Lenalidomide Intensification in Patients With Serologic/Asymptomatic Progression of Multiple Myeloma While on Lenalidomide Maintenance

Inclusion Criteria:

- Patients must be 18 years of age or above at the time of enrollment.

- Patients must show evidence of asymptomatic relapse and/or progression of disease
(increasing M spike in serum or urine by consensus criteria) while on lenalidomide
maintenance after HDM/ASCT as part of initial line of therapy.

- Patients who have not had an HDM/ASCT as part of initial line of therapy but who are
on continuous/maintenance lenalidomide after initial therapy will be permitted on
study.

- Patient must have myeloma that is measurable by either serum or urine evaluation of
the monoclonal component or by assay of serum free light chains. Measurable disease
is defined as one or more of the following: serum M-protein ≥ to 0.5 g/dl, urine
M-protein ≥ 200 mg/24 h, and/or serum FLC assay: involved FLC level > 10 mg/dL with
abnormal serum FLC ratio.

- Patients must have adequate organ function including: Hepatic function with Bilirubin
<2x the upper limit of normal and ALT and AST < 3 x the upper limit of normal; renal
function with creatinine clearance ≥ 60 ml/min using the Cockcroft-Gault formula;
hematologic function as defined by an absolute neutrophil count > 1000 neutrophils
per microliter, platelet > 50,000 platelets per microliter and hemoglobin of ≥ 9
gm/dL without transfusion support

- All study participants must be registered into the mandatory Revlimid REMS® program,
and be willing and able to comply with the requirements of the REMS® program.

- Females of child bearing potential (FCBP) must adhere to the scheduled pregnancy
testing as required in the Revlimid REMS® program

- FCBP must have a negative serum or urine pregnancy test with a sensitivity of at
least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing
lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either
commit to continued abstinence from heterosexual intercourse or begin TWO acceptable
methods of birth control, one highly effective method and one additional effective
method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP
must also agree to ongoing pregnancy testing. Men must agree to use a latex condom
during sexual contact with a FCBP even if they have had a successful vasectomy. See
Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth
Control Methods.

Exclusion Criteria:

- Patients with symptomatic relapse and/or progression of multiple myeloma. (Appendix
A).

- Patients with plasma cell leukemia.

- Karnofsky performance score less than 70% or ECOG performance status greater than 2.

- Patients with uncontrolled bacterial, viral or fungal infections (currently taking
medication and progression of clinical symptoms).

- Patients with prior malignancies except resected basal cell carcinoma or treated
cervical carcinoma in situ or other cancer treated with curative intent > 5 years
previously. Cancer treated with curative intent < 5 years previously will not be
allowed unless approved by the Protocol Chairs.

- Female patients who are pregnant (positive HCG) or breastfeeding. (Lactating females
must agree not to breast feed while taking lenalidomide)

- Patients seropositive for the human immunodeficiency virus (HIV).

- Prior organ transplant requiring immunosuppressive therapy.

- Patients who were previously exposed to higher doses of lenalidomide and who
developed severe adverse events at higher doses that preclude incremental dosing.