STEP I: Patients must have measurable or evaluable disease as defined by having one or more of the following, obtained within 28 days prior to randomization:\r\n* >= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis\r\n* >= 200 mg/24 hours (hrs) of monoclonal protein on a 24 hour urine protein electrophoresis\r\n* Involved free light chain >= 10 mg/dL or >= 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)\r\n* Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)\r\n* Serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and serum free light chain (FLC) assay are required to be performed within 28 days prior to randomization; a bone marrow biopsy and/or aspirate is required within 28 days if bone marrow is being followed for response\r\n** NOTE: UPEP (on a 24-hour collection) is required, no substitute method is acceptable; urine must be followed monthly if the baseline urine M-spike is >= 200 mg/24 hr; please note that if both serum and urine M-components are present, both must be followed in order to evaluate response\r\n** NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine; measurable disease in the serum is defined as having a serum M-spike >= 1 g/dL; measurable disease in the urine is defined as having a urine M-spike >= 200 mg/24 hrXx_NEWLINE_xXParticipants must have disease that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains or by minimal residual detection; measurable disease is defined as one or more of the following:\r\n* Serum M protein > 0.5 G/DL, or\r\n* Urine M protein > 200 MG/24H, and/or\r\n* Serum free light chain (FLC) assay: involved FLC level > 10 MG/DL with abnormal serum FLC ratio\r\n* >= 50 plasma cells detectable by multicolor flow cytometry, at a sensitive level of 10^-4 (determined by central review)Xx_NEWLINE_xXPatient must have measurable disease or non-measurable disease, defined as one or more of the following holding true:\r\n* Measurable disease:\r\n** Serum M-protein >= 1.0 g/dL (>= 0.5 g/dL for IgA or IgM myeloma) and/or\r\n** Urine M-protein >= 200 mg/24 hours and/or\r\n** Involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio\r\n* For non-measurable disease:\r\n** Baseline marrow burden of myeloma of at least 30%Xx_NEWLINE_xXRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patient must have measurable disease or non-measurable disease after progression on pomalidomide + dexamethasone, defined as one or more of the following holding true:\r\n* Measurable disease:\r\n** Serum M-protein >= 0.5 g/dL and/or\r\n** Urine M-protein >= 200 mg/24 hours and/or\r\n** Involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio\r\n* For non-measurable disease:\r\n** Marrow burden of myeloma of at least 30%Xx_NEWLINE_xXInclusion criteria:\n\n        Part A\n\n          -  Patients must have a known diagnosis of multiple myeloma (MM) with evidence of\n             measurable disease, as defined below, and have evidence of disease progression based\n             on International Myeloma Working Group (IMWG) criteria:\n\n          -  Serum M-protein ?1g/dL, or urine M-protein ?200 mg/24 hours, OR\n\n          -  In the absence of measurable M-protein, serum immunoglobulin free light chain ?10\n             mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio.\n\n          -  Patients must have received at least 3 prior lines of therapy for MM and must include\n             treatment with an immunomodulatory drug (IMiD) (for ?2 cycles or ?2 months of\n             treatment) and a proteasome inhibitor (for ?2 cycles or ?2 months of treatment).\n             Induction therapy and stem cell transplant (± maintenance) will be considered as one\n             regimen within a line, OR\n\n          -  Patients whose disease is double refractory to an IMiD and a proteasome inhibitor. For\n             patients who have received more than one type of IMiD and proteasome inhibitor, their\n             disease must be refractory to the most recent one.\n\n          -  Patients must have achieved a minimal response (MR) or better to at least one prior\n             line of therapy.\n\n          -  Patients must have received an alkylating agent (for ?2 cycles or ?2 months of\n             treatment) either alone or in combination with other MM treatments (history of stem\n             cell transplant is acceptable). Treatment with high-dose Melphalan for stem cell\n             transplantation meets this requirement.\n\n          -  Signed written informed consent and be willing and able to complete all study-related\n             procedures.\n\n        Part B\n\n          -  Patients must have a known diagnosis of multiple myeloma (MM) with evidence of\n             measurable disease, as defined below, and have evidence of disease progression based\n             on International Myeloma Working Group (IMWG) criteria:\n\n          -  Serum M-protein ?1g/dL, or urine M-protein ?200 mg/24 hours, OR\n\n          -  In the absence of measurable M-protein, serum immunoglobulin free light chain ?10\n             mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio.\n\n          -  Patients must have received at least 3 cycles of daratumumab treatment with at least 6\n             weeks from the last treatment with daratumumab to the first study treatment OR at\n             least 2 cycles of daratumumab treatment in case another therapy is given between\n             daratumumab and isatuximab with at least 12 weeks from the last treatment with\n             daratumumab to the first study treatment.\n\n          -  Patients must have achieved MR or better to at least 1 prior line of therapy.\n\n          -  Signed written informed consent and be willing and able to complete all study-related\n             procedures.\n\n        Exclusion criteria:\n\n          -  Patients <18 years old.\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status >2.\n\n          -  Poor bone marrow reserve.\n\n          -  Poor organ function.\n\n          -  Known intolerance/hypersensitivity to IMiDs, dexamethasone, boron or mannitol,\n             sucrose, histidine, or polysorbate 80.\n\n          -  Any serious active disease (including clinically significant infection that is\n             chronic, recurrent, or active) or comorbid condition, which, in the opinion of the\n             Investigator, could interfere with the safety, the compliance with the study, or with\n             the interpretation of the results.\n\n          -  Any severe underlying medical conditions including presence of laboratory\n             abnormalities, which could impair the ability to participate in the study or the\n             interpretation of its results.\n\n        The above information is not intended to contain all considerations relevant to a patient's\n        potential participation in a clinical trial.Xx_NEWLINE_xXInclusion criteria:\n\n        Phase 1:\n\n          -  For dose escalation cohorts, patients with confirmed selected CD38+ hematological\n             malignancies as specified below who have progressed on after standard therapy or for\n             whom there is no effective standard therapy (refractory/relapsed patients). B-cell\n             Non-Hodgkin-lymphoma/leukemia (NHL) patients having at least 1 measurable lesion.\n             Multiple myeloma (MM) patients with measurable M-protein serum and/or 24-hour urine.\n             Acute myeloid leukemia (AML) patients, all types except M3 based on\n             French-American-British (FAB) classification. Acute Lymphoblastic Leukemia (B-cell\n             ALL) patients. Chronic lymphocytic leukemia (CLL) patients.\n\n          -  For expansion cohorts, patients with relapsed/refractory MM with measurable M-protein\n             (serum M-protein of >0.5 g/dL and/or urine M-protein of >200 mg (24-hr urine)) or\n             elevated serum free light chains (FLC) >10 mg/dL with abnormal FLC ratio) who have\n             progressed on or after standard therapy that includes an iMiD and a proteasome\n             inhibitor and who meet the protocol defined criteria for standard risk or high risk.\n\n        Phase 2:\n\n          -  Patients must have a known diagnosis of multiple myeloma with evidence of measurable\n             disease, and have evidence of disease progression based on International Myeloma\n             Working Group (IMWG) criteria: Serum M-protein ?1 g/dL, or urine M-protein ?200 mg/24\n             hours or in the absence of measurable m-protein, serum FLC ?10 mg/dL, and abnormal\n             serum immunoglobulin kappa lambda FLC ratio (<0.26 or >1.65).\n\n          -  Patients must have received at least three prior lines of therapy for MM and must\n             include treatment with an Immunomodulatory drug (IMiD) (for ?2 cycles or ?2 months of\n             treatment) and a proteasome inhibitor (PI) (for ?2 cycles or ?2 months of treatment)\n             OR patients whose disease is double refractory to an IMiD and a PI. For patients who\n             have received more than 1 type of IMiD and PI, their disease must be refractory to the\n             most recent one.\n\n          -  Patients must have achieved a minimal response or better to at least one prior line of\n             therapy.\n\n          -  Patients must have received an alkylating agent (?2 cycles or ?2 months) either alone\n             or in combination with other MM treatments.\n\n          -  Stage 2 only: Patients must have evidence of disease progression on or after the most\n             recent prior regimen based on IMWG criteria.\n\n        Exclusion criteria:\n\n        Phase 1:\n\n          -  Karnofsky performance status <60\n\n          -  Poor bone marrow reserve\n\n          -  Poor organ function\n\n          -  Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or\n             known hypersensitivity to any of the components of the study therapy that is not\n             amenable to pre-medication with steroids and H2 blockers\n\n          -  Any serious active disease (including clinically significant infection that is\n             chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the\n             investigator, could interfere with the safety, the compliance with the study or with\n             the interpretation of the results\n\n          -  Any severe underlying medical conditions including presence of laboratory\n             abnormalities, which could impair the ability to participate in the study or the\n             interpretation of its results\n\n        Phase 2:\n\n          -  Patients with multiple myeloma immunoglobulin M (IgM) subtype\n\n          -  Previous treatment with any anti-CD38 therapy\n\n          -  Patients with concurrent plasma cell leukemia\n\n          -  Patients with known or suspected amyloidosis\n\n          -  Karnofsky performance status <60 (stage 1)/ECOG Performance status >2 (stage 2).\n\n          -  Poor bone marrow reserve\n\n          -  Poor organ function\n\n          -  Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or\n             known hypersensitivity to any of the components of the study therapy that is not\n             amenable to pre-medication with steroids and H2 blockers\n\n          -  Any serious active disease (including clinically significant infection that is\n             chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the\n             investigator, could interfere with the safety, the compliance with the study or with\n             the interpretation of the results\n\n          -  Any severe underlying medical conditions including presence of laboratory\n             abnormalities, which could impair the ability to participate in the study or the\n             interpretation of its results\n\n        The above information is not intended to contain all considerations relevant to a patient's\n        potential participation in a clinical trial.Xx_NEWLINE_xXSerum M-Protein >=1.0 g/dL (>=10 g/L), ORXx_NEWLINE_xXSerum free light chain (FLC) >= 10 mg/dL, provided serum FLC ratio is abnormal in participants who do not have measurable disease by Serum Protein Electrophoresis (SPEP) or Urine Protein Electrophoresis (UPEP) criteria.Xx_NEWLINE_xXSerum M- protein ?0.5 g/dL for IgG, IgM, IgA, or ?0.05 g/dL for IgD; orXx_NEWLINE_xXSerum free light chain (FLC) assay: involved FLC level ?10 mg/dL and an abnormal serum FLC ratio (<0.26 or >1.65).Xx_NEWLINE_xXSerum monoclonal protein ? 0.5 g/dL by protein electrophoresis.Xx_NEWLINE_xXSerum free light chain ? 