Urine protein: creatinine (UPC) ratio < 1 or urine dipstick for proteinuria =< 2+ (note: if the UPC ratio is >= 1.0 then a 24-hour urine collection should be performed and this must demonstrate =< 1g of protein in 24 hours)
Proteinuria at screening as demonstrated by urinalysis with proteinuria ? 2+ (patients discovered to have ?2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ? 1g of protein in 24 hours to be eligible).
Proteinuria with urinary protein is =< 1+ on dipstick or routine urinalysis, or a 24-hour urine collection for protein < 1000 mg of protein in 24 hours, within 28 days prior to administration of study treatment
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
Baseline urinalysis should show urine protein < 3+ and must be obtained within 28 days prior to registration; if urine protein is 3+ or greater, then urine protein by 24 hour collection must show less than 3 grams of protein
Within 2 weeks prior to registration: Screening urine dipstick must equal 0 or “trace”; if urine dipstick results are >= 1+, or if dipstick was not performed, calculation of urine protein creatinine (UPC) is required and patients must have a UPC ratio =< 1 to participate in the study
Urine protein creatinine (UPC) =< 1; if UPC >= 1, then a 24-hour urine protein must be assessed; eligible patients must have a 24-hour urine protein value < 1 g/L
Within 14 days prior to registration: Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended (24-hour urine protein level must be < 1000 mg for patient enrollment); UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion – a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
Participants 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)
A urine sample tested for proteinuria by the dipstick method must indicate 0 -1+ protein; if dipstick reading is >= 2+, a 24-hour urine specimen must demonstrate < 1.0 g of protein per 24 hours
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%
Urine protein: =< 30 mg/dl in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour (h) urine sample
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.
Participants having greater than 1+ proteinuria on urinalysis will undergo 24-h urine collection for quantitative assessment of proteinuria. Participants with urine protein greater than or equal to 1 g/24-hour will be ineligible.
Urine protein to creatinine ratio < 1 OR 24-hour urine protein < 1 g
Urine Protein to Creatinine Ratio (UPC) < 1
Proteinuria as demonstrated by a urine protein:creatinine (UPC) ratio >= 1.0 at screening, or urine dipstick for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible)
Inclusion 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.
Serum M-Protein >=1.0 g/dL (>=10 g/L), OR
Urine M-Protein >= 200 mg/24 hours, OR
Serum 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.
Urinary protein is > 1 + on dipstick and the required following 24-hour urine collection shows urinary protein > 2000 mg;
Urine protein-creatinine ratio (UPCR) =< 1 on spot urinalysis or protein =< 500 mg/24 hour urine
Serum M- protein ?0.5 g/dL for IgG, IgM, IgA, or ?0.05 g/dL for IgD; or
Urine M-protein ?200 mg/24 hours ; or
Serum monoclonal protein ? 0.5 g/dL by protein electrophoresis.
? 200 mg/24 hours of monoclonal protein in the urine on 24-hour electrophoresis
Serum free light chain ? 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
Urine protein to creatinine ratio of < 1, a urinalysis that is negative for protein, or a 24-hour urine protein level < 1000 mg/dL
Urinary protein =< 1+ on dipstick or routine urinalysis (if urine dipstick or routine urinalysis is 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours)
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)
Patients 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)
Progressive disease defined by any of following: 25% increase in serum M-protein from lowest response value during (or after) last therapy and/or absolute increase in serum M-protein of > or equal to 0.5 g/dL; 25% increase in urine M-protein from lowest response value during (or after) last therapy and/or absolute increase in urine M-protein of > or equal to 200 mg/24h; 25% increase in bone marrow plasma cell percentage from lowest response value during (or after) last therapy - absolute bone marrow plasma cell percentage must be > or equal to 10% unless prior complete response when absolute bone marrow plasma cell percentage must be > or equal to 5%; 25% increase in serum FLC level from the lowest response value during (or after) last therapy - the absolute increase must be > 10 mg/dL; new onset hypercalcemia > 11.5 mg/dL
Measurable 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 basis
Spot urine total protein:creatinine ratio >1,000 mg/gm
Urine protein: creatinine ratio =< 1, within 14 days before the first dose of cabozantinib
Measurable serum and/or urine M-protein from prior to induction therapy documented and available; a positive serum free lite assay is acceptable
Proteinuria =< 2+ by urinalysis or urine dipstick
Urine protein/creatinine ratio of less than 1
Urine protein via dipstick =< 2+ or =< 100 mg/dl
Patients with central pulmonary metastases or recent hemoptysis (>= 1/2 tea spoon [tsp] of red blood) within 28 days of registration\r\n* Patients with clinically significant proteinuria (i.e. > grade 1) or urine protein to creatinine ratio (UPC) ratio above 1.0\r\n* Patients with suspicion of transmural tumor bowel involvement based on the investigator's discretion may not enroll on this study
Measurable 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 abnormal
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
Urine protein to creatinine ratio (UPCR) =< 1 within 7 days before the first dose of cabozantinib
Urine M-protein level >= 200 milligram per 24 hours (mg/24 hours); or
Light 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 ratio
Measureable 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 ratio
Key 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 therapy
High-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)
Participants with proteinuria >1+ on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ?1 g/24 hour will be ineligible.
