Activity & Safety Study of Lenalidomide & Rituximab as Non-chemotherapy Based Therapy on Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

— LLC-LENAR-08  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01185262
• Other study ID #: LLC-LENAR-08
• Secondary ID: LLC-LENAR-08
• Status: Completed
• Phase: Phase 1
• First received: December 17, 2009
• Last updated: September 27, 2013
• Start date: April 2009
• Est. completion date: September 2013

Study information

• Verified date: September 2013
• Source: MD Anderson International Spain SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT01348815

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: September 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

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.

Locations

Country	Name	City	State
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario La Paz	Madrid
Spain	MD Anderson Internacional España	Madrid
Spain	Hospital Clínico de Salamanca	Salamanca
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
MD Anderson International Spain SA	Celgene Corporation

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	5 months	Yes
Secondary	To determine the toxicity profile of LenRtx.	Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits	5 months	Yes
Secondary	To determine the time to treatment failure.	Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits	5 months	No
Secondary	To determine the molecular response rate.	Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits	5 months	No
Secondary	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	5 months	No