10 mg/dL AND abnormal serum kappa to lambda free light chain ratioXx_NEWLINE_xXPatients must have measurable disease according to International Myeloma Working Group (IMWG) criteria; measurable disease includes at least one of the following criteria:\r\n* Serum M-protein >= 1.0 g/dL, and/or\r\n* Urine M-protein >= 200 mg/24 hours, and/or\r\n* Involved serum free light chain >= 10 mg/dL (>= 100 mg/L) AND an abnormal serum free light chain ratio, and/or\r\n* Baseline marrow burden or myeloma of at least 30%Xx_NEWLINE_xXDisease that has progressed during or within 6 months of coming off therapy with bortezomib and lenalidomide (either sequentially or concurrent); progressive disease is defined as any of the following:\r\n* An increase of >= 25% from lowest response value in any of the following:\r\n** Serum M-protein (absolute increase must be >= 0.5 g/dL) AND/OR\r\n** Urine M-protein (absolute increase must be >= 200 mg/24 hours) AND/OR\r\n** For patients without a measurable serum or urine M-protein but measurable disease by serum free light chain testing: Difference between the involved and uninvolved serum free light chain level (absolute increase must be >= 10 mg/dL) AND/OR\r\n** For patients without a measurable serum or urine M-component or serum free light chain level: % marrow involvement with myeloma (absolute increase must be >= 10%) AND/OR\r\n* Definite development of new bone lesions or extramedullary plasmacytomas or definite increase in the size of existing bone lesions or extramedullary plasmacytomas AND/OR\r\n* Hypercalcemia (corrected serum calcium > 11.5 mg/dL) attributable to myeloma (e.g. not due to omitted doses of biophosphonate)Xx_NEWLINE_xXPatients must have measurable disease defined as at least one of the following:\r\n* Serum M-protein >= 0.5 g/dl (>= 5 g/l)\r\n* Urine M-protein >= 200 mg/24 hours (h)\r\n* Serum free light chain (FLC) assay: involved FLC level >= 10 mg/dl (>= 100 mg/l) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)\r\n* Quantitative immunoglobulin > 500 mg/dL, only for immunoglobulin (Ig)A and IgD myeloma when the protein electrophoresis under-represents disease burden\r\n* Biopsy proven plasmacytoma > 1x1 cm (should be measured within 28 days prior to initial investigational agent dosing)Xx_NEWLINE_xXMeasurable disease defined by any of following: Serum M-protein > 1 g/dL; Urine M-protein > 200 mg/24h; Serum free light chain (FLC) assay: involved FLC level > or equal to 10 mg/dL provided serum FLC ratio is abnormal; subjects who are non-secretors will be considered on a case-by-case basisXx_NEWLINE_xXMeasurable serum and/or urine M-protein from prior to induction therapy documented and available; a positive serum free lite assay is acceptableXx_NEWLINE_xXMeasurable disease, as indicated by one or more of the following:\r\n* Serum myeloma protein (M-protein) >= 0.5 g/dL\r\n* Urine M-protein >= 200 mg/24 hours\r\n* If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable\r\n* Involved serum free light chains >= 10 mg/dL provided that free light chain ratio is abnormalXx_NEWLINE_xXMeasurable disease, as indicated by one or more of the following: Serum M-protein ? 0.5 g/dL Urine Bence Jones protein ? 200 mg/24 hr Elevated Free Light Chain as per IMWG criteria, and abnormal ratioXx_NEWLINE_xXLight chain multiple myeloma (MM), for participants without measurable disease in the serum or urine: serum Immunoglobulin (Ig) free light chain (FLC) >= 10 mg/dL and abnormal FLC ratioXx_NEWLINE_xXMeasureable disease, as defined by at least one of the following: serum M protein 0.5 g/dL or higher, urine M protein 200 mg/24 hour or higher, and serum immunoglobulin free light chain 10 mg/dL or higher and abnormal serum immunoglobulin kappa lambda free light chain ratioXx_NEWLINE_xXKey Inclusion Criteria:\n\n        Individuals eligible to participate in this study must meet the following key criteria and\n        additional criteria as specified in the protocol:\n\n          1. Male or female, aged ? 18 years\n\n          2. Confirmed diagnosis of MM per IMWG criteria\n\n          3. Measurable disease as defined by one or more of the following:\n\n               -  Serum M-protein ? 0.5 g/dL\n\n               -  Urine M-protein ? 200 mg/24 hours\n\n               -  Serum Free Light Chain (FLC) assay: involved FLC level ? 10 mg/dL provided serum\n                  FLC ratio is abnormal\n\n               -  In cases where SPEP is unreliable, serum quantitative immunoglobulin (qIgA) ? 750\n                  mg/dL (0.75 g/dL) is acceptable\n\n          4. Relapsed or refractory (Rajkumar, 2011) to 3 or more different prior lines of therapy\n             for MM, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs),\n             chemotherapies, or monoclonal antibodies, and not a candidate for, or intolerant to\n             established therapy known to provide clinical benefit.\n\n          5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1\n\n          6. Adequate organ and marrow function at Screening, as defined by the study protocol.\n\n        Key Exclusion Criteria:\n\n          1. Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma,\n             Waldenstrom's macroglobulinemia, or IgM myeloma\n\n          2. Active plasma cell leukemia (? 2.0 × 109/L circulating plasma cells by standard\n             differential)\n\n          3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and\n             skin changes)\n\n          4. Prior treatment directed to B-cell Activating Factor (BAFF; BLyS), B-cell Maturation\n             Antigen (BCMA;TNFSF17) or Transmembrane Activator and CAML interactor (TACI;\n             TNFSF13B), including antibodies or BCMA- or TACI-directed Chimeric Antigen Receptor\n             (CAR)-T cell therapyXx_NEWLINE_xXHigh-risk MGUS: must have < 10% plasma cells and < 3.0g/dL M-spike and at least 3 of the following 5 criteria:\r\n* Abnormal free light-chain (FLC) ratio (< 0.26 or > 1.65)\r\n* M-protein concentration (>= 1.5 g/dL)\r\n* Reduction of =< 2 non-involved immunoglobulin isotype levels (immunoparesis)\r\n* Abnormal ratio of plasma cells in the bone marrow > 95%\r\n* Non-IgG M protein (including IgA)Xx_NEWLINE_xXPatient with purely non-secretory multiple myeloma [absence of monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by the use of conventional electrophoresis and immunofixation techniques and the absence of involved serum free light chain >100 mg/L].Xx_NEWLINE_xXSerum M-protein defined by the following:Xx_NEWLINE_xXIgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ?1.0 g/dL (measured by protein electrophoresis [PEP]);Xx_NEWLINE_xXSerum free light chain (FLC) ?10 mg/dL with abnormal ratio in subjects with unmeasurable disease by serum or urine PEP.Xx_NEWLINE_xXMust meet criteria of high-risk smoldering multiple myeloma (MM) based on the criteria described below:\r\n* Definition of high-risk smoldering multiple myeloma (SMM):\r\n** Bone marrow clonal plasma cells >= 10% and =< 60% and any one or more of the following:\r\n*** Serum M protein >= 3.0 g/dL (immunoglobulin [Ig]A, IgG, IgM, or IgD)\r\n*** IgA SMM\r\n*** Immunoparesis with reduction of two uninvolved immunoglobulin isotypes\r\n*** Serum involved/uninvolved free light chain ratio >= 8 (but less than 100)\r\n**** Free light chain smoldering myeloma patients are not excluded\r\n*** Progressive increase in M protein level (evolving type of SMM)\r\n**** Increase in serum monoclonal protein by >= 10% on two successive evaluations within a 6 month period\r\n*** Bone marrow clonal plasma cells 50-60%\r\n*** Abnormal plasma cell immunophenotype (>= 95% of bone marrow plasma cells are clonal) and reduction of one or more uninvolved immunoglobulin isotypes\r\n*** t (4;14) or del 17p or 1q gain\r\n*** Increased circulating plasma cells\r\n*** Magnetic resonance imaging (MRI) with diffuse abnormalities or 1 focal lesion\r\n*** Positron emission tomography (PET)-computed tomography (CT) with one focal lesion with increased uptake without underlying osteolytic bone destruction\r\n*** Urine monoclonal light chain excretion >= 500 mg/24 hoursXx_NEWLINE_xXNo evidence of hypercalcemia, renal failure, anemia, and bone lesions (CRAB) criteria or new criteria of active MM which including the following:\r\n* Increased calcium levels (corrected serum calcium > 0.25 mmol/dL above the upper limit of normal or > .275 mmol/dL) related to MM\r\n* Renal insufficiency (attributable to MM)\r\n* Anemia (hemoglobin [Hb] 2 g/dL below the lower limit of normal or < 10 g/dL) related to MM\r\n* Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)\r\n* Bone marrow plasma cells > 60%\r\n* Serum involved/uninvolved free light chain (FLC) ratio >= 100, provided the absolute level of the involved free light chain is at least 100 mg/L and repeated twice\r\n* MRI with two or more focal lesion that is at least 5 mm or greater in size\r\n** Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligibleXx_NEWLINE_xXPatients must have measurable disease defined by at least 1 of the following measurements:\r\n* Serum M-protein >= 1.0 g/dL (>= 10 g/L) for an immunoglobulin (Ig)G myeloma, >= 0.1 g/dL for an IgD myeloma or 0.5 g/dL (>= 5g/L) for an IgA myeloma\r\n* Urine light chain >= 200 mg/24 hours\r\n* Serum free light chain >= 10 mg/dL provided the free light chain (FLC) ratio is abnormal\r\n* Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosis on aspirationXx_NEWLINE_xXMeasurable disease at the time of relapse, defined as a monoclonal immunoglobulin spike on serum electrophoresis of >= 1 gm/dL (immunoglobulin [IG]G) or >= 0.5 gm/dL (IGA) and/or urine monoclonal immunoglobulin spike of > 200 mg/24 hours and/ or involved free light chain (FLC) level >= 10 mg/dl and the serum FLC ratio is abnormalXx_NEWLINE_xXPatients must have measurable disease defined as any of the following:\r\n* Serum monoclonal protein >= 500 mg/dL by protein electrophoresis \r\n* > 200 mg of monoclonal protein in the urine on screening 24-hour electrophoresis \r\n* Serum immunoglobulin free light chain >= 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXCOHORT B ONLY: serum immunoglobulin free light chain >= 5 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXMeasurable disease at Screening: Serum monoclonal protein of at least 1.0 g/dL (10g/L) by protein electrophoresis or at least 200 mg of monoclonal protein in the urine on 24-hr electrophoresis or serum immunoglobulin free light chain of at least 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio.Xx_NEWLINE_xXInvolved/un-involved light chain ratio must be < 100Xx_NEWLINE_xXMeasurable disease within the past 4 weeks defined by any one of the following:\r\n* Serum monoclonal protein >= 1.0 g/dl\r\n* Urine monoclonal protein > 200 mg/24 hour\r\n* Serum immunoglobulin free light chain > 10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)\r\n* NOTE: As of Amendment L, the primary endpoint is MRD(-) CR rate; therefore, per the discretion of the principal investigator, patients without measurable disease (e.g., M-spike < 1) may also be enrolled; this is in line with the most recent International Myeloma Working Group Multiple Myeloma (IMWG MM) response criteriaXx_NEWLINE_xXMeasurable disease defined by at least one of the following:\r\n* Serum monoclonal protein (serum protein electrophoresis [SPEP]) > 1gm/dL\r\n* Serum free light chain (sFLC): involved free light chain (FLC) >= 10mg/dL AND abnormal kappa to lambda serum free light chain ratio\r\n* >= 200mg of monoclonal protein in the urine on 24 hour electrophoresis (urine protein electrophoresis [UPEP])Xx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein ? 1.0 g/dL\r\n* ? 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain ? 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXHave measurable disease by International Myeloma Working Group (IMWG) criteria based on one or more of the following findings:\r\n* Serum monoclonal immunoglobulin (M-protein) ? 1 g/dL\r\n* Urine M-protein ? 200 mg/24 hour\r\n* Involved serum free light chain (sFLC) level ? 10 mg/dL with abnormal kappa/lambda ratio\r\n* Measurable biopsy-proven plasmacytomas (? 1 lesion that has a single diameter ? 2 cm)\r\n* Bone marrow plasma cells ? 30%Xx_NEWLINE_xXSerum M-protein > 0.5 g/dLXx_NEWLINE_xXSerum free light chain assay: involved free light chain level > 10 mg/dL (> 100 mg/L) provided the serum free light chain ratio is abnormalXx_NEWLINE_xXInclusion Criteria:\n\n          1. Subjects must be ? 18 years of age at the time of screening.\n\n          2. Subjects must have a confirmed diagnosis of relapsed/refractory MM as per IMWG\n             criteria (Rajkumar et al, 2014) or intolerant to all established regimens with proven\n             clinical benefit, which include agents from the following 3 classes of anti myeloma\n             therapies: PIs, IMIDs, and mAbs and have measurable disease with at least one of the\n             following criteria:\n\n               1. Serum M-protein ? 0.5 g/dL\n\n               2. Urine M-protein ? 200 mg/24 hours\n\n               3. Serum free light chain (FLC) assay: involved FLC level ? 10 mg/dL provided serum\n                  FLC ratio is abnormal.\n\n          3. Subjects must either be ineligible for or post-autologous stem cell transplant.\n\n          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n\n          5. Adequate organ and marrow functions as determined per protocol-defined criteria.