Thalidomide to Overcome Lenalidomide Resistance After Autologous Hematopoietic Stem Cell Transplantation (HCT)

Inclusion Criteria:

1. Patient or legally authorized representative able to sign an informed consent form.
2. Age 18 years old or older.
3. Multiple myeloma showing signs of biochemical progression while taking lenalidomide or lenalidomide plus dexamethasone maintenance therapy after autologous hematopoietic stem cell transplantation. (Progression is defined solely based on serum or urine M-protein, or in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved serum free light chain level -- please also see appendix E for full details.)
4. Patients with biochemical progression only with at least \>/= 25% increase from the baseline in any of the following parameters on at least 2 occasions; and when the treating physician deems a change in therapy is necessary: a. Serum M-protein; b. Urine M-protein; or, c. In patients without measureable serum and urine M-protein levels; the difference between involved and uninvolved free light chain levels.
5. Lenalidomide must have been used for at least 6 months after autologous hematopoietic stem cell transplantation with the current dose of Lenalidomide 15 mg/day or less.
6. Serum creatinine clearance (Cockcroft-Gault Equation) \>= 50 mL/minute.
7. Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology Group (ECOG).
8. Patients must be informed of the Celgene Risk Management Program and mandatory registration as well as be willing and able to comply with its requirements.
9. Negative Beta Human Chorionic Gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to ongoing pregnancy testing while on treatment with lenalidomide.
10. Woman with child bearing potential 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.
11. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
12. Laboratory test results within these ranges: a. Absolute neutrophil count \> 1000 cells/mm3. b. Platelet count \> 50,000 cells/mm3 for patients with \< 50% of bone marrow plasma cells OR platelet count \> 25,000 cells/mm3 for patients in whom \> 50% of the bone marrow nucleated cells were plasma cells. c. Total bilirubin \</= 2.0 mg/dL. d. AST (SGOT) and ALT (AGPT) \</= 3 x upper normal limit.
13. Able to take anticoagulation, warfarin or equivalent agent, as detailed in the treatment plan.
14. HIV negative.

Exclusion Criteria:

1. Any serious medical condition or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Patients with symptomatic relapse, including those with new bone lesions, soft tissue plasmacytomas, an increase in the size of existing bone lesions or soft tissue plasmacytomas, decrease in hemoglobin, rise in serum creatinine or hypercalcemia.
3. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
4. Known hypersensitivity to thalidomide or lenalidomide.
5. Known history of resistance to Thalidomide.
6. Patients with grade III-IV neuropathy.