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 hr
Patient 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%
RE-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%
Inclusion 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.
Serum free light chain ? 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
Patients 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%
Disease 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)
Measurable 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 ratio
Patients 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 aspiration
Involved/un-involved light chain ratio must be < 100
Measurable 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])
Serum free light chain assay: involved free light chain level > 10 mg/dL (> 100 mg/L) provided the serum free light chain ratio is abnormal
Serum free light chain (SFLC) ? 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
Measurable 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 ratio
Patients 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.
Have 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%
Patients 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)
Evaluable 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;
Diagnosis 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 ratio
Measurable 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)
Measurable 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)
Measurable 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 hr
Patients 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 ratio
Nonsecretory 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 imaging
M spike >= 0.5 g/dL or involved free light chain >= 10 mg/dL with an abnormal free light chain ratio
serum 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/ dL
Measurable 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 abnormal
High 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/dL
Presence 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 marrow
Subjects 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 criteria
Subjects 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 range
Patients 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 marrow
Measurable 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 ratio
Participants with light chain and free light chain (FLC) only may be enrolled if they meet all the criteria for a diagnosis of MM.
in 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 ratio
Subject 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.
Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning).
Measurable 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 consent
Measurable 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).
Subjects 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 ratio
Patients 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)
Had 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) discretion
Must 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%
Patients 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 measurements
Criteria 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 MM
Inclusion 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.
Measurable 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.
Must have measurable disease as defined by m-protein or serum free light chain.
Measurable 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.
Serum free light chain (SFLC): involved FLC ?10 mg/dL (?100 mg/L) AND abnormal kappa to lambda serum free light chain ratio
Abnormal serum free light-chain ratio ?100 (involved kappa) or < 0.01 (involved lambda)
Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory).
Free Light Chain measurable disease only.
Absence of involved: uninvolved serum free light chain ratio >= 100
Participants 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) ratio
In 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 ratio
Participants 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) ratio
Patients 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)
Patients 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 abnormal
Measurable 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 ratio
Patients 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)
For 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 abnormal
Measurable 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 100
Patients 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/dL
Patients with light chain only myeloma are eligible; the involved free light chain level >= 100 mg/L with abnormal serum free light chain ratio
Patients 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.
Protein 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 enrollment
Non-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 chain
Patients 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 abnormal
Measurable 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 cohort
Diagnosis 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)
Serum monoclonal protein >0.5g/dL and/or 0.2g/24hr urine light chain excretion
Relapsed/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.
Subjects with non-secretory or oligo-secretory or serum free light-chain only myeloma
Demonstrate 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) ratio
Must 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.
Measurable disease defined as at least one of the following: Serum m-spike >= 1g/dL, urine m-spike >= 200mg/24hrs, serum free light chains >= 100mg/L (provided the kappa/lambda ratio is abnormal), or bone marrow plasma cells >= 30%
Patients 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.
Patients 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 serum
Monoclonal 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 plasmacytoma
Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ? 200 mg/24 hours.
Multiple 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)
Patients 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 levels
Patients 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)
Patients 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 %
In 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)
Patients must have clonal disease measureable by serum free light chain (FreeliteTM) assay:
For 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 ratio
Subjects 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/dl
Multiple 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 osteoporosis
Measureable 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 plasmacytoma
In 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, or
Histologically 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%
Measurable 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.
Patients 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 ratio
Nonsecretory multiple myeloma based upon standard M-component criteria (ie, measurable serum/urine M-component) unless the baseline serum free light chain level is elevated