\n\n        Exclusion Criteria\n\n        Any of the following would exclude the subject from participation in the study:\n\n        Target Disease Exceptions:\n\n          1. Subjects who have previously received an autologous stem cell transplant if less than\n             90 days have elapsed from the time of transplant or the subject has not recovered from\n             transplant associated toxicities prior to the first scheduled dose of MEDI2228\n\n          2. Subjects who have previously received an allogeneic stem cell transplant\n\n          3. Central nervous system (CNS) disease (including meningeal involvement) by MRI or\n             cerebrospinal fluid exam\n\n          4. Known history of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein,\n             skin changes (POEMS) syndrome, plasma cell leukemia, Waldenstrom's macroglobulinemia,\n             or amyloidosis\n\n             Medical History and Concurrent Diseases:\n\n          5. Any condition that, in the opinion of the investigator, would interfere with\n             evaluation of the investigational product or interpretation of subject safety or study\n             resultsXx_NEWLINE_xXSerum monoclonal protein ? 0.5 g/dL by serum protein electrophoresis (SPEP)Xx_NEWLINE_xXSerum free light chain (SFLC) ? 10 mg/dL AND abnormal serum kappa to lambda free light chain ratioXx_NEWLINE_xXPatients with multiple myeloma who demonstrate evidence of serologic relapse/progression while on lenalidomide maintenance given as part of first line therapy (including upfront high-dose chemotherapy followed by autologous hematopoietic cell transplantation [HCT]) without symptomatic relapse/progression.\r\n* Lenalidomide maintenance is defined as single agent lenalidomide therapy of any doses up to 10 mg PO daily for 14-28 days (28-day cycle). Relapse/progression is defined as increase of 25% from lowest confirmed response value in one or more of the following criteria:\r\n** Serum M –protein (absolute increase must be >= 0.5g/dl)\r\n** Serum M-protein increase > 1g/dl, if the lowest M component was > 5 g/dl\r\n** Urine M –protein (absolute increase must be > 200 mg in 24 hours)\r\n** In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be > 10 mg/dl)\r\n * For patients relapsing from complete remission, relapse is defined as: reappearance of serum or serum M-protein by immunofixation or electrophoresisXx_NEWLINE_xXMeasurable disease with at least 1 of the following assessed within 21 days prior to cycle 1 day 1: \r\n* Serum M-protein >= 0.5 g/dL\r\n* Urine M-protein >= 200 mg/24 hour\r\n* In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 10 mg/dL (involved light chain) and an abnormal serum kappa lambda ratioXx_NEWLINE_xXPatients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques and the absence of involved serum free light chain >100 mg/L]. Patients with light chain MM detected in the serum by free light chain assay are eligible.Xx_NEWLINE_xXHave measurable disease by International Myeloma Working Group (IMWG) criteria based on one or more of the following findings:\r\n* Serum M-protein >= 1 g/dL\r\n* Urine M-protein >= 200 mg/24 hour\r\n* Involved serum free light chain (sFLC) level >= 10 mg/dL with abnormal ?/? ratio\r\n* Measurable biopsy-proven plasmacytomas (>= 1 lesion that has a single diameter >= 2 cm)\r\n* Bone marrow plasma cells >= 30%Xx_NEWLINE_xXPatients with evidence of progression, relapse or refractory disease from last line of therapy as defined by International Myeloma Working Group (IMWG) criteria; a line of therapy is defined as one or more cycles of a planned treatment program which may be one therapy or a sequence of treatments; a new line of therapy begins when a planned course of therapy is modified due to disease progression, relapse or toxicity or when a planned period of observation off therapy; measurable disease as defined by any of the following:\r\n* Serum M-protein >= 0.5 g/dl (>= 10 g/l)\r\n* Urine monoclonal protein >= 200 mg/24 hour(h)\r\n* Involved free light chain (FLC) level >= 10mg/dl (>= 100mg/l) and an abnormal serum free light chain ratio (< 0.26, or > 1.65)\r\n* Measurable biopsy proven plasmacytoma (should be measured within 28 days of initial investigational agent dosing)Xx_NEWLINE_xXEvaluable MM with at least one of the following: (a) serum monoclonal component ? 0.5 g/dL; or (b) Bence Jones (BJ) proteinuria ? 200 mg/24h; or (c) measurable plasmacytoma (not previously irradiated); or (d) involved serum free light chain ? 10 mg/dL with an abnormal free light chain ratio;Xx_NEWLINE_xXDiagnosis of primary systemic AL amyloidosis of tissue as determined by: a. Congo red staining of tissue showing apple green birefringence AND b. Clonal plasma cell disorder as determined by: i. Immunohistochemistry, in situ hybridization (ISH) or flow cytometry demonstrating kappa or lambda light chain restriction on bone marrow biopsy AND/OR ii. Monoclonal protein on serum or urine electrophoresis/immunofixation OR abnormal free light chain ratioXx_NEWLINE_xXMeasurable disease defined by: a. Monoclonal protein in the serum or urine by immunofixation OR plasmacytosis of bone marrow with monoclonal staining for kappa or lambda light-chain isotype b. dFLC >= 50 mg/L (dFLC=difference in involved and uninvolved serum free light-chain levels)Xx_NEWLINE_xXLight chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratioXx_NEWLINE_xXMeasurable myeloma disease (urine protein > 200 mg in 24 hours [hr] urine collection, serum free light chain ratio > 100 with an abnormal k/l ratio, serum M protein > 0.5 g/dl)Xx_NEWLINE_xXMeasurable disease, as indicated by one of the following:\r\n* Serum monoclonal (M)-protein >= 1.0 g/dL\r\n* Elevated free light chain as per IMWG criteria, and abnormal ratio\r\n* Urine Bence Jones protein > 200 mg/24 hrXx_NEWLINE_xXMeasurable hematologic disease as defined by:\r\n* Serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and non-amyloid forming [uninvolved] free light chain [FLC]) >= 50 mg/L)Xx_NEWLINE_xXMeasurable disease, characterized by one of the following parameters:\r\n* Serum monoclonal (M) protein >= 1 g/dl by protein electrophoresis\r\n* > 200 mg of M protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXPatients with measurable disease defined as at least one of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL by protein electrophoresis\r\n* >= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXPatients must have measurable disease, as defined by at least one of the following:\r\n* Serum monoclonal protein level >= 0.5 g/dL for IgG, IgA, or IgM disease\r\n* Monoclonal protein or total serum IgD >= 0.5 g/dL for IgD disease\r\n* Urinary M-protein excretion of >= 200 mg over a 24-hour period\r\n* Involved free light chain level >= 10 mg/dL, along with an abnormal free light chain ratioXx_NEWLINE_xXPatients must have disease that has relapsed after carfilzomib therapy, with progressive disease (PD) being defined as an increase of 25% from the lowest response value in any one or more of the following:\r\n* Serum M-component (the absolute increase must be >= 0.5 g/dL) and/or\r\n* Urine M-component (the absolute increase must be >= 200 mg/24 hours) and/or\r\n* Only in patients without a measurable serum and urine M protein level: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase) must be > 10 mg/dL\r\n* Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas\r\n* Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder\r\nPatients with relapsed disease will be considered to be those who have had progression, as defined above, off of any therapy, and who completed their therapy more than 60 days prior to the finding of progression; patients with relapsed and refractory disease will be considered to be those who have had progression, as defined above, while still on their last line of therapy, or who progressed within 60 days of finishing their most recent therapyXx_NEWLINE_xXSerum M-protein ?1 g/dL (?10 g/L), ORXx_NEWLINE_xXSerum M-protein ? 0.5 g/dL ORXx_NEWLINE_xXSerum free light chain (FLC) > 100 mg/L of involved FLCXx_NEWLINE_xXParticipants must have a confirmed diagnosis of multiple myeloma as defined by the following criteria:\r\n* Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma\r\n* Monoclonal protein present in the serum and/or urine\r\n* Measurable disease as defined by the following:\r\n** Immunoglobulin G (IgG) multiple myeloma: Serum monoclonal paraprotein (M-protein) level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours\r\n** Immunoglobulin A (IgA) multiple myeloma: Serum M-protein level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours\r\n** Immunoglobulin D (IgD) multiple myeloma: Serum M-protein level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours\r\n** Light chain multiple myeloma: Serum immunoglobulin free light chain >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratioXx_NEWLINE_xXParticipants must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains; measurable disease is defined as one or more of the following: serum M-protein >= 0.5 g/dL, urine M-protein >= 200 mg/24 hour (h), and/or serum free light chain (FLC) assay: involved FLC level >= 10 mg/dL with abnormal serum FLC ratioXx_NEWLINE_xXNonsecretory multiple myeloma based upon standard M-component criteria (i.e., measurable serum/urine M-component) unless the baseline serum free light chain level is elevated; patients with plasmacytomas with biopsy proven known mutations may be included as long as they have evaluable disease by imagingXx_NEWLINE_xXM spike >= 0.5 g/dL or involved free light chain >= 10 mg/dL with an abnormal free light chain ratioXx_NEWLINE_xXMeasurable disease of amyloid light-chain (AL) amyloidosis as defined by at least one of the following:Xx_NEWLINE_xXserum monoclonal (M)-protein greater than or equal (>=) 0.5 grams/deciliter (g/dL) by protein electrophoresis (routine serum protein electrophoresis and immunofixation [IFE] performed at a central laboratory)Xx_NEWLINE_xXserum free light chain greater than or equal to (>=) 5.0 milligram/deciliter (mg/dL) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) >= 5 mg/ dLXx_NEWLINE_xXFOR MULTIPLE MYELOMA ONLY: Measurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL by protein electrophoresis\r\n* >= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXMeasurable disease =< 28 days prior to registration, defined by at least one of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* > 200 mg of monoclonal protein in the urine on 24-hour electrophoresis\r\n* Serum immunoglobulin free light chain > 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio\r\n* Monoclonal bone marrow plasmacytosis > 30% (evaluable disease)Xx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL \r\n* >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXMeasurable disease, prior to initial treatment as indicated by one or more of the following:\r\n* Serum M-protein >= 1 g/dL \r\n* Urine M-protein >= 200 mg/24 hours\r\n* If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable (>= 1 g/dL)\r\n* Involved serum free light chains >= 10 mg/dL provided that free light chain ratio is abnormalXx_NEWLINE_xXNon-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as < 1.0 g/dL M-protein in serum, < 200 mg/24 hr urine M-protein, and no measurable disease as per IMWG by FreeliteXx_NEWLINE_xXHigh risk smoldering multiple myeloma (SMM), defined as follows by Mayo Clinic criteria:\r\n* Bone marrow plasma cells between 10% and 60%\r\n* Serum M-protein >= 3 g/dL (except IgA >= 2 g/dL) or urine M-protein > 500 mg per 24 hours\r\n* Serum free light chain ratio < 0.126 or > 8; an involved to uninvolved ratio of >= 100 is permitted\r\n* Measurable disease, defined as: M-protein >= 1 g/dL OR Bence-Jones protein (BJP) > 200 mg/24 hours (hr) OR involved free light chain > 100 mg/dLXx_NEWLINE_xXFor subjects with MM, measurable disease with serum monoclonal immunoglobulin protein (M-protein) ?1 g/dL, or urine M-protein protein ?200 mg/24 hours, or involved serum free light chain (SFLC) ?10 mg/dL.Xx_NEWLINE_xXPresence of a plasma cell clone (any of the following):\r\n* Monoclonal protein in the serum or urine\r\n* Measurable light chains by free light chain assay\r\n* Measurable plasmacytoma\r\n* Monoclonal plasma cells in bone marrowXx_NEWLINE_xXSubjects must have measurable disease by standard serum and urine tests to enable post-transplant monitoring for progression-free survival; any of the following criteria are sufficient to define measurable disease:\r\n* Serum monoclonal protein spike (M-spike) >= 0.5 g/dL\r\n* 24 hour urine M-spike >= 200mg\r\n* Involved serum free light chain (FLC) >= 50 mg/L with abnormal ratio\r\n* For immunoglobulin A (IgA) multiple myeloma, total serum IgA level elevated above normal range\r\nNote: Measurable disease does not need to be documented at enrollment but can be based on historical lab results obtained at or since diagnosis with multiple myeloma; for example, a patient who does not have measurable disease at enrollment due to