This study is intended to investigate the combination of the combination of dexamethasone (Decadron®), Clarithromycin (Biaxin®), and pomalidomide (CC-4047®) [ClaPd] in multiple myeloma patients who have relapsed or refractory disease who have failed prior treatment with lenalidomide when used alone or in combination with corticosteroids. Primary endpoint will be response rate to treatment. Secondary endpoints will include toxicity of the combination, time to maximum response, and time to disease progression

This phase II study is a treatment program for patients with relapsed or refractory multiple myeloma who have had prior treatment with lenalidomide. Up to 54 patients will be enrolled. Patients who sign informed consent form and fulfill all eligibility criteria will be enrolled.

ClaPd therapy:

Dexamethasone (40mg ) on days 1, 8, 15, 22 of a 28-day cycle. Clarithromycin given orally at a dose of 500 mg twice a day on days 1-28 of a 28 day cycle.

Pomalidomide will be given 4mg daily for days 1-21 of each 28 day cycle.

Serial clinic visits and laboratory measurements will be performed to monitor for treatment response. Those patients who demonstrate progression of disease at any point during ClaPd therapy will be taken off study.

At the end of every cycle (which may coincide with day 1 of the new cycle), response and toxicity will be evaluated. During cycle 1, patients will have labwork done weekly (CBC with differential and blood electrolytes). All patients will remain on study until disease progression or side effects become excessive. Patients who achieve a stable plateau may be taken off study if eligible to proceed to high dose chemotherapy and autologous stem cell transplantation.

Inclusion Criteria:

• Subject must voluntarily sign and understand written informed consent.
• Age > 18 years at the time of signing the consent form.
• Histologically confirmed MM
• Relapsed or refractory myeloma, progression of disease either after prior therapy or lack of response to currently used therapy.
• Relapsed or progressive disease after at least 3 prior therapeutic treatments or regimens for multiple myeloma.
• Must have been previously treated with lenalidomide and has been determined to be refractory, resistant, or relapsed.
• Measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >0.1 g/dL serum free light chains, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
• Karnofsky performance status ≥70% (>60% if due to bony involvement of myeloma
• 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 and thalidomide (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 4 weeks 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 females of child bearing potential even if they have had a successful vasectomy. See Appendix V: Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods. †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).
• Able to take aspirin daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin). †
• 1ife expectancy ≥ 3 months
• Subjects must meet the following laboratory parameters:

Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) Platelets count ≥ 50,000/mm3 (75 x 109/L) Serum SGOT/AST ≤ 2.0 x upper limits of normal Serum SGPT/ALT <3.0 x upper limits of normal (ULN) Serum creatinine ≤ 2.5 x upper limits of normal Serum total bilirubin ≤ 1.5 x upper limits of normal

Exclusion Criteria:

• Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine).
• Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 5 years.
• Myocardial infarction within 6 months prior to enrollment, or NYHA(New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Known HIV infection
• Known hepatitis B or hepatitis C infection.
• Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
• Any coexisting medical problem or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial.
• Known hypersensitivity to thalidomide or lenalidomide.
• History of thromboembolic event within the past 6 months prior to enrollment.
• 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.
• 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 other experimental drug or therapy within 14 days of baseline.
• Known hypersensitivity to thalidomide or lenalidomide.
• The development of erythema nodorum if characterized by a desquamating rash while taking thalidomide, CC-4047 or similar drugs.
• Any prior use of CC-4047.
• Concurrent use of other anti-cancer agents or treatments.

121 subject signed consent; 1 subject was not considered to be evaluable and was not included in any analysis.

Adverse events were recorded from baseline until removal from study. Serious adverse events were recorded from baseline until 30 days after the last dose of study drug.

Adverse events were recorded using the CTCAE version 4.0. The adverse events listed includes serious adverse events. Serious adverse events were recorded from baseline unti