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

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
MD Anderson International Spain SA
ClinicalTrials.gov Identifier:
NCT01185262
First received: December 17, 2009
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Lenalidomida and Rituximab
Phase 1

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

Resource links provided by NLM:


Further study details as provided by MD Anderson International Spain SA:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • To determine the toxicity profile of LenRtx. [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]
    Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits

  • To determine the time to treatment failure. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits

  • To determine the molecular response rate. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits

  • To determine the clinical response rate (combined morphological and flow cytometry criteria). [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression


Enrollment: 25
Study Start Date: April 2009
Study Completion Date: September 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01185262

Locations
Spain
Hospital Universitario Reina Sofía
Córdoba, Spain, 14004
MD Anderson Internacional España
Madrid, Spain, 28033
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Clínico de Salamanca
Salamanca, Spain, 37007
Hospital Virgen del Rocío
Sevilla, Spain, 41013
Hospital Clínico Universitario de Valencia
Valencia, Spain, 46010
Hospital Universitario Miguel Servet
Zaragoza, Spain, 50009
Sponsors and Collaborators
MD Anderson International Spain SA
Celgene Corporation
Investigators
Principal Investigator: José F Tomas, MD MD Anderson Internacional España
  More Information

No publications provided

Responsible Party: MD Anderson International Spain SA
ClinicalTrials.gov Identifier: NCT01185262     History of Changes
Obsolete Identifiers: NCT01348815
Other Study ID Numbers: LLC-LENAR-08, LLC-LENAR-08
Study First Received: December 17, 2009
Last Updated: September 27, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by MD Anderson International Spain SA:
Recurrent and refractory chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Thalidomide
Lenalidomide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 14, 2014