complete remission after induction therapy is eligible if the disease was previously measurable by one of the above criteriaXx_NEWLINE_xXHave measurable disease as defined by at least one of the following:\r\n* Serum monoclonal (M) protein >= 0.5 g/dL by protein electrophoresis\r\n* > 200 mg of M protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio\r\n* Monoclonal bone marrow plasmacytosis >= 30%Xx_NEWLINE_xXPatients who have purely non-secretory multiple myeloma (i.e., the absence of a measurable protein in serum by electrophoresis and immunofixation and the absence of Bence-Jones protein in the urine defined by use of electrophoresis and immunofixation)Xx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXSubjects must have relapsed and/or refractory myeloma with measurable disease, as defined by at least one of the following: \r\n* Serum myeloma (M)-protein level >= 0.5 g/dL for immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin M (IgM) disease\r\n* M-protein or total serum immunoglobulin D (IgD) >= 0.5 g/dL for IgD disease\r\n* Urinary myeloma (M)-protein excretion of >= 200 mg over a 24-hour period\r\n* Involved free light chain level >= 10 mg/dL, along with an abnormal free light chain ratioXx_NEWLINE_xXSubjects must have disease that has relapsed and/or refractory after their most recent therapy, with progressive disease (PD) being defined as an increase of 25% from the lowest response value in any one or more of the following: \r\n* Serum M-protein (the absolute increase must be >= 0.5 g/dL) and/or\r\n* Urine M-protein (the absolute increase must be >= 200 mg/24 hours) and/or\r\n* Only in subjects without a measurable serum and urine M protein level: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase) must be > 10 mg/dL\r\n* Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas\r\n* Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorderXx_NEWLINE_xXSubjects must have measurable disease on study entry, which must include at least 1 of the following:\r\n* Serum M-spike >= 0.5 g/dL\r\n* 24 hr urine M-spike >= 200 mg\r\n* Involved serum free light chain (FLC) >= 50 mg/L with abnormal ratio\r\n* Measurable plasmacytoma on exam or imaging\r\n* Bone marrow plasma cells >= 20% (bone marrow biopsy only required at screening if no other measurable disease is present)\r\n** Note: patients with immunoglobulin (Ig)A myeloma in whom serum protein electrophoresis is deemed unreliable, due to co-migration of normal serum proteins with the paraprotein in the beta region, may be considered eligible as long as total serum IgA level is elevated above normal rangeXx_NEWLINE_xXHave a confirmed diagnosis of MM with measurable disease, as defined by the presence of monoclonal immunoglobulin protein in serum electrophoreses of at least 0.5 g/dL for immunoglobulin G (IgG) or 0.25 g/dL for IgA, or measurable light chain in serum (100 mg/L) or urinary excretion of at least 200 mg monoclonal light chain per 24 hoursXx_NEWLINE_xXPatients much have measurable disease, defined as one of the following within 21 days prior to registration:\r\n* Serum M-protein >= 0.5 g/dL\r\n* Urine M-protein >= 200 mg/24 hour (hr)\r\n* Serum free light chain >= 10 mg/dL provided the free light chain (FLC) ratio is abnormal\r\n* 10% plasma cells in bone marrowXx_NEWLINE_xXSerum immunoglobulin free light chains ? 10 mg/dL and abnormal serum immunoglobulin kappa/lambda free light chain ratio), orXx_NEWLINE_xXMeasurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL \r\n* >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain (involved free light chain [FLC]) >=10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio\r\n** NOTE: For patients with no relapse prior to transplant, measurable disease at the time of diagnosis\r\n** NOTE: For patients who have had a disease relapse prior to transplant, measurable disease at the time of the most recent relapse immediately prior to transplant; NOTE: if the patient had treatment for the relapsed disease prior to transplant, the patient must have measurable disease at the time of relapse prior to this therapyXx_NEWLINE_xXPatients must have histologically or cytologically confirmed symptomatic multiple myeloma (MM), Salmon-Durie stage II or III, or International Staging System II or III or fulfill the calcium, renal failure, anemia, and bone lesions (CRAB) criteria; patients should not have previously been treated; finally, patients must meet at least one of the following parameters of measurable disease:\r\n* Bone marrow plasmacytosis with > 10% plasma cells, or sheets of plasma cells, or biopsy proven plasmacytoma which must be obtained within 6 weeks prior to registration\r\n* Measurable levels of M-protein: >= 1 g/dL on serum protein electrophoresis (SPEP) or >= 200 mg of monoclonal light chain on a 24 hour urine protein electrophoresis (UPEP) or involved free light chain (FLC) >= 10 mg/dL (>= 100 mg/L) which must be obtained within 4 weeks prior to registration\r\nSerum and urine M-protein levels should be determined by electrophoresis rather than by quantitative immunoglobulin (Ig) measurement; exceptions are made in cases in which the M-spike value may be deemed to be unreliable (e.g. co-migrating M-spike); in these cases, quantitative Ig should be used; to assess response and progression, however, SPEP values should only be compared to SPEP values and quantitative Ig values only to quantitative Ig valuesXx_NEWLINE_xXMeasurable disease, as indicated by one or more of the following:\r\n* Serum M protein >= 0.5 g/dL\r\n* Urine Bence Jones protein > 200 mg/24 hr\r\n* Elevated free light chain as per International Myeloma Working Group (IMWG) criteria, and abnormal ratioXx_NEWLINE_xXPatients with measurable disease defined as at least one of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL by protein electrophoresis\r\n* > 200 mg of monoclonal protein in the urine on 24-hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXserum M-protein ?1 gm/dL (?10 gm/L).Xx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXSerum M-protein ?1 g/dL (?0.5 g/dL in case of immunoglobulin A [IgA] disease), AND/ORXx_NEWLINE_xXIn the absence of measurable M-protein, serum immunoglobulin free light chain ?10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio (<0.26 or >1.65).Xx_NEWLINE_xXParticipants with light chain and free light chain (FLC) only may be enrolled if they meet all the criteria for a diagnosis of MM.Xx_NEWLINE_xXin subjects without measurable serum or urine M- protein, serum free light chain (SFLC) ? 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratioXx_NEWLINE_xXSubject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI.Xx_NEWLINE_xXSubject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning).Xx_NEWLINE_xXMeasurable disease by IMWG as defined by at least one of the following:\r\n* Serum M-protein >= 0.5 g/dL\r\n* Urine M-protein >= 200 mg in a 24-hour collection\r\n* Serum free light chain level >= 10 mg/dL provided the free light chain ratio is abnormal\r\n* Measurable plasmacytoma; if plasmacytoma measurement is the only measurable disease, subject eligibility must be reviewed with lead principal investigator (PI) prior to signing consentXx_NEWLINE_xXPresence of serum and/or urinary monoclonal proteinXx_NEWLINE_xXSerum M-protein ? 1 g/dLXx_NEWLINE_xXOne or more tumors measurable on radiograph or CT scan, or evaluable disease defined as non-measurable lesions per RECIST or detection of protein M in serum and/or urine of patients with Multiple Myeloma (serum ? 10 gm/L and urine ? 200 mg/24 hr).Xx_NEWLINE_xXMeasurable disease defined by serum M-protein ?1 g/dL, or urine light chain ?200 mg/24 hours, or abnormal serum FLC ratio with involved FLC > 10 mg/dL provided serum FLC ratio is abnormalXx_NEWLINE_xXThe subject has measurable disease with at least one of the following: Serum M-protein >=0.5 gram per deciliter (g/dL) (>=5 gram per Liter [g/L]); Urine M-protein >=200 milligram per 24 hours (mg/24h); Serum Free light chain (FLC) assay: Involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65).Xx_NEWLINE_xXMust have at least ONE aspect of measurable disease, defined as one the following: Urine M-protein excretion >=200 milligram (mg)/24 hours, or; Serum M-protein concentration >=0.5 gram (g)/deciliter (dL) (>=5.0 g/Liter), or; Serum free light chain (FLC) assay: involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).Xx_NEWLINE_xXPatients with non-secretory multiple myeloma (absence of a monoclonal protein [M protein] in serum as measured by electrophoresis [serum protein electrophoresis (SPEP)] and immunofixation (serum immunofixation electrophoresis [SIFE]) and the absence of Bence Jones protein in the urine [urine protein electrophoresis (UPEP)] defined by use of conventional electrophoresis and immunofixation [urine immunofixation electrophoresis (UIFE) techniques]) but with measurable disease on imaging studies like magnetic resonance imaging (MRI), computed tomography (CT) scan or positron emission tomography (PET) scan.Xx_NEWLINE_xXMeasurable disease defined as at least one of the following: serum M-protein >/=1 grams/deciliter (g/dL), urine M-protein >/= 200 milligrams/24 hours (mg/24h), serum free light chain (SFLC) assay: involved SFLCs >/= 10 mg/dL (>/= 100 mg/L) and an abnormal SFLC ratio (<0.26 or >1.65).Xx_NEWLINE_xXSubjects must have documented multiple myeloma as defined by the criteria below:\r\n* Clonal bone marrow plasma cells >= 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following calcium, renal failure, anemia, bone lesions (CRAB) features and myeloma-defining events (MDEs)\r\n* Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:\r\n** Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL)\r\n** Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177 umol/L (> 2 mg/dL)\r\n** Anemia: hemoglobin value of > 20 g/L below the lowest limit of normal, or a hemoglobin value < 100 g/L\r\n** Bone lesions: one or more osteolytic lesion on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)/CT\r\n* Any one or more of the following biomarkers of malignancy (MDEs)\r\n** 60% or greater clonal plasma cells on bone marrow examination\r\n** Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved free light chain is at least 100 mg/L (a patient’s “involved” free light chain – either kappa or lambda – is the one that is above the normal reference range; the uninvolved light chain is the one that typically is in, or below, the normal range)\r\n** More than one focal lesion on magnetic resonance imaging (MRI) that is at least 5 mm or greater in sizeXx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least one of the following:\r\n* Serum monoclonal protein >= 0.5 g/dL\r\n* >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum free light chain >= 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free kappa light chain ratioXx_NEWLINE_xXSubjects must have measurable disease, as defined by at least one of the following:\r\n* Serum monoclonal protein M-protein level >= 0.5 g/dL \r\n* Urinary M-protein excretion of >= 200 mg over a 24-hour period\r\n* Involved free light chain level >= 10 mg/dL, along with an abnormal free light chain ratioXx_NEWLINE_xXSubjects must have disease that has relapsed and/or refractory after their most recent therapy, with progressive disease (PD) being defined as an increase of 25% from the lowest response value in any one or more of the following:\r\n* Serum M-component protein (the absolute increase must be >= 0.5 g/dL) and/or\r\n* Urine M-component protein (the absolute increase must be >= 200 mg/24 hours) and/or\r\n* Only in subjects without a measurable serum and urine M protein level: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase) must be > 10 mg/dL\r\n* Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas\r\n* Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorderXx_NEWLINE_xXSerum monoclonal protein ? 0.5 g/dLXx_NEWLINE_xXSerum immunoglobulin free light chain >10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)Xx_NEWLINE_xXSerum M protein ? 0.5 /dL (? 5 g/L)Xx_NEWLINE_xXSerum free light chain (FLC) assay: involved FLC assay ? 10 mg/dL (? 