Intervention: Lenalidomide
Trial phase: Phase 2
ATC code: L04AX04
SMILES: Nc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 3
Group 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.
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