Lenalidomide and Rituximab in Treating Patients With Recurrent and/or Refractory Multiple Myeloma

October 19, 2015 updated by: Memorial Sloan Kettering Cancer Center

Phase II Study of Lenalidomide and Rituximab for Patients With Relapsed and/or Refractory CD20+ Multiple Myeloma

RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with rituximab may be an effective treatment for multiple myeloma.

PURPOSE: This phase II trial is studying the side effects of giving lenalidomide together with rituximab and to see how well it works in treating patients with recurrent or refractory multiple myeloma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the safety and efficacy, as determined by response rate (complete response [CR] + near CR + partial response), of lenalidomide administered with rituximab in patients with relapsed and/or refractory CD20+ multiple myeloma.

Secondary

  • To assess the effects of this regimen on patient lymphocyte subsets (T, B, and NK cells) in peripheral blood and bone marrow samples from these patients.
  • To perform detailed phenotypic analyses of NK cells in patient blood and bone marrow samples at baseline and post-treatment.

OUTLINE: Patients receive oral lenalidomide once daily on days 1-21. Treatment with lenalidomide repeats every 28 days for at least 4 courses. Patients also receive rituximab IV once weekly in weeks 2-5 and in week 13. Patients with stable disease then receive rituximab once every 8 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Peripheral blood samples are collected at baseline, and after courses 2 and 4. Samples are examined by flow cytometry for lymphocyte subset analysis (T-, B-, and NK-cell percentages and absolute numbers) and NK-cell phenotyping (CD16, CD56, NKG2D expression). Samples are also examined by immunologic assays of isolated peripheral blood mononuclear cells. Bone marrow aspirate samples are also collected at baseline and after course 2. Bone marrow mononuclear cells are isolated and evaluated by CD138+ plasma cell selection, ex vivo antibody-dependent cellular cytotoxicity assays, and bone marrow lymphocyte subset analysis.

After completion of study therapy, patients are followed at 30 days.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2

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

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed CD20+ multiple myeloma

    • CD20+ disease defined as co-expression of CD20 on ≥ 25% of the clonal plasma cell population as defined by immunohistochemical or flow cytometric staining of a bone marrow or plasmacytoma specimen obtained at study entry

      • For flow cytometry, this is determined by calculating the frequency of CD20+ CD138+ double-positive cells within the total CD138+ plasma cell population
      • For immunohistochemistry, this is determined by dual staining for CD20 and the involved clonal light chain (kappa or lambda), with a determination of the percent double-positive (≤ 25% or ≥ 25%)
  • Symptomatic multiple myeloma that has relapsed or progressed after at least 1 prior anti-myeloma therapeutic regimen

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 16 weeks (4 months)
  • ANC ≥ 1,500/μL (unless low ANC due to multiple myeloma)
  • Platelets ≥ 100,000/μL (unless low platelets are due to multiple myeloma)
  • Serum bilirubin ≤ 2.0 mg/dL
  • AST, ALT, and alkaline phosphatase < 3 times upper limit of normal
  • Serum creatinine ≤ 2.5 mg/dL
  • Able to understand the investigational nature of lenalidomide and rituximab combination therapy and to give informed consent
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception at least 28 days before, during, and for at least 28 days after completion or discontinuation of study treatment
  • Able to take acetylsalicylic acid (ASA) (325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)
  • Prior malignancies with a disease free interval of ≥ 5 years allowed
  • No history of thromboembolic disease within the past 6 months, regardless of anticoagulation
  • No myocardial infarction within the past 6 months
  • No New York Hospital Association class III or IV heart failure
  • No uncontrolled angina
  • No severe uncontrolled ventricular arrhythmias
  • No active hepatitis B or C infection
  • No HIV 1or 2 positivity
  • No acute ischemia or active conduction system abnormalities as evidenced by ECG
  • No history of hypersensitivity reactions to lenalidomide, thalidomide, or rituximab
  • No other medical condition or laboratory evaluation that, in the treating physician's or principal investigators' opinion, makes the patient unsuitable to participate in this clinical trial
  • No concurrent active malignancy other than nonmelanoma skin cancers or carcinoma-in-situ of the cervix

PRIOR CONCURRENT THERAPY:

  • At least 3 weeks since prior therapy, including radiotherapy
  • Prior lenalidomide or thalidomide allowed
  • No prior rituximab

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: Lenalidomide and Rituximab
This study will employ a Simon optimal two-stage design. Patients will receive lenalidomide 25 mg daily for days 1-21 of each 28 day cycle. Rituximab 375 mg/m2 will be given weekly for 4 weeks beginning 1 week after the start of lenalidomide therapy (weeks 2-5), and then once 8 weeks later (week 13). Patients with stable disease or better after 4 cycles (week 16, in the absence of delays for toxicity) will be able to continue on therapy on the same lenalidomide schedule and with rituximab 375 mg/m2 given once every 8 weeks.
Other: laboratory biomarker analysis
Biological: rituximab
Other: flow cytometry
Genetic: microarray analysis
Drug: lenalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Final Response Rate After 4 Courses of Treatment
Time Frame: 2 years
2 years

Collaborators and Investigators

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

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Hani Hassoun, MD, Memorial Sloan Kettering Cancer Center

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

November 1, 2007

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

December 1, 2007

First Submitted That Met QC Criteria

December 1, 2007

First Posted (Estimate)

December 4, 2007

Study Record Updates

Last Update Posted (Estimate)

November 20, 2015

Last Update Submitted That Met QC Criteria

October 19, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Mskcc 07-070
  • P30CA008748 (U.S. NIH Grant/Contract)
  • MSKCC-07070

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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