100 mg/L) and an abnormal serum FLC ratio (< 0.26 or > 1.65)Xx_NEWLINE_xXPatients with measurable disease as defined by any of the following:\r\n* Serum M-protein >= 0.5 g/dl (>= 500 mg/dL)\r\n* Urine monoclonal protein >= 200 mg/24h\r\n* Involved free light chain (FLC) level >= 10 mg/dl (>= 100 mg/l) and an abnormal serum free light chain ratio (< 0.26, or > 1.65)Xx_NEWLINE_xXHigh risk disease defined by all of the following:\r\n* >= 10% bone marrow plasma cells AND\r\n* Abnormal serum free light chain (FLC) ratio (< 0.26 or > 1.65) by serum FLC assay AND\r\n* Monotypic plasma cell S-phase >= 0.3%Xx_NEWLINE_xXPatient is at higher than average risk of progression to active MM, defined as having 2 or more of the following features:\r\n* Serum M-protein >= 3 g/dL\r\n* BMPC > 10% and < 60%\r\n* Abnormal serum free light chains (FLC) ratio (0.26-1.65)Xx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis \r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXPatients with MM must have measurable disease, defined as one or more of the following:\r\n* Serum M-protein >= 0.5 g/dL\r\n* Urine M-protein >= 200 mg/24 hr\r\n* Serum immunoglobulin free light chain (FLC) >= 100 mg/L (10 mg/dL) and abnormal serum immunoglobulin kappa to lambda FLC ratio\r\n** IgA patients must have serum quantitative immunoglobulin >= 750 mg/dL\r\n** Patients with oligosecretory or non-secretory disease must have a documented abnormal free light chain ratio (normal value 0.26 to 1.65) or a value beyond the laboratory calculation rangeXx_NEWLINE_xXSystemic amyloid light chain amyloidosisXx_NEWLINE_xXHad measurable disease of MM at diagnosis, defined as:\r\n* A monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or\r\n* Urine monoclonal protein levels of at least 200 mg/24 hours\r\n* For subjects without measurable serum or urine M-protein levels, an abnormal free light chain ratio (normal value: 0.26-1.65) with involved free light chain (FLC) level >= 10 mg/dL (>= 100 mg/L)\r\n* “Measurable disease” is NOT required at the time of enrollment; final determination of measurable disease requirement is at principal investigator's (PI’s) discretionXx_NEWLINE_xXPatients must have measurable MM as defined by at least one of the criteria below\r\n* One or more of these abnormalities defines measurable disease:\r\n* Serum M-protein greater or equal to 0.4 g/dl (10 g/l)\r\n* Urine M-protein greater or equal to 200 mg/24 hour (h)\r\n* Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dl (100 mg/l) provided serum FLC ratio is abnormal\r\n* A biopsy-proven plasmacytomaXx_NEWLINE_xXMust have measurable disease defined as any of the following: serum m-spike >= 1 g/dL, 24 hour (h) urine m-spike of at least 200 mg/d, involved serum free light chains >= 100 mg/L with abnormal serum free light chain ratio, bone marrow plasma cells of at least 30%Xx_NEWLINE_xXPatients must have measurable disease as defined as at least one of the following (these baseline laboratory studies for determining eligibility must be obtained within 28 days prior to enrollment):\r\n* Serum M-protein >= 0.5 g/dl (>= 5 g/l)\r\n* Urine M-protein >= 200 mg/24 h\r\n* Serum free light chains (FLC) assay: involved FLC level >= 10 mg/dl (>= 100 mg/l) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)\r\n* Biopsy proven plasmacytoma (should be measured within 28 days of first study drug administration); prior biopsy is acceptable\r\n* If the serum protein electrophoresis is unreliable for routine M-protein measurement, quantitative immunoglobulin levels on nephelometry or turbidimetry will be followedXx_NEWLINE_xXPatients must have serum protein electrophoresis (SPEP) and kappa and lambda light chain testing performed within 14 days prior to registration in order to establish baseline measurementsXx_NEWLINE_xXCriteria for cohort A (recently diagnosed subjects to receive AHCT)\r\n* Must have presence of clonal plasma cells in the bone marrow greater or equal to 10% or biopsy proven plasmacytoma\r\n* Must have either (a) presence of myeloma protein (M-component) (immunoglobulin [Ig]G or IgA) in serum greater or equal to 1 g/dl or in urine greater or equal to 200 mg/24 hours (h); or (b) presence of an abnormal serum free light chain (FLC) ratio on the serum FLC assayXx_NEWLINE_xXCriteria for cohort B (multiply relapsed multiple myeloma)\r\n* Must have measurable MM, as defined by: serum myeloma protein (M-protein) >= 1 g/dL, urine M-protein >= 200 mg/24 hours, involved serum free light chain (FLC) level >= 10 mg/dL, biopsy proven plasmacytoma, or more than 30% bone marrow plasma cells\r\n* Must have received at least 2 different treatment regimens for MMXx_NEWLINE_xXParticipants must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains; measurable disease is defined as one or more of the following: serum M-protein >= 1 g/dl (except patients with immunoglobulin [Ig] D or IgA myeloma), urine M-protein >= 200 mg/24 hour (h), and/or serum free light chain (FLC) assay: involved FLC level >= 10 mg/dl with abnormal serum FLC ratio; for patients with IgD or IgA myeloma, a serum M-protein of greater than or equal to 0.5 g/dl will suffice; free light chain patients not measurable by urine or serum evaluation may be considered for inclusionXx_NEWLINE_xXInclusion Criteria:\n\n        Measurable MM based on modified IMWG guidelines. Defined by at least one of the following:\n\n          1. Serum M-protein ? 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by\n             quantitative IgA\n\n          2. Urinary M-protein excretion ? 200 mg/24 hours\n\n          3. Free Light Chain (FLC) ? 100 mg/L, provided that the FLC ratio is abnormal\n\n          4. If serum protein electrophoresis is felt to be unreliable for routine M-protein\n             measurement, then quantitative Ig levels by nephelometry or turbidimetry are\n             acceptable\n\n               -  Must have previously received ? 3 anti-MM regimens including: an alkylating\n                  agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a\n                  glucocorticoid. There is no upper limit on the number of prior therapies provided\n                  that all other inclusion/exclusion criteria are met.\n\n               -  MM refractory to previous treatment with one or more glucocorticoids, parenteral\n                  PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or\n                  pomalidomide), and the anti-CD38 mAb, daratumumab. Refractory is defined as ? 25%\n                  response to therapy, or progression during therapy or progression within 60 days\n                  after completion of therapy.\n\n        Exclusion Criteria:\n\n          -  Active smoldering MM.\n\n          -  Active plasma cell leukemia.\n\n          -  Documented systemic amyloid light chain amyloidosis.\n\n          -  Active CNS MM.Xx_NEWLINE_xXPatients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 60 months, as confirmed by both of the following:\r\n* Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells at any time before initiating study treatment, including a marrow which must be obtained by bone marrow aspiration and/or biopsy within 4 weeks prior to randomization\r\n* Abnormal serum free light chain ratio (< 0.26 or > 1.65) by serum free light chain (FLC) assay; FLC assay must be performed within 28 days of randomizationXx_NEWLINE_xXSubjects must have measurable disease including at least one of the criteria below: Serum M-protein greater or equal to 0.5 g/dL Urine M-protein greater or equal to 200 mg/24 h Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal -Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study Part A: Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), or have \double refractory\ disease to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agentsXx_NEWLINE_xXPatients diagnosed with symptomatic multiple myeloma based on International Myeloma Working Group (IMWG) diagnostic criteria; according to these criteria, patient must have monoclonal plasma cells in the bone marrow >= 10% and/or presence of a biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events:\r\n* Clonal bone marrow plasma cell percentage >= 60% (Note: clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence; bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate, the highest value should be used) \r\n* Involved: uninvolved serum free light chain ratio >= 100 (values are based on the serum Freelite assay); the involved free light chain must be >= 10 mg/dL\r\n* > 1 focal lesions on magnetic resonance imaging (MRI) studies (each focal lesion must be 5 mm or more in size) \r\n* (C) Calcium elevation in the blood, defined as serum calcium > 11 mg/dL or > 1 mg/dL higher than the upper limit of normal\r\n* (R) Renal insufficiency, defined as serum creatinine > 2 mg/dl or creatinine clearance < 40 mL/min\r\n* (A) Anemia, defined as hemoglobin < 10 g/dl or > 2 g/dl below the lower limit of normal\r\n* (B) Lytic bone lesions, one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT (if bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement)Xx_NEWLINE_xXPatients with measurable disease defined as one or more of the following: serum M-protein >= 1.0 g/dl, urine M-protein >= 200 mg/24 hour (h), and/or serum free light chain (FLC) assay: involved FLC level >= 10 mg/dl with abnormal serum FLC ratioXx_NEWLINE_xXParticipant must have documented multiple myeloma satisfying the CRAB (calcium elevation, renal insufficiency, anemia and bone abnormalities) criteria, monoclonal plasma cells in the bone marrow greater than or equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma and measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >=1.0 gram/deciliter [g/dL] or urine M-protein level >=200 milligram[mg]/24 hours[hrs]; or (b) IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level >=0.5 g/dL or urine M-protein level >=200 mg/24 hrs); or (c) light chain multiple myeloma without measurable disease in serum or urine (serum immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)Xx_NEWLINE_xXMeasurable disease, as defined by at least one of the following: Serum M protein 0.5 g/dL or higher, Urine M protein 200 mg/24 hr or higher, Serum free light chain (SFLC) 10 mg/dL or higher, and Abnormal SFLC ratio.Xx_NEWLINE_xXMust have measurable disease as defined by m-protein or serum free light chain.Xx_NEWLINE_xXMeasurable disease as defined by serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and nonamyloid forming [uninvolved] free light chain [FLC]) ? 50 mg/L.Xx_NEWLINE_xXSerum monoclonal protein (SPEP) ?1 g/dLXx_NEWLINE_xXSerum free light chain (SFLC): involved FLC ?10 mg/dL (?100 mg/L) AND abnormal kappa to lambda serum free light chain ratioXx_NEWLINE_xXAbnormal serum free light-chain ratio ?100 (involved kappa) or < 0.01 (involved lambda)Xx_NEWLINE_xXLight chain MM: Serum M-protein level ? 1.0 g/dl or urine M-protein level ? 200 mg/24 hours 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 6. Females of childbearing potential (FCBP1) must:Xx_NEWLINE_xXSerum M protein ?0.5 g/dL (?5 g/L);Xx_NEWLINE_xXSerum free light chain (FLC) assay: Involved FLC assay ?10 mg/dL (?100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).Xx_NEWLINE_xXSerum monoclonal protein (SPEP) ?1 g/dL.Xx_NEWLINE_xXNonsecretory myeloma or free light chain detected in serum only (ogliosecretory).Xx_NEWLINE_xXSerum monoclonal protein ? 0.5 g/dL by protein electrophoresisXx_NEWLINE_xXSerum immunoglobulin free light chain ?10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXFree Light Chain measurable disease only.Xx_NEWLINE_xXParticipant has measurable disease at Screening, defined as at least one of the following: Serum M-protein greater than or equal to 0.5 g/dL, OR Urine M-protein greater than or equal to 200 mg in 24-hours, OR serum immunoglobulin free light chain (FLC) greater than or equal to 10 mg/dL provided serum FLC ratio is abnormal.Xx_NEWLINE_xXMeasurable disease as defined by any of the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >=1.0 gram/deciliter [g/dL] or urine M-protein level greater than or equal to (>=) 200 milligram[mg]/24 hours[hrs]; or (b) IgA, IgD, or IgE multiple myeloma (serum M-protein level >= 0.5 g/dL or urine M-protein level >= 200 mg/24 hrs); or (c) light chain multiple myeloma (serum immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)Xx_NEWLINE_xXMeasureable disease by Serum M protein, or Urine M protein, or serum free light chain (SFLC) and an abnormal serum kappa lambda ratio (for subjects without detectable serum or urine M-protein), or Serum quantitative immunoglobulin A (qlgA) (for immunoglobulin (Ig) A subjects whose disease can only be reliable measured by qlgA).Xx_NEWLINE_xXPrimary systemic AL (immunoglobulin light chain) amyloidosisXx_NEWLINE_xXPatients with multiple myeloma in complete remission (CR), partial remission (PR), or very good partial remission (VGPR), or symptomatic stable disease (no evidence of progression) including patients with light chain MM detected in the serum by free light chain assayXx_NEWLINE_xXPatients with non-secretory multiple myeloma (absence of a monoclonal protein [M protein] in serum as measured by electrophoresis [serum protein electrophoresis (SPEP)] and immunofixation [serum immunofixation electrophoresis (SIFE)] and the absence of Bence Jones protein in the urine [urine protein electrophoresis (UPEP)] defined by use of conventional electrophoresis and immunofixation [urine immunofixation electrophoresis (UIFE)] techniques) but with measurable disease on imaging studies like magnetic resonance imaging (MRI), computed tomography (CT) scan or positron emission tomography (PET) scanXx_NEWLINE_xXMust meet criteria of high risk smoldering MM based on the criteria described below:\r\n* Definition of high-risk smoldering multiple myeloma (SMM):\r\n** Bone marrow clonal