Urinary protein =< 1+ on dipstick or routine urinary analysis (UA); if dipstick or routine UA is >= 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours
Proteinuria as demonstrated by a urine protein to creatinine ratio (UPCR) of >=1.0 at screening
Urine protein: =< 30 mg/dl in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour (h) urine sample
Urine protein/creatinine ratio (UPCR) =< 1
Patient 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].
Serum M-protein defined by the following:
IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ?1.0 g/dL (measured by protein electrophoresis [PEP]);
Urine M-protein ?200 mg/24 hours (any immunoglobulin heavy chain type measured by PEP).
Serum free light chain (FLC) ?10 mg/dL with abnormal ratio in subjects with unmeasurable disease by serum or urine PEP.
Measurable disease M protein component in serum (at least 0.5 g/dL) and/or urine (if present) (>=0.2 g excreted in a 24 hour collection sample).
Patients with proteinuria within 14 days of registration as demonstrated by either: urine protein creatinine (UPC) ratio >= 1.0 at screening OR urine dipstick for proteinuria 2+ (patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection, and must demonstrate =< 1 g of protein/24 hours to be eligible)
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
Measurable 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 abnormal
Persistent proteinuria >= grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hours [hrs], measured by urine protein:creatinine ratio on a random urine sample)
Urine protein <500 mg or urine protein: creatinine ratio (UPC) <1.0; and
Persistent proteinuria >= grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample)
Patients 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 ratio
Measurable 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
COHORT B ONLY: serum immunoglobulin free light chain >= 5 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
Measurable 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.
Urine protein to creatinine ratio =< 1 (if urine protein creatinine ratio is > 1, then a 24-hour urine total protein must be assessed; subjects will be ineligible if the 24-hour urine protein is found to be > 1 gm)
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* 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 criteria
Urine protein:creatinine ratio >= 1.0 at screening
Documented baseline proteinuria > 1000 mg/day on 24 hour urine collection; only patients with 1+ or greater proteinuria on urinalysis (UA) and a spot urine protein: creatinine ratio of > 0.5 will undergo a 24 hour urine collection for quantitation of proteinuria
Urine protein / creatinine ratio (UPCR) =< 1
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])
Measurable 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
Have 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%
Serum M-protein > 0.5 g/dL
Urine M-protein > 200 mg/24 hours
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 monoclonal protein ? 0.5 g/dL by serum protein electrophoresis (SPEP)
? 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP)
Serum free light chain (SFLC) ? 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
Subjects having > 1+ proteinuria on urine dipstick testing will undergo 24 hours (h) urine collection for quantitative assessment of proteinuria; subjects with urine protein >= 1 g/24h will be ineligible
Patients 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 electrophoresis
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
Has greater than 1+ proteinuria on a urine dipstick or equivalent routine laboratory analysis will require further testing with a urine protein to creatinine ratio (UPCR); UPCR must be calculated as follows: UPCR = protein concentration (mg/dL)/creatinine (mg/dL); if the UPCR >= 1, then the patient will not be eligible for study entry; however, if urinalysis or equivalent routine laboratory analysis shows no protein, then UPCR testing is not required
Additional inclusion criteria for patients on the arm pembrolizumab plus ramucirumab:\r\n* Urinary protein is < 100 mg/dL on routine urinalysis. If urine routine urinalysis indicates proteinuria >= 100 mg/dL, then a 24-hour urine collection must be performed and must demonstrate urine protein < 2 g to allow the patient to participate in the study.
