A Phase II Study of Daratumumab, Clarithromycin, Pomalidomide And Dexamethasone (D-ClaPd) In Multiple Myeloma Patients Previously Exposed to Daratumumab

Inclusion Criteria:

* Histologically confirmed Multiple Myeloma
* Relapsed and/or refractory myeloma defined as follows: Relapse or progressive disease after at least one previous line of therapy which must include prior daratumumab. At least 8 doses of daratumumab in a previous line must be administered either as monotherapy or in combination with a daratumumab-free interval of ≥3 months AND patient may be daratumumab refractory defined as less than a partial remission (PR) achieved on prior daratumumab-based therapy or have exhibited progression within 60 days of receiving daratumumab. If previous therapy was autologous stem cell transplant (SCT), over 3 months must have elapsed after SCT.
* 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).
* Females of childbearing potential(FCBP) must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours of prescribing pomalidomide 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 pomalidomide. FCBP must also agree to ongoing pregnancy testing.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Able to take aspirin daily
* Life expectancy must be greater than 3 months.
* Be able to voluntarily sign and understand written informed consent.
* Absolute neutrophil count (ANC) ≥750 cells/mm3 (.75 x 109/L)
* Platelets count ≥ 50,000/mm3 (50 x 109/L)
* Serum SGOT/AST ≤ 2.0 x upper limits of normal
* Serum SGPT/ALT \<3.0 x upper limits of normal
* Serum creatinine ≤ 2.5 x upper limits of normal
* Serum total bilirubin ≤ 1.5 x upper limits of normal (Total bilirubin ≥ 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
* All participants must be registered into the mandatory POMALYST REMS™ program and be willing and able to comply with the requirements of the POMALYST REMS™ program.

Exclusion Criteria:

* Prior exposure to non-daratumumab anti-CD38 monoclonal antibodies or pomalidomide. Prior pomalidomide exposure in 1 or more previous lines of therapy allowed if partial remission (PR) or better achieved. No disease progression may have occurred within 60 days of receiving pomalidomide.
* New York Heart Association (NYHA) Class III or IV heart failure, unstable cardiac arrhythmia, or unstable angina
* Myocardial infarction within the past 6 months
* Severe obstructive airway disease
* Planned high-dose chemotherapy and autologous stem cell transplantation within 6, 28-day treatment cycles after starting on treatment
* Female patients who are lactating or have a positive serum pregnancy test during the screening period
* Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy
* Major surgery within 14 days before enrollment
* Radiotherapy within 14 days before enrollment (if area involved is small than within 7 days)
* Systemic treatment, within 14 days before the first dose, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
* Seropositive for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C
* Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
* Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
* Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
* Patient has greater than Grade 3 peripheral neuropathy, or Grade 2 pain
* Participation in other clinical trials within 30 days
* History of thromboembolic event within the past 6 months prior to enrollment