plasma cells >= 10% and =< 60% and any one or more of the following:\r\n*** Serum monoclonal (M) protein >= 3.0 g/dL (IgA, IgG, IgM, or IgD)\r\n*** IgA SMM\r\n*** Immunoparesis with reduction of two uninvolved immunoglobulin isotypes\r\n*** Serum involved/uninvolved free light chain ratio >= 8 (but less than 100)\r\n**** Free light chain smoldering myeloma patients are not excluded\r\n*** Progressive increase in M protein level (evolving type of SMM)\r\n**** Increase in serum monoclonal protein by >= 10% on two successive evaluations within a 6 month period\r\n*** Bone marrow clonal plasma cells 50-60%\r\n*** Abnormal plasma cell immunophenotype (>= 95% of bone marrow plasma cells are clonal) and reduction of one or more uninvolved immunoglobulin isotypes\r\n*** t (4;14) or del 17p or 1q gain\r\n*** Increased circulating plasma cells\r\n*** Magnetic resonance imaging (MRI) with diffuse abnormalities or 1 focal lesion\r\n*** Positron emission tomography (PET)-computed tomography (CT) with one focal lesion with increased uptake without underlying osteolytic bone destruction\r\n*** Urine monoclonal light chain excretion >= 500 mg/24 hoursXx_NEWLINE_xXNo evidence of increased calcium levels, renal insufficiency, anemia or bone lesions (CRAB criteria) or new criteria of active MM which including the following:\r\n* Increased calcium levels (corrected serum calcium > 0.25 mmol/dL [> 1mg/dL] above the upper limit of normal or > 2.75 mmol/dL [11mg/dL]) related to MM\r\n* Renal insufficiency (attributable to MM)\r\n** Participants with creatinine levels =< 1.5 mg/dL not attributable to myeloma are eligible\r\n* Anemia (hemoglobin [Hb] 2 g/dL below the lower limit of normal or < 10 g/dL) related to MM\r\n* Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)\r\n* Bone marrow plasma cells >= 60%\r\n* Serum involved/uninvolved free light chain (FLC) ratio >= 100, provided the absolute level of the involved free light chain is at least 100 mg/L and repeated twice (light chain smoldering myeloma is not an exclusion criteria)\r\n* MRI with two or more focal lesions that are at least 5 mm or greater in size\r\n* Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligibleXx_NEWLINE_xXSerum myeloma protein (M-protein) >= 3 g/dl and/or bone marrow plasma cells >= 10 %Xx_NEWLINE_xXAbsence of involved: uninvolved serum free light chain ratio >= 100Xx_NEWLINE_xXWithin the past 4 weeks: Serum monoclonal protein >= 1.0 g/dlXx_NEWLINE_xXWithin the past 4 weeks: Serum immunoglobulin free light chain > 10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)Xx_NEWLINE_xXOne or more of the following biomarkers of malignancy:\r\n* Clonal bone marrow plasma cell percentage >= 60%\r\n* Involved: uninvolved serum free light chain ratio >= 100\r\n* > 1 focal lesions on magnetic resonance imaging (MRI) studiesXx_NEWLINE_xXParticipants must also have measurable disease according to the Standard Diagnostic Criteria:\r\n* Serum immunoglobulin (Ig)G, IgA, or IgM M-protein >= 0.5 g/dL, or\r\n* Serum IgD M-protein >= 0.05 g/dL, or\r\n* Urinary M-protein excretion of more than 200 mg/24 hours, or\r\n* Serum free light chains of at least 100 mg/L with an abnormal free light chains (FLC) ratioXx_NEWLINE_xXSerum M-protein ? 0.5 g/dLXx_NEWLINE_xXIn subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratioXx_NEWLINE_xXParticipants must also have measurable disease according to the Standard Diagnostic Criteria:\r\n* Serum immunoglobulin (Ig)G, IgA, or IgM M-protein >= 0.5 g/dL, or\r\n* Serum IgD M-protein >= 0.05 g/dL, or\r\n* Urinary M-protein excretion of more than 200 mg/24 hours, or\r\n* Serum free light chains of at least 100 mg/dL with an abnormal free light chain (FLC) ratioXx_NEWLINE_xXMeasurable disease as defined by one or more of the following criteria (assessed within 28 days prior to registration):\r\n* Serum paraprotein >= 5 g/L (for immunoglobulin A [IgA] patients whose disease can only be reliably measured by serum quantitative immunoglobulin [IgA]: >= 7.5 g/L)\r\n* Urine Bence Jones protein: >= 200 mg/24 hours (h) \r\n* Serum light chain assay: Involved free light chain (FLC) level >= 100 mg/L, provided serum FLC ratio is abnormalXx_NEWLINE_xXMeasurable serum paraprotein on serum protein electrophoresis (SPEP) or serum free light chains and ratio, or quantifiable Bence-Jones proteinuria on 24 hour urine specimen; if the monoclonal protein has merged with the beta region will follow the serum immunoglobulin of the involved heavy chain and comment on either partial remission (PR, as judged by two protocol investigators) or complete remission (CR, as defined by the achievement of PR as above and the resolution of the monoclonal protein by immunofixation in the serum and urine)Xx_NEWLINE_xXPatients must have measurable myeloma paraprotein levels in serum (>= 0.5 g/dL) or urine (>= 0.2 g excreted in a 24-hour urine collection sample) or by free light chain (involved free light chain greater than 100 mg/L)Xx_NEWLINE_xXPatients must currently have measurable disease, as defined as:\r\n* Serum M protein >= 0.5 g/dl\r\n* Urine M protein >= 200 mg/24h\r\n* Serum free light chain assay: involved free light chain (FLC) level >= 10 mg/dl (>= 100 mg/l) provided serum FLC ratio is abnormal\r\n* If no monoclonal protein is detected (non-secretory disease), then > 30% monoclonal bone marrow plasma cellsXx_NEWLINE_xXPatients must have measurable disease defined as one of the following:\r\n* Serum M protein >= 0.5 g/dL\r\n* Urine M protein >= 200 mg/24 hours\r\n* Serum free light chain >= 10 mg/dL provided the free light chain (FLC) ratio is abnormalXx_NEWLINE_xXMeasurable disease, as defined by one or all of the following (assessed within 30 days prior to initiation of therapy): a) serum M-protein >= 0.5 g/d; b) urine Bence-Jones protein >= 200 mg/24 hours; c) patients with light chain only myeloma are eligible; the involved free light chain level 100 mg/L with abnormal serum free light chain ratioXx_NEWLINE_xXPatients with evidence of relapse or refractory disease as defined by International Myeloma Working Group (IMWG) criteria and measurable disease as defined by any of the following:\r\n* Serum M-protein >= 0.5 g/dl (>= 10 g/l)\r\n* Urine monoclonal protein >= 200 mg/24 h\r\n* Involved free light chain (FLC) level >= 10 mg/dl (>= 100 mg/l) and an abnormal serum free light chain ratio (< 0.26, or > 1.65)\r\n* Measurable biopsy proven plasmacytoma (should be measured within 28 days of registration to study)Xx_NEWLINE_xXMeasurable MM disease, defined as one of the following:\r\n* A monoclonal immunoglobulin (Ig) concentration on serum electrophoresis of >= 0.5 g/dL for an IgG myeloma, >= 0.1 g/dL for an IgD myeloma or >= 0.5 g/dL for an IgA myeloma\r\n* Measurable urinary light chain secretion by quantitative analysis of >= 200 mg/24 hours\r\n* Involved serum free light chain (FLC) level >= 10 mg/dL, provided the serum FLC ratio is abnormal\r\n* Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosis on aspirationXx_NEWLINE_xXSerum M-protein ? 500 mg/dLXx_NEWLINE_xXFor patients without measurable serum or urine M protein, serum free light chain (SFLC): Involved free light chain (FLC) concentration ? 10 mg/dL provided SFLC ratio is abnormalXx_NEWLINE_xXMust have measurable levels of myeloma paraprotein in serum (? 0.5 g/dL) or urine (? 0.2 g/24 hours)Xx_NEWLINE_xXParticipants must have myeloma that is measurable; measurable disease is defined as one or more of the following:\r\n* Serum M-protein >= 0.5 g/dl,\r\n* Urine M-protein >= 200 mg/24 hour (h), and/or\r\n* Serum free light chain (FLC) assay: involved FLC level >= 10 mg/dl with abnormal serum FLC ratioXx_NEWLINE_xXMeasurable disease as defined by any of the following International Myeloma Working Group Criteria\r\n* Monoclonal serum peak of greater than 0.5 gms per deciliter\r\n* Measurable urine peak as defined by urine protein electrophoresis of greater than 100 mg per 24 hours\r\n* Involved light chain versus uninvolved light chain ratio of greater than 100Xx_NEWLINE_xXPatients must not have measurable disease at the time of enrollment. Measurable disease is defined as follows-\r\n* Serum monoclonal protein > 1 gm/dL\r\n* Urine monoclonal protein > 200 mg/24 hours\r\n* Involved serum free light chain > 10 mg/dLXx_NEWLINE_xXNewly diagnosed patients with histologically confirmed multiple myeloma (MM) based on the following criteria:\r\n* Clonal plasma cells in the bone marrow\r\n* Measurable disease within the past 4 weeks defined by any one of the following:\r\n** Serum monoclonal protein >= 1.0 g/dL\r\n** Urine monoclonal protein > 200 mg/24 hour\r\n** Involved serum immunoglobulin free light chain > 10 mg/dL AND abnormal kappa/lambda ratioXx_NEWLINE_xXEvidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following:\r\n* Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) above upper limit of normal or >= 2.75 mmol/L (11 mg/dL)\r\n* Anemia: hemoglobin value < 10 g/dL or > 2 g/dL below lower limit of normal\r\n* Bone disease: >= 1 lytic lesions on skeletal X-ray, computed tomography (CT), or positron emission tomography (PET)-CT; for patients with 1 lytic lesion, bone marrow should demonstrate >= 10% clonal plasma cells\r\n* Clonal bone marrow plasma cell percentage >= 60%\r\n* Involved/un-involved serum free light chain ratio >= 100 and involved free light chain > 100 mg/L\r\n* > 1 focal lesion on magnetic resonance imaging study (lesion must be > 5 mm) in sizeXx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio\r\n* Monoclonal plasmacytosis >= 30% (evaluable disease)\r\n* Measurable plasmacytoma that has not been radiatedXx_NEWLINE_xXPatients with light chain only myeloma are eligible; the involved free light chain level >= 100 mg/L with abnormal serum free light chain ratioXx_NEWLINE_xXPatients must have measurable disease on study entry. Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein. For patients with minimally secretory disease on study entry, serum free kappa or lambda light chain levels, or the serum free light chain ratio may be measured and used for disease monitoring if abnormal.Xx_NEWLINE_xXProtein criteria must be present at diagnosis (quantifiable M-component of immunoglobulin [Ig]G, IgA, IgD, or IgE and/or urinary kappa or lambda light chain, Bence-Jones protein, or free kappa light chain or free lambda light chain) in order to evaluate response; non-secretory participants are eligible provided the participant has >= 20% plasmacytosis OR multiple (>= 3) plasmacytomas or lesions on magnetic resonance imaging (MRI) at the time of diagnosis or study enrollment, OR the presence of lesions on positron emission tomography (PET)/computed tomography (CT) scan or skeletal survey at diagnosis or study enrollmentXx_NEWLINE_xXMeasurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >=10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio\r\n* Bone marrow plasma cells >= 30%\r\n* NOTE: For patients with no relapse prior to transplant, measurable disease at the time of diagnosis\r\n* NOTE: For patients who have had a disease relapse prior to transplant, measurable disease at the time of the most recent relapse immediately prior to transplant; NOTE: If the patient had treatment for the relapsed disease prior to transplant, the patient must have measurable disease at the time of relapse prior to this therapyXx_NEWLINE_xXMeasurable disease, prior to initial treatment as indicated by one or more of the following:\r\n* Serum monoclonal (M)-protein >= 0.5 g/dL\r\n* Urine M-protein >= 200 mg/24 hours\r\n* If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptableXx_NEWLINE_xXNon-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as < 0.5 g/dL M-protein in serum, < 200 mg/24 hour (hr) urine M-protein, or disease only measured by serum free light chainXx_NEWLINE_xXMeasurable disease at Screening: Serum monoclonal protein greater than or equal to 1 g/dL by protein electrophoresis, or greater than or equal to 200 mg monoclonal protein in the urine on 24-hr electrophoresis, or serum immunoglobulin free light chain greater than or equal to 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio.Xx_NEWLINE_xXMeasurable disease for phase IIa portion only\r\n* Lymphoma (includes cutaneous T-cell lymphoma [CTCL] patients who have no evidence of disease [NED] in skin): computed tomography (CT) or positron emission tomography (PET)/CT by modified Cheson criteria with incorporation of PET\r\n* Multiple myeloma: patient must have measurable disease and therefore must have at least one of the following:\r\n** Serum myeloma protein (M-protein) >= 0.5 gm/dL (>= 5 gm/L)\r\n** Urine M-protein >= 200 mg/24 hours (hr)\r\n** Serum free light chain (FLC) assay: involved FLC >= 10 mg/dL (>= 100 mg/L) provided serum FLC ratio is abnormal\r\n* CTCL: Modified Severity-Weighted Assessment Tool (mSWAT) > 0 or absolute Sezary count >= 1,000 cells/uLXx_NEWLINE_xXPatients must have measurable disease as defined by the International Uniform Response Criteria, defined as any of the following:\r\n* Serum M-protein >= 500 mg/dL\r\n* Urine M-protein of >= 200 mg/24 hours\r\n* Involved free light chain >= 10 mg/dL provided serum free light chain ratio is abnormalXx_NEWLINE_xXMeasurable light chain elevation, as defined by:\r\n* A difference between the involved immunoglobulin free light chain and uninvolved light chain and uninvolved light chain (dFLC) of >= 5 mg/dL AND abnormal serum immunoglobulin kappa lambda free light chain ratio\r\n* EXCEPTION: during the DOSE ESCALATION PORTION of the study only, a measurable M-protein (>= 0.5 g/dL) on serum protein electrophoresis (SPEP) or a measurable urinary light chain (>= 200 mg/24 hrs) by urine protein electrophoresis (UPEP) without a dFLC meeting the above criteria is acceptable; subjects without a dFLC >= 5 mg/dL treated at the MTD will not count towards the expansion cohortXx_NEWLINE_xXSerum M-protein ? 