia|
|Study Start Date :||April 2009|
|Actual Primary Completion Date :||December 2012|
|Actual Study Completion Date :||September 2013|
Experimental: Lenalidomida, Rituximab
Phase I: Lenalidomide will be administered from day 1 to 21 of 28 days cycles, escalating doses (from 2,5mg to 25 mg).Rituximab dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles).
Drug: Lenalidomida and Rituximab
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.
- Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients. [ Time Frame: 5 months ]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).
- To determine the toxicity profile of LenRtx. [ Time Frame: 5 months ]Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
- To determine the time to treatment failure. [ Time Frame: 5 months ]Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
- To determine the molecular response rate. [ Time Frame: 5 months ]Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
- To determine the clinical response rate (combined morphological and flow cytometry criteria). [ Time Frame: 5 months ]6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01185262
|Hospital Universitario Reina Sofía|
|Córdoba, Spain, 14004|
|MD Anderson Internacional España|
|Madrid, Spain, 28033|
|Hospital Universitario La Paz|
|Madrid, Spain, 28046|
|Hospital Clínico de Salamanca|
|Salamanca, Spain, 37007|
|Hospital Virgen del Rocío|
|Sevilla, Spain, 41013|
|Hospital Clínico Universitario de Valencia|
|Valencia, Spain, 46010|
|Hospital Universitario Miguel Servet|
|Zaragoza, Spain, 50009|
|Principal Investigator:||José F Tomas, MD||MD Anderson Internacional España|