Revlimid / All-Trans Retinoic Acid (ATRA) / Dexamethasone in Relapsed/Refractory Multiple Myeloma

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form
2. Age \>/= 18 years at the time of signing the informed consent form
3. Serum creatinine \</= 2.5 mg/dl OR Creatine clearance \> 30 ml/min
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
5. Females of childbearing potential (FCBP)\* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide 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 affective 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 female of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
6. Continuation from Inclusion #5: \*A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
7. Able to take prophylactic antiplatelet/anticoagulation, warfarin or equivalent agent
8. Patient is able to understand and comply with the terms and conditions of the Lenalidomide Counseling Program.
9. Phase I Specific Inclusion Criteria: Multiple myeloma that has progressed on lenalidomide and dexamethasone combination therapy at a dose of 25 mg daily on lenalidomide and 40 mg weekly of dexamethasone with measurable levels of myeloma paraprotein in serum ( \>/= 0.5 g/dl), urine ( \>/= 0.2 g excreted in a 24-hour collection sample), or abnormal free light chain (FLC) ratio.
10. Phase I Specific Inclusion Criteria: Laboratory test results within these ranges: Absolute neutrophil count \> 1000 cells/mm\^3; Platelet count \> 100,000 cells/mm\^3 for patients with \< 50% of bone marrow plasma cells and platelet count \> 50,000 cells/mm\^3 for patients in whom \> 50% of the bone marrow nucleated cells were plasma cells; Total bilirubin \</= 2.0 mg/dL; AST (SGOT) and ALT (AGPT) \< 3 x upper limits of normal (ULN)
11. Phase II Specific Inclusion Criteria: Cohort A: Multiple myeloma that has progressed on lenalidomide and dexamethasone combination therapy with measurable levels of myeloma paraprotein in serum ( \>/= 0.5 g/dl), urine ( \>/= 0.2 g excreted in a 24-hour collection sample), or involved FLC level by more than 10 mg/dL and abnormal free light chain (FLC) ratio. Cohort B: Multiple myeloma that has progressed on single agent lenalidomide therapy with measurable disease defined as: doubling of the M-component in 2 consecutive measurements in less than or equal to 2 months OR increase in serum M-protein levels by \>/= .5g or urine protein by 200mg/24 hours, or involved FLC level by more than 10 mg/dL (with an abnormal FLC ratio).
12. Phase II Specific Inclusion Criteria: Laboratory test results within these ranges: Absolute neutrophil count \> 1000 cells/mm\^3; Platelet count \> 75,000 cells/mm\^3 for patients with \< 50% of bone marrow plasma cells and platelet count \> 50,000 cells/mm\^3 for patients in whom \> 50% of the bone marrow nucleated cells were plasma cells; Total bilirubin \</= 2.0 mg/dL; AST (SGOT) and ALT (AGPT) \< 3 x ULN

Exclusion Criteria:

1. Any serious medical condition, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
3. Use of any cancer therapy within 14 days prior to beginning cycle 1 day 1 of therapy with the exception of lenalidomide and dexamethasone (radiation therapy allowed within 5 days of completion of radiation therapy)
4. Known hypersensitivity to lenalidomide or ATRA.