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

NCT01185262 | Completed Phase 1

• 1 other identifier: LLC-LENAR-08
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 7

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

Outcome Measures

Primary Outcomes (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.

  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

Secondary Outcomes (4)

• To determine the toxicity profile of LenRtx.

  5 months

• To determine the time to treatment failure.

  5 months

• To determine the molecular response rate.

  5 months

• To determine the clinical response rate (combined morphological and flow cytometry criteria).

  5 months

Study Arms (1)

Lenalidomida, Rituximab

EXPERIMENTAL

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

Interventions

Lenalidomida and Rituximab 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.

Also known as: Lenalidomide: REVLIMID, Rituximab: MABTHERA

Lenalidomida, Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• MD Anderson International Spain SA: lead
• Celgene Corporation: collaborator

Study Sites (7)

Hospital Universitario Reina Sofía

Córdoba, Córdoba, 14004, Spain

Location

MD Anderson Internacional España

Madrid, Madrid, 28033, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Clínico de Salamanca

Salamanca, Salamanca, 37007, Spain

Location

Hospital Virgen del Rocío

Seville, Sevilla, 41013, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Interventions

Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• José F Tomas, MD

  MD Anderson Internacional España

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: August 19, 2010
• Study Start: April 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: September 1, 2013
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

ES (7)