Inclusion Criteria

Inclusion

- Understand and voluntarily sign an informed consent form

- Age ≥18 years at the time of signing the informed consent form

- Able to adhere to the study visit schedule and other protocol requirements

- Refractory or relapsed multiple myeloma

- Measurable disease defined as at least one of the following: Serum m-spike >= 1g/dL,
urine m-spike >= 200mg/24hrs, serum free light chains >= 100mg/L (provided the
kappa/lambda ratio is abnormal), or bone marrow plasma cells >= 30%

- Previous therapy with IMiD™ compounds (thalidomide, lenalidomide, pomalidomide),
proteasome inhibitors (bortezomib, carfilzomib), and corticosteroids must be
discontinued at least 14 days before entry onto this study.

- Previous cytotoxic chemotherapy (e.g. alkylating chemotherapy, anthracyclines, and
vinca alkaloids), radiation therapy to the pelvis, and any experimental therapy other
than carfilzomib or pomalidomide must have been discontinued at least 28 days prior
to entry onto this study.

- ECOG performance status of ≤ 2 at study entry (see Appendix II).

- Laboratory test results within these ranges:

- Absolute neutrophil count ≥ 1,500 /mm³

- Platelet count ≥ 75,000/mm³

- Calculated creatinine clearance (Cockroft-Gault) ≥ 30ml/min.

- Total bilirubin ≤ 1.5 x ULN

- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase
[AST]) and serum glutamic-pyruvic transaminase (SGPT) (alanine
aminotransferase [ALT]) levels ≤2 x ULN

- Disease-free of prior malignancies for ≥ 5 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
or breast.

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

- Females of childbearing potential (FCBP)must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again
within 24 hours of prescribing lenalidomide (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.

- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to ASA may use warfarin or low molecular weight heparin) if no additional
risk factor for VTE other than myeloma diagnosis according to IMW guidelines

- Able to take low molecular weight heparin or warfarin if >1 additional risk factor
for VTE according to IMW guidelines

Exclusion

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form

- Pregnant or breast feeding females (Lactating females must agree not to breast feed
while taking lenalidomide or azacitidine)

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study

- Use of any experimental drug or therapy other than carfilzomib and pomalidomide
within 28 days of treatment start on this protocol.

- Neuropathy > Grade 2

- Known hypersensitivity to thalidomide, lenalidomide, azacitidine, or mannitol

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or lenalidomide drugs

- Concurrent use of other anti-cancer agents or treatments, concurrent radiation to the
pelvis. Palliative radiation to areas outside the pelvis is allowed

- Known positive for HIV or infectious hepatitis, type B or C

- Previous inability to tolerate full-dose lenalidomide, adjusted to creatinine
clearance (CrCl) according to Cockroft-Gault at the time of previous lenalidomide
treatment (25mg day 1-21 every 28 days if CrCl > 60ml/min, 10mg lenalidomide d1-21
every 28 days if CrCl < 60mL/min but > 30mL/min, lenalidomide 15mg every 48 h d1-21
every 28 days if CrCl < 30mL/min but not requiring dialysis, lenalidomide 5mg daily,
day 1-21 every 28 days if CrCl < 30mL/min and requiring dialysis).