Activity & Safety Study of Lenalidomide & Rituximab as Non-chemotherapy Based Therapy on Chronic Lymphocytic Leukemia (LLC-LENAR-08)

September 27, 2013 updated by: MD Anderson International Spain SA

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28033
        • MD Anderson Internacional España
      • Salamanca, Spain, 37007
        • Hospital Clínico de Salamanca
      • Sevilla, Spain, 41013
        • Hospital Virgen del Rocío
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
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.

Other Names:
  • Lenalidomide: REVLIMID
  • Rituximab: MABTHERA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
Time Frame: 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).
5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the toxicity profile of LenRtx.
Time Frame: 5 months
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
5 months
To determine the time to treatment failure.
Time Frame: 5 months
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
5 months
To determine the molecular response rate.
Time Frame: 5 months
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
5 months
To determine the clinical response rate (combined morphological and flow cytometry criteria).
Time Frame: 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
5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MD Anderson International Spain SA

Collaborators

Celgene Corporation

Investigators

  • Principal Investigator: José F Tomas, MD, MD Anderson Internacional España

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

December 17, 2009

First Submitted That Met QC Criteria

August 18, 2010

First Posted (Estimate)

August 19, 2010

Study Record Updates

Last Update Posted (Estimate)

September 30, 2013

Last Update Submitted That Met QC Criteria

September 27, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LLC-LENAR-08 (Other Identifier: Fundación MD Anderson Internacional. España)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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