1 g/dL (? 10 g/L).Xx_NEWLINE_xXSerum free light chain (FLC) assay: involved FLC level ? 10 mg/dL (? 100 mg/L), provided that the serum FLC ratio was abnormal.Xx_NEWLINE_xXDiagnosis of high-risk SMM (defined as bone marrow plasma cells >=10% and either serum monoclonal protein >=3 g/dL, or abnormal free light chain ratio <0.126 or >8 and serum M-protein <3 g/dL but >=1 g/dL)Xx_NEWLINE_xXPrimary systemic amyloid light (AL) chain amyloidosis (a build-up of amyloid light chain proteins in the blood)Xx_NEWLINE_xXSerum M-protein ? 0.5 g/dLXx_NEWLINE_xXSerum free light chain (FLC) > 100 mg/L of involved FLCXx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXSerum monoclonal protein >0.5g/dL and/or 0.2g/24hr urine light chain excretionXx_NEWLINE_xXMeasurable MM disease, defined as one of the following: \r\n* A monoclonal immunoglobulin (Ig) concentration on serum electrophoresis of >= 0.5 g/dL for an IgG myeloma, >= 0.1 g/dL for an IgD myeloma or 0.5 g/dL for an IgA myeloma\r\n* Measurable urinary light chain secretion by quantitative analysis of >= 200 mg/24 hours\r\n* Involved serum free light chain (FLC) level >= 10 mg/dL, provided the serum FLC ratio is abnormal\r\n* Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosisXx_NEWLINE_xXRelapsed/refractory MM with failure to at least two lines of MM treatment which must include at least one IMiD (thalidomide, lenalidomide) and proteosome inhibitor (bortezomib) and 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. Oligo or non secretory myeloma patients may be included, if there is measurable plasmacytosis in the bone marrow biopsy or measurable extramedullary disease.Xx_NEWLINE_xXSubjects with non-secretory or oligo-secretory or serum free light-chain only myelomaXx_NEWLINE_xXDemonstrate measurable disease as defined by one or more of the following:\r\n* Serum monoclonal protein >= 0.5 g/dL by serum electrophoresis\r\n* Urine monoclonal protein > 200 mg/dL in a 24 hr urine electrophoresis\r\n* Demonstrate clonal population of plasma cells in the bone marrow or abnormal free light chain (FLC) ratioXx_NEWLINE_xXMust have a detectable serum or urine M-Protein by protein electrophoresis that is at least 500 mg/dL (serum) or 1 gm/24 hours (urine), respectively, or serum free light chain level >100 mg/l for the involved free light chain.Xx_NEWLINE_xXMeasurable 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%Xx_NEWLINE_xXPatients with (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine) unless measurable disease is available with imaging techniques such as MRI and PET scan.Xx_NEWLINE_xXNewly diagnosed patients with histologically confirmed multiple myeloma (MM) based on the following criteria:\r\n* Clonal plasma cells in the bone marrow\r\n* Measurable disease within the past 4 weeks defined by any one of the following:\r\n** Serum monoclonal protein >= 1.0 g/dL\r\n** Urine monoclonal protein > 200 mg/24 hour \r\n** Involved serum immunoglobulin free light chain > 10 mg/dL AND abnormal kappa/lambda ratioXx_NEWLINE_xXEvidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following:\r\n* Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) above upper limit of normal or >= 2.75 mmol/L (11 mg/dL)\r\n* Anemia: hemoglobin value < 10 g/dL or > 2 g/dL below lower limit of normal\r\n* Bone disease: >= 1 lytic lesions on skeletal X-ray, computed tomography (CT) or positron emission tomography (PET)-CT; for patients with 1 lytic lesion, bone marrow should demonstrate >= 10% clonal plasma cells\r\n* Clonal bone marrow plasma cell percentage >= 60%\r\n* Involved/un-involved serum free light chain ratio >= 100 and involved free light chain > 100mg/L\r\n* > 1 focal lesion on magnetic resonance imaging study (lesion must be > 5 mm) in sizeXx_NEWLINE_xXMeasurable multiple myeloma disease, defined as meeting at least 1 of the following criteria within 14 days prior to registration: \r\n* A monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of >= 0.5 g/dL\r\n* Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of >= 200 mg/24 hours\r\n* Involved serum free light chain (FLC) level >= 10 mg/dL, provided the serum FLC ratio is abnormal\r\n* Presence of extramedullary plasmacytomasXx_NEWLINE_xXPatients with measurable disease as defined by a history of an elevated myeloma protein (M component) in plasma, urine, or free kappa/lambda light chains in the serumXx_NEWLINE_xXMonoclonal protein in the serum of >= 0.5 gm/dL or monoclonal light chain in the urine protein electrophoresis of >= 200 mg/ 24 hours, or measurable light chains by free light chain assay of >= 10 mg/dL, or measurable plasmacytomaXx_NEWLINE_xXMyeloma relapsing from partial response or better\r\n* Patients relapsing > 18 months from transplant if not on maintenance, or\r\n* If off maintenance, discontinued at least 6 months ago, or\r\n* If relapsing on maintenance, at least 3 years from transplant, or\r\n* Off prior myeloma therapy at least 6 months ago\r\n* Sufficient tumor burden that is assessable for response\r\n** Serum M-spike >= 0.5 g/dL, or\r\n** If immunoglobulin A (IgA) myeloma, IgA > 1000 mg/dL, or\r\n** Difference between involved and uninvolved free light chain (dFLC) > 10 mg/dL, or\r\n** Urine M-spike >= 200 mg/24 hours, or\r\n** Bone marrow plasmacytosis >= 10%, or\r\n** Plasmacytoma >= 2 cm in diameterXx_NEWLINE_xXKey Inclusion Criteria:\n\n          -  Patient newly diagnosed with multiple myeloma, based on following IMWG 2014 definition\n             (Rajkumar et al 2014):\n\n          -  Clonal bone marrow plasma cells ? 10% or biopsy-proven bony or extramedullary\n             plasmacytoma and any one or more of the following myeloma defining events:\n\n          -  Evidence of end organ damage that can be attributed to the underlying plasma cell\n             proliferative disorder\n\n          -  Any one or more of the following biomarkers of malignancy:\n\n               1. Clonal bone marrow plasma cell percentage ? 60%\n\n               2. Involved: uninvolved serum free light chain ratio ? 100\n\n               3. >1 focal lesions on MRI studies\n\n          -  Patient with measurable disease defined by at least 1 of the following conditions\n             present at screening:\n\n          -  Serum M-protein by Protein Electrophoresis (PEP) ? 1.0 g/dL (? 10 g/L).\n\n          -  Urine M-protein by PEP ? 200 mg/24 hours. Involved serum free light chain level ? 10\n             mg/dL (? 100 mg/L), provided that the serum free light chain ratio is abnormal.\n\n          -  Patient eligible for autologous stem cell transplantation based on the investigator's\n             clinical judgment.\n\n          -  Patient with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ? 2\n\n          -  Patient's age ? 18 and <75 years at time of signing the informed consent\n\n          -  Patient provided written informed consent prior to any screening procedures\n\n          -  Women of childbearing potential (WOCBP) with a negative serum pregnancy test at\n             screening and a negative urine pregnancy test at baseline\n\n        Key Exclusion Criteria:\n\n        Patients eligible for this study must not meet any of the following criteria:\n\n          -  Any concomitant anti-cancer therapy (other than bortezomib/lenalidomide/dexamethasone;\n             bisphosphonates are permitted only if commenced prior to the start of screening\n             period)\n\n          -  Unresolved diarrhea ? CTCAE grade 2 or presence of medical condition associated with\n             chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).\n\n          -  Allogeneic stem cell transplant recipient presenting with graft versus host disease\n             either active or requiring immunosuppression\n\n          -  Patient shown intolerance to bortezomib or to dexamethasone or components of these\n             drugs or has any contraindication to one or the other drug, following locally\n             applicable prescribing information\n\n          -  Patient with rade ? 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain\n             on clinical examination at screening\n\n          -  Patient received prior treatment with DAC inhibitors including Panobinostat\n\n          -  Patient needing valproic acid for any medical condition during the study or within 5\n             days prior to first administration of panobinostat/study treatment.\n\n          -  Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted\n             only if commenced prior to the start of screening period)\n\n          -  Patient who received:\n\n               1. prior anti-myeloma chemotherapy or medication including Immunomodulator (IMiDs)\n                  and Dex ? 3 weeks prior to start of study.\n\n               2. experimental therapy or biologic immunotherapy including monoclonal antibodies ?\n                  4 weeks prior to start of study.\n\n               3. prior radiation therapy ? 4 weeks or limited field radiotherapy ? 2 weeks prior\n                  start of study.\n\n          -  Patient has not recovered from all therapy-related toxicities associated with above\n             listed treatments to < grade 2 CTCAE.\n\n          -  Patient undergone major surgery ? 2 weeks prior to starting study drug or who have not\n             recovered from side effects of such therapy to < grade 2 CTCAE\n\n          -  Patients with evidence of mucosal or internal bleeding\n\n          -  Clinically significant, uncontrolled heart disease and/or recent cardiac event (within\n             6 month prior to screening)\n\n          -  Inability to determine the Fridericia's Correction Formula (QTc) F interval\n\n          -  Patient with an impairment of gastrointestinal (GI) function or GI disease that may\n             significantly alter the absorption of panobinostat (e.g. ulcerative disease,\n             uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or\n             small bowel resection)\n\n          -  Sexually active males unless they use a condom during intercourse while taking the\n             drug during treatment, and for 6 months after stopping treatment\n\n          -  Pregnant or nursing (lactating) women.Xx_NEWLINE_xXSerum M-protein ? 0.5g/dL of IgA or ? 1 g/dL of IgG, orXx_NEWLINE_xXInvolved FLC assay > 10 mg/dL with abnormal FLC ratio.Xx_NEWLINE_xXSerum M-protein ? 0.5 g/dl (? 5 g/l)Xx_NEWLINE_xXSerum free light chains (FLC) assay: Involved FLC level ? 10 mg/dl (? 100 mg/l) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)Xx_NEWLINE_xXIf the serum protein electrophoresis is unreliable for routine M-protein measurement, quantitative immunoglobulin levels on nephrolometry or turbidometry will be followed.Xx_NEWLINE_xXSerum monoclonal protein ?1 g by protein electrophoresisXx_NEWLINE_xXSerum immunoglobulin free light chain ?10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXMust have measurable disease, defined by one or more of following: (i) a serum M protein > 0.5 g/dl measured by serum protein electrophoresis; (ii) urinary M protein excretion > 200 mg/24 hours; (iii) serum free light chain (FLC) measurement > 10 mg/dl, provided that the serum FLC ratio is abnormalXx_NEWLINE_xXSerum M-protein ? 0.5 g/dLXx_NEWLINE_xXSerum free light chain (FLC) > 100 mg/L of involved FLCXx_NEWLINE_xXA monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of ? 1.0 g/dL.Xx_NEWLINE_xXMeasurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ? 200 mg/24 hours.Xx_NEWLINE_xXInvolved serum free light chain (FLC) level ? 