Clinical trial NCT01185262: Activity & Safety Study of Lenalidomide & Rituximab as Non-chemotherapy Based Therapy on Chronic Lymphocytic Leukemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Keywords: Recurrent and refractory chronic lymphocytic leukemia
Lead sponsor: MD Anderson International Spain SA
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2010-08-19
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
timeFrame: 5 months
Secondary outcomes:
measure: To determine the toxicity profile of LenRtx.
timeFrame: 5 months
measure: To determine the time to treatment failure.
timeFrame: 5 months
measure: To determine the molecular response rate.
timeFrame: 5 months
measure: To determine the clinical response rate (combined morphological and flow cytometry criteria).
timeFrame: 5 months
Other outcomes:
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Madrid
country: Spain
facility: MD Anderson Internacional España
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: MD Anderson Internacional España
name: José F Tomas, MD
role: PRINCIPAL_INVESTIGATOR
References: