Back to resultsLenalidomide and Rituximab in Treating Patients With Recurrent and/or Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma and Plasma Cell Neoplasm
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
lenalidomide
microarray analysis
flow cytometry
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring refractory multiple myeloma
Eligibility 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
Sites / Locations
- Memorial Sloan-Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lenalidomide and Rituximab
Arm Description
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.
Outcomes
Primary Outcome Measures
Final Response Rate After 4 Courses of Treatment
Secondary Outcome Measures
Full Information
NCT ID
NCT00567229
First Posted
December 1, 2007
Last Updated
October 19, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00567229
Brief Title
Lenalidomide and Rituximab in Treating Patients With Recurrent and/or Refractory Multiple Myeloma
Official Title
Phase II Study of Lenalidomide and Rituximab for Patients With Relapsed and/or Refractory CD20+ Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Why Stopped
Lack of Accrual
Study Start Date
November 2007 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
February 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma and Plasma Cell Neoplasm
Keywords
refractory multiple myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lenalidomide and Rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Intervention Type
Genetic
Intervention Name(s)
microarray analysis
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Primary Outcome Measure Information:
Title
Final Response Rate After 4 Courses of Treatment
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hani Hassoun, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Lenalidomide and Rituximab in Treating Patients With Recurrent and/or Refractory Multiple Myeloma
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