10 mg/dL, provided the serum FLC ratio is abnormal.Xx_NEWLINE_xXPresence of primary (light chain) amyloidosis.Xx_NEWLINE_xXMultiple myeloma showing signs of biochemical progression while taking lenalidomide or lenalidomide plus dexamethasone maintenance therapy after autologous hematopoietic stem cell transplantation; (progression is defined solely based on serum or urine M-protein, or in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved serum free light chain level)Xx_NEWLINE_xXPatients with biochemical progression only with at least >= 25% increase from the baseline in any of the following parameters on at least 2 occasions; and when the treating physician deems a change in therapy is necessary: a. serum M-protein; b. urine M-protein; or, c. in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved free light chain levelsXx_NEWLINE_xXPatients with relapsed or progressive multiple myeloma (progressive disease), defined as a 25 percent increase from the lowest response value in ANY of the following:\r\n* Serum M-protein (absolute increase >= 0.5 g/dL)\r\n* Urine M-protein (absolute increase of >= 200 mg/24 hours)\r\n* Bone marrow plasma cell percentage (at least 10 percent absolute increase) in patients who lack measurable M protein levels\r\n* Difference in the kappa and lambda free light chain (FLC) levels (FLC ratio must be abnormal and absolute change must be > 10 mg/dL)Xx_NEWLINE_xXPatients must have evaluable multiple myeloma with, at least one of the following, assessed within 21 days prior to randomization:\r\n* Serum M-protein >= 0.5 g/dL, or\r\n* Urine M-protein >= 200 mg/24 hour, or\r\n* In patients without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and/or an abnormal kappa/lambda ratio (> 4:1 or < 2:1), or\r\n* Monoclonal plasma cells in a bone marrow biopsy/aspirate of > 5 %Xx_NEWLINE_xXSerum M-protein ? 0.5 g/dL, orXx_NEWLINE_xXIn subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ratio (SFLC kappa lambda ratio < 0.26 or > 1.65)Xx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio\r\n* Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)Xx_NEWLINE_xXPatients must have clonal disease measureable by serum free light chain (FreeliteTM) assay:Xx_NEWLINE_xXFor the dose-escalation cohort: this is defined as having any elevation in the amyloidogenic (i.e. clonal) light chain with an abnormal free kappa:lambda ratioXx_NEWLINE_xXSubjects must have measurable disease, defined as one or both of the following:\r\n* Serum M-protein >= 1.0 g/dL\r\n* Urine M-protein >= 200 mg/24 hours\r\n* Free light chains: Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels must be at least 10 mg/dlXx_NEWLINE_xXMultiple myeloma (MM) diagnosed according to the following standard criteria (all three criteria must be met):\r\n* Monoclonal plasma cells in bone marrow >= 10% and/or presence of biopsy-proven plasmacytoma\r\n* Monoclonal protein (M-protein) present in serum and/or urine, defined as serum M-protein of >=1 g/dL OR urine M-protein of >= 200 mg/24 hours; patients with no M-protein must have serum free light chain assay with involved light chain >= 10 mg/dL and abnormal serum free light chain ratio\r\n* MM-related organ dysfunction (1 or more)\r\n** (C) calcium elevation in blood (serum calcium > 10.5 mg/L or upper limit of normal [ULN])\r\n** (R) renal insufficiency (serum creatinine [SCr] > 2 mg/dL)\r\n** (A) anemia (hemoglobin < 10 g/dL or 2g < normal)\r\n** (B) lytic bone lesions or osteoporosisXx_NEWLINE_xXMeasureable disease as indicated by monoclonal protein in the serum of greater than or equal to (?) 1 grams per deciliter (g/dL), involved serum free light chain assay ?10 mg/dL (?100 mg/L) provided the serum free light chain ratio is abnormal; monoclonal light chain in the urine protein electrophoresis of ? 200 mg/24 hours, or measurable plasmacytomaXx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1 g/dL\r\n* >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio\r\n* Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)Xx_NEWLINE_xXSerum M-protein ? 1.0 g/dLXx_NEWLINE_xXPatients must currently have measurable disease, as defined as:\r\n* Serum M protein >= 1.0 g/dl (>= 10000 mg/l) unless IgA >= 0.5 g/dL\r\n* Urine M protein >= 200 mg/24h\r\n* Serum free light chain assay: involved free light chain (FLC) level >= 10mg/dl (>= 100 mg/l) provided serum FLC ratio is abnormal\r\n* If no monoclonal protein is detected (non-secretory disease), then > 30% monoclonal bone marrow plasma cellsXx_NEWLINE_xXMeasurable disease of multiple myeloma as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 g/dL\r\n* > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXSerum M-protein ? 0.5 g/dL, orXx_NEWLINE_xXIn patients without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa/lamda ratio, orXx_NEWLINE_xXPatients with measureable disease defined as at least one of the following:\r\n* Serum M-protein >= 0.5 g/dl (>= 5 g/l)\r\n* Urine M-protein >= 200 mg/24 h\r\n* Serum free light chain (FLC) assay: involved FLC level >= 10 mg/dl (>= 100 mg/l) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)\r\n* Measurable plasmacytoma (prior biopsy is acceptable, should be measured within 28 days of first study drug administration)Xx_NEWLINE_xXHistologically confirmed diagnosis of multiple myeloma with a measurable disease parameter at time of screening; a measurable disease parameter is defined as one or more of the following:\r\n* Serum monoclonal protein >= 0.5 g/dl\r\n* 24 hour urine monoclonal protein >= 0.2 g/24 hour\r\n* Serum free light chain ratio > 5 x normal ratio with an absolute difference of 10mg/dl between the involved and uninvolved free light chain\r\n* Soft tissue plasmacytoma >= 2 cm measurable by either physical examination and/or applicable radiographs (e.g. magnetic resonance imaging [MRI], computed tomography [CT], etc)\r\n* Bone marrow plasma cells >= 30%Xx_NEWLINE_xXInvolved FLC ?10 mg/dL and abnormal FLC ratio in serum (<0.26 or >1.65)Xx_NEWLINE_xXInvolved FLC level ?10 mg/dL and abnormal FLC ratio in serum (<0.26 or >1.65)Xx_NEWLINE_xXInvolved FLC level ?10 mg/dL and an abnormal FLC ratio in serum (<0.26 or >1.65)Xx_NEWLINE_xXSerum M-protein ? 0.5 g/dLXx_NEWLINE_xXMeasurable monoclonal (M-) protein component in serum (? 0.5 g/dL) and/or urine (if present), (? 0.2 g excreted in a 24 hour collection sample). Subjects with free light chain only disease are excluded.Xx_NEWLINE_xXMyeloma-related organ dysfunction (at least one of the following) [C] Calcium elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin <10 g/dl or 2 g < laboratory normal) [B] Lytic bone lesions or osteoporosis AND have measurable disease by protein electrophoresis analyses as defined by the following:Xx_NEWLINE_xXIgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ? 1.0 g/dl or urine M-protein level ? 200mg/24hoursXx_NEWLINE_xXLight chain multiple myeloma: Serum M-protein level ? 1.0 g/dl or urine M-protein level ? 200 mg/24 hours AND are at least 65 years of age or older or, if younger than 65 years of age, are not candidates for stem cell transplantation because:Xx_NEWLINE_xXMeasurable disease of AL amyloidosis as defined by at least ONE of the following:\r\n* Serum monoclonal protein >= 1.0 by protein electrophoresis\r\n* > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\r\n* Free light chains (abnormal absolute value, ratio and the dFLC > 5 mg/dL)Xx_NEWLINE_xXPatients with multiple myeloma must have measurable disease; measurable disease may be paraprotein in serum or urine or the presence of free light chains in serum or urine defined by one or more of the following criteria: \r\n* Presence of serum M-protein concentration > 1 g/dL\r\n* Urine M-protein excretion > 200 mg in 24-hour urine collection\r\n* Serum free light chain concentration >= 10 mg/dL and abnormal kappa/lambda ratio\r\n* Urine free light chain concentration >= 100 mg/L and abnormal kappa/lambda ratioXx_NEWLINE_xXSerum M-protein ? 1.0 g/dL by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative IgA; orXx_NEWLINE_xXSerum FLC ? 100 mg/L, provided that the serum FLC ratio is abnormal.Xx_NEWLINE_xXIf serum protein electrophoresis is felt to be unreliable for routine M- protein measurement, then quantitative Ig levels by nephelometry or turbidometry are acceptable.Xx_NEWLINE_xXMM that does not express M-protein or serum FLC (i.e., non-secretory MM is excluded; plasmacytomas without M-protein or serum FLC are excluded).Xx_NEWLINE_xXParticipants must have confirmed high-risk monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) as defined below:\r\n* MGUS\r\n** Serum monoclonal protein level < 3 g/dL but > 1.5 g/dl\r\n** Non-immunoglobulin (Ig)G MGUS (i.e. IgA, IgM, IgD MGUS)\r\n** Abnormal serum free light chain ratio (i.e. ratio of kappa to lambda free light chains < 0.26 or > 1.65)\r\n* SMM (also referred to as asymptomatic multiple myeloma)\r\n** Serum monoclonal protein (IgG or IgA) level >= 3 g/dL,\r\n** And/or bone marrow plasma cells >= 10%\r\n** Absence of end-organ damage, such as lytic bone lesions, anemia, hypercalcemia, or renal failure, that can be attributed to a plasma cell proliferative disorderXx_NEWLINE_xXDiagnosis of any stage of multiple myeloma based on standard criteria as follows:\r\n* Major criteria\r\n1. Plasmacytomas on tissue biopsy\r\n2. Bone marrow plasmacytosis (> 30% plasma cells)\r\n3. Monoclonal immunoglobulin spike on serum electrophoresis (immunoglobulin G [IgG] > 3.5 G/dL or immunoglobulin A [IgA] > 2.0 G/dL) or kappa or lambda light chain excretion > 1 G/day on 24 hour urine protein electrophoresis\r\n* Minor criteria\r\na. Bone marrow plasmacytosis (10 to 30% plasma cells)\r\nb. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria\r\nc. Lytic bone lesions\r\nd. Normal immunoglobulin M (IgM) < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL\r\n* Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:\r\n** Any two of the major criteria\r\n** Major criterion 1 plus minor criterion b, c, or d\r\n** Major criterion 3 plus minor criterion a or c\r\n** Minor criteria a, b and c or a, b and dXx_NEWLINE_xXNonsecretory multiple myeloma based upon standard M-component criteria (ie, measurable serum/urine M-component) unless the baseline serum free light chain level is elevatedXx_NEWLINE_xXMM\r\n* Absence of monoclonal protein in serum and urine by immunofixation with no current evidence of soft tissue plasmacytoma\r\n* Bone marrow aspirate and biopsy must demonstrate less than 5 percent clonal plasma cells\r\n* In patients who lack measurable M proteins in the serum and urine being monitored using the free light chain (FLC) levels, the definition of complete response (CR) requires a normalization of the FLC ratio in addition to the above criteriaXx_NEWLINE_xXPart 1/dose escalation; Histologically or cytologically confirmed diagnosis of Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy. Part 2 /MM cohort; Histologically or cytologically confirmed diagnosis of: Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy, and has measurable disease with at least one of the following: serum M-protein >=0.5 gram (g)/decilitre (dL) (>=5 g/Litre (L)), urine M-protein >=200 milligram (mg)/24hour (h). Serum free light chain (FLC) assay: Involved FLC level >=5 mg/dL (>=50 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65) and biopsy proven plasmacytoma (should be measured within 28 days of Screening Visit).Xx_NEWLINE_xXDiagnosis of high risk smoldering multiple myeloma (SMM) (per International Myeloma Working Group [IMWG] criteria) for less than or equal to (<=)5 years with measurable disease, defined as clonal bone marrow plasma cells (BMPCs) greater than or equal to (>=)10 percent (%) but less than (<)60% and 1 of the following: serum M-protein >=10 gram per liter (g/L) or urine M-protein >=200 milligram per 24 hours (mg/24 hours) or involved serum free light chain (FLC) >=100 milligram per liter (mg/L) and abnormal serum FLC ratioXx_NEWLINE_xXSerum FLC ratio (involved:uninvolved) >=100 (the involved FLC must be >=100 mg/L)Xx_NEWLINE_xXPrimary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosisXx_NEWLINE_xXSerum M-protein ? 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative serum IgA levels; orXx_NEWLINE_xXSerum free light chain (FLC) ? 100 mg/L, provided that the serum FLC ratio is abnormal.Xx_NEWLINE_xXDocumented systemic light chain amyloidosis.Xx_NEWLINE_xXMeasurable disease based on either of a) serum monoclonal protein by protein electrophoresis (SPEP), b) monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP), and/or c) serum immunoglobulin free light chain combined with abnormal serum immunoglobulin kappa to lambda free light chain ratioXx_NEWLINE_xXSerum M-protein >=500 mg/dL (>=5 gram per liter [g/L]).Xx_NEWLINE_xXIn participants without measurable M-protein in serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP), a serum FLC assay result with involved FLC level >=10 mg/dL (>=100 milligram per liter [mg/L]), provided serum FLC ratio is abnormal.Xx_NEWLINE_xXEvaluable disease (serum protein electrophoresis [SPEP]/urine protein electrophoresis [UPEP]/serum free light chain [SFLC] criteria)Xx_NEWLINE_xXMeasurable disease defined by one of the following:\r\n* Serum monoclonal protein >= 0.5 g/dL by serum protein electrophoresis (SPEP)\r\n* >= 200 mg/monoclonal protein in urine on 24 hr urine protein electrophoresis (UPEP)\r\n* Serum free light chain (FLC) >= 10 mg/dL and abnormal serum kappa to lambda ratio\r\n* Plasma cytomas that are palpable per exam or measurable per standard radiologic review\r\n* Circulating plasma cells >= 2,000 if diagnosis of plasma cell leukemiaXx_NEWLINE_xX