Within 28 days prior to administration of study treatment: Urine protein: creatinine ratio (UPC) of =< 1
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.
Urine protein to creatinine (UPC) ratio =< 1
Obtained within 28 days prior to the first dose of cabozantinib: urine protein/creatinine ratio (UPCR) =< 1.
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)
Urine protein/creatinine ratio (UPCR) =< 1
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;
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)
Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or
Light 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 ratio
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
Measurable 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 ratio
Within 7 days before the first dose of study treatment: Urine protein to creatinine ratio (UPCR) =< 1
Patients 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 ratio
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
Obtained within 14 days prior to the first study treatment (cycle 1, day 1): urine dipstick for proteinuria < 2+ unless a 24-hour urine protein =< 1g of protein is demonstrated
(Bevacizumab-related exclusion) Proteinuria as demonstrated by a urine protein:creatinine (UPC) ratio >= 1.0 at screening
Serum M-protein ?1 g/dL (?10 g/L), OR
Urine M-protein ?200 mg/24 hours and must have documented MM isotype by immunofixation (central laboratory).
Urine protein =< 1+ or =< 30 mg/dL OR urine protein/creatinine ratio =< 1, performed within 10 days of treatment initiation
Within 14 days prior to cycle 1 day 1 of treatment: Urinary albumin excretion < 1.0 g/24 hours (as estimated by urine protein-creatinine ratio)
FOR ALL PHASES (Ib AND II): Proteinuria of >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 as estimated by urine protein : creatinine ratio > 3.5 on a random urine sample
Serum M-protein ? 0.5 g/dL OR
Urine M-protein ? 200 mg/24 hours OR
Urine protein creatinine (UPC) ratio of < 1
Persistent proteinuria >= grade 3 per NCI-CTCAE v4.0 (> 3.5 g/24 hours [hrs], measured by urine protein: creatinine ratio on a random urine sample)
Participants 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 ratio
Participants 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 ratio
M spike >= 0.5 g/dL or involved free light chain >= 10 mg/dL with an abnormal free light chain ratio
Persistent proteinuria >= grade 3 NCI-CTCAE version (v) 4.0 (> 3.5 g/24 hours [hrs], measured by urine protein: creatinine ratio on a random urine sample)
Within 14 days prior to the first study treatment (cycle 1, day 1): Urine dipstick for proteinuria < 2+ or 24-hour urine protein < 1 g of protein is demonstrated
Proteinuria as demonstrated by a urine protein:creatinine (UPC) ratio >= 1.0 at screening
Urine protein =< 30 mg/g
serum 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)
Urine protein/ creatinine ratio (UPCR) =< 1
Urine Protein to Creatinine Ratio (uPCR) < 2.0
If uPCR ? 2.0 then a 24-hour urine collection can be performed to qualify. If this is performed to qualify, the protein result must be < 2 g per 24 hours.
A urine protein:creatinine ratio of < 1 or < 1 g protein on 24-hour urine collection
FOR 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 ratio
Measurable 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)
Measurable 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
Urine protein/creatinine ratio =< 1 OR 24-hour urine protein < 1.5 gram obtained =< 14 days prior to registration
Urine protein/creatinine ratio =< 1
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
Non-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 Freelite
Urine/protein creatinine ratio spot-check < 0.5 mg/mg
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
> 30 mg/dL on urine analysis; patients with > 30 mg/dL on urine analysis on urine analysis will undergo 24-hour urine collection for quantitative assessment of proteinuria; subjects with 24-hour protein >= 1 g/24 hours will be ineligible
For 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.
