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

NCT ID: NCT01185262

Last Updated: 2013-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2013-09-30

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Recurrent and refractory chronic lymphocytic leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Lenalidomida and Rituximab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Lenalidomide: REVLIMID; Rituximab: MABTHERA

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

MD Anderson International Spain SA

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

José F Tomas, MD

Role: PRINCIPAL_INVESTIGATOR

MD Anderson Internacional España

Locations

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

Countries

Spain

Other Identifiers

LLC-LENAR-08

Identifier Type: OTHER

Identifier Source: secondary_id

LLC-LENAR-08

Identifier Type: -

Identifier Source: org_study_id

NCT01348815

Identifier Type: -

Identifier Source: nct_alias