Activity & Safety Study of Lenalidomide & Rituximab as Non-chemotherapy Based Therapy on Chronic Lymphocytic Leukemia
- Registration Number
- NCT01185262
- Lead Sponsor
- MD Anderson International Spain SA
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
- Recurrent and refractory CLL patients that have received at least one previous treatment with purine analogs.
- Adequate liver function and renal function.
- ECOG performance status ≤ 2.
- Signed informed consent
- Male and female patients who are fertile agree to use an effective barrier method of birth control to avoid pregnancy.
- Positive serological markers for hepatitis B with the exception of HBsAc in previously vaccinated patients
- Pregnant patients
- HIV infection
- Concurrent chemotherapy or immunotherapy
- Other malignancy within the last 2 years, except for localized cutaneous carcinoma
- Neurological impairment precluding understanding of protocol and the entailed visits and procedures.
- Patients with Renal insufficiency that requires dialysis.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lenalidomida, Rituximab Lenalidomida and 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).
- Primary Outcome Measures
Name Time Method Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients. 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).
- Secondary Outcome Measures
Name Time Method To determine the time to treatment failure. 5 months Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
To determine the toxicity profile of LenRtx. 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). 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
To determine the molecular response rate. 5 months Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
Trial Locations
- Locations (7)
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Clínico de Salamanca
🇪🇸Salamanca, Spain
MD Anderson Internacional España
🇪🇸Madrid, Spain
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain