Daratumumab, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

Inclusion Criteria:

• Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min (obtained =< 14 days prior to registration)
• Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior toregistration)
• Untransfused platelet count >= 75,000/mm^3 (obtained =< 14 days prior to registration)
• Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients withGilbert's syndrome) (obtained =< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (obtained =< 14 days prior to registration)
• Measurable disease of multiple myeloma as defined by at least ONE of the following:
• Serum monoclonal protein >= 1.0 g/dL
• >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serumimmunoglobulin kappa to lambda free light chain ratio
• Bone marrow >= 30% plasma cells
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Relapsed multiple myeloma (MM) requiring treatment who have previously received adaratumumab alone or in a daratumumab containing combination and
• Had at least a partial response to therapy, and had disease progression on orwithin 60 days of discontinuation
• At least 3 months should have elapsed since last exposure to daratumumab
• Patients must have been previously exposed to both a proteasome inhibitor and animmunomodulatory imide drug (IMiD)
• Examples of proteasome inhibitors:
• Bortezomib, carfilzomib, ixazomib, marizomib, oprozomib
• Examples of IMiD's:
• Thalidomide, lenalidomide, pomalidomide
• Negative pregnancy test done =< 7 days prior to registration, for women ofchildbearing potential only
• Willing to follow strict birth control measures
• Female patients: If they are of childbearing potential, agree to one of thefollowing:
• Practice 2 effective methods of contraception, at the same time, from thetime of signing the informed consent form through 90 days after the lastdose of study drug, AND must also adhere to the guidelines of anytreatment-specific pregnancy prevention program, if applicable, OR
• Agree to practice true abstinence when this is in line with the preferredand usual lifestyle of the subject. (Periodic abstinence [e.g., calendar,ovulation, symptothermal, post-ovulation methods] and withdrawal are notacceptable methods of contraception.)
• Male patients: even if surgically sterilized (i.e., status post-vasectomy), mustagree to one of the following:
• Agree to practice effective barrier contraception during the entire studytreatment period and through 90 days after the last dose of study drug, OR
• Must also adhere to the guidelines of any treatment-specific pregnancyprevention program, if applicable, OR lifestyle of the subject. (Periodicabstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods]and withdrawal are not acceptable methods of contraception.)
• Willing to follow the requirements of the Pomalyst Risk Evaluation and MitigationStrategy (REMS) program
• Willing to provide bone marrow and blood samples for planned research

Exclusion Criteria:

• Refractory to pomalidomide
• Concurrent amyloid light chain (AL) amyloidosis with organ involvement
• Diagnosed or treated for another malignancy =< 2 years prior to registration orpreviously diagnosed with another malignancy and have any evidence of residualdisease. NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any typeare not excluded if they have undergone complete resection
• Any of the following because this study involves an investigational agent, whosegenotoxic, mutagenic and teratogenic effects, on the developing fetus and newborn areunknown:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequatecontraception
• Other concurrent chemotherapy, or any ancillary therapy considered investigational.NOTE: Bisphosphonates are considered to be supportive care rather than therapy, andare thus allowed while on protocol treatment
• Major surgery =< 14 days prior to registration
• Evidence of current uncontrolled cardiovascular conditions, including hypertension,cardiac arrhythmias, congestive heart failure, unstable angina, or myocardialinfarction =< 6 months. Note: Prior to entry, any electrocardiogram (ECG) abnormalityat screening must be documented by the investigator as not medically relevant
• Known human immunodeficiency virus (HIV) positive
• Known hepatitis B surface antigen-positive status, or known or suspected activehepatitis C infection
• Seropositive for human immunodeficiency virus (HIV)
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surfaceantigen [HBsAg]). Subjects with resolved infection (i.e., subjects who are HBsAgnegative but positive for antibodies to hepatitis B core antigen [anti-HBc]and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screenedusing real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will beexcluded. EXCEPTION: Subjects with serologic findings suggestive of HBVvaccination (anti-HBs positivity as the only serologic marker) AND a knownhistory of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
• Seropositive for hepatitis C (except in the setting of a sustained virologicresponse [SVR], defined as aviremia at least 12 weeks after completion ofantiviral therapy)
• 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 allergies, hypersensitivity, or intolerance to corticosteroids, monoclonalantibodies or human proteins, or their excipients (refer to respective package insertsor investigator's brochure) or known sensitivity to mammalian-derived products
• Known chronic obstructive pulmonary disease with a forced expiratory volume in 1second (FEV1) < 50% of predicted normal
• Known moderate or severe persistent asthma within the past 2 years or currently hasuncontrolled asthma of any classification
• Total bilirubin =< 1.5 x ULN (except for patients with Gilbert's syndrome)