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

This study has been terminated.
(Lack of Accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00567229
First received: December 1, 2007
Last updated: April 23, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: rituximab
Drug: lenalidomide
Genetic: microarray analysis
Other: flow cytometry
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Lenalidomide and Rituximab for Patients With Relapsed and/or Refractory CD20+ Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Final response rate after 4 courses of treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pre- and post-treatment analyses of peripheral blood and bone marrow lymphocyte subsets, NK cell phenotype, and ex vivo antibody-dependent cellular cytotoxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 3
Study Start Date: November 2007
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: rituximab Drug: lenalidomide Genetic: microarray analysis Other: flow cytometry Other: laboratory biomarker analysis

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00567229

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Hani Hassoun, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Heather Landau, MD Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00567229     History of Changes
Obsolete Identifiers: NCT00590486
Other Study ID Numbers: Mskcc 07-070, P30CA008748, MSKCC-07070
Study First Received: December 1, 2007
Last Updated: April 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
refractory multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
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

ClinicalTrials.gov processed this record on July 24, 2014