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
Urine protein =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour urine sample
Urine protein creatine ratio (UPCR) < 1 prior to enrollment
Urine protein by dipstick <1+ or UPC =< 1.0 by urinalysis
Urinary protein < 2+ by urine dipstick (if dipstick is >= 2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is < 2 g per 24 hours)
Have 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%
The patient’s urinary protein is =< 1+ on dipstick or routine urinalysis (urine analysis [UA]; if urine dipstick or routine analysis is >= 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in this protocol)
Patients 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)
Measurable 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
Proteinuria > 2.0 g of protein in a 24-hour urine collection; all patients with 2 protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein
Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein must be obtained and must be < 1000 mg
Proteinuria of CTCAE grade 3 or higher (> 3.5 g/24 h, measured by urine protein: creatinine ratio on a random urine sample)
REGORAFENIB EXCLUSION CRITERIA: Persistent proteinuria >= grade 3 (> 3.5 g/24 hours [hrs], measured by urine protein:creatinine ratio on a random urine sample)
Subjects 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 ratio
Subjects 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 disorder
Urine protein > 2+; Patients discovered to have ? 1+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24-hour urine;
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
Urine dipstick for proteinuria < 2+ unless a 24-hour urine protein < 1 g of protein is demonstrated
Proteinuria at baseline; subjects unexpectedly found to have >= 2+ proteinuria on a urine dipstick at baseline should undergo a 24-hour urine which must be an adequate collection and must demonstrate < 2 g of protein/24 hour (hr) to allow participation in the study
The patient’s urinary protein is =< 1 positive (+) (=< 30-100 mg/dl) on dipstick or routine urinalysis (urinary analysis [UA]; if urine dipstick or routine analysis is >= 2+ (>=100-300 mg/dl), a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in this protocol)
Have 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 hours
Urine protein/creatinine ratio (UPCR) =< 1
Proteinuria > 100 mg/dl on urine analysis
Urinalysis: for patients with 2+ proteinuria on urinalysis, 24 hour urine collection should be obtained; 24 hour urine protein should be < 2 grams
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
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nSpot urine protein/creatinine ratio =< 1 OR 24 hour urine protein =< 1000 mg
PHASE II COLORECTAL CANCER COHORT 6 (MEDI+C ONLY):\r\nSpot urine protein/creatinine ratio =< 1 OR 24 hour urine protein =< 1000 mg
Proteinuria =< grade 1 (ie, =< 1+ [30 mg/dL] using a random urine sample or < 1.0 gm using a 24-hour sample)\r\n* Note: if urine sample indicates >= grade 2 proteinuria (ie, 2+ [100 mg/dL]), a 24-hour urine sample must be collected and tested; urine protein in the 24-hour sample must be < 1.0 gm/24 hours
Urine protein: creatinine ratio (UPC) of =< 1 or less than or equal to 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart; UPC is the preferred test; patients with >= 2+ proteinuria on dipstick must also have a 24 hour urine collection demonstrating =< 500 mg over 24 hours
Urine dipstick for proteinuria < 2+; patients discovered to have >= 2+ proteinuria on dipstick should undergo a 24-hour urine collection and demonstrate =< 1g of protein in 24 hours
Urine M protein ? 200 mg/24 hours), or
Serum immunoglobulin free light chains ? 10 mg/dL and abnormal serum immunoglobulin kappa/lambda free light chain ratio), or
Within 4 days prior to the first dose of cabozantinib: Urine protein/creatinine ratio (UPCR) =< 1
Urine protein < 2+
If urinalysis shows proteinuria, 24 hour urine collection is to be performed and the 24 hour urine protein is to be < 2 grams to be eligible
Patients who have proteinuria at baseline; patients who are unexpectedly discovered to have >= grade 2 proteinuria at baseline routine urinalysis should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate =< 1 g of protein/24 hour (hr) to allow participation in the study
Urine protein creatinine (UPC) < 1 or, if UPC >= 1, 24-hour urine protein < 1 g; use of urine dipstick for renal function assessment is not acceptable
Urine protein should be screened by dipstick or urine analysis; for proteinuria > 1+ or urine protein: creatinine ratio > 1.0, 24-hour urine protein should be obtained and the level should be < 2000 mg for patient enrollment
Urine protein/creatinine ratio (UPCR) =< 1
Urine protein creatinine ratio as determined by urinalysis of < 0.5 (for urine protein creatinine ratio of > 0.5, 24-h urine protein must have been < 1 gram)
Proteinuria as demonstrated by: \r\n* Urine protein: creatinine (UPC) ratio >= 1.0 at screening OR \r\n* Urine dipstick for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible)
Measurable 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 therapy
Urine M-protein =< 1 g/24 hours (MM patients only)
Urine protein/creatinine ratio (UPCR) =< 1
Patients 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 values
Urine protein:creatinine ratio >= 1.0 at screening
Urine protein : creatinine ratio >= 1.0 at screening
Urine for proteinuria should be < 2 +; patients discovered to have >= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours
In patients with metastatic pheochromocytoma, screening urinalysis required prior to study enrollment; if random collection urine specimen is positive for proteinuria, patients must have 24-hour urine protein determination; patients with metastatic pheochromocytoma are excluded if 24-hour urine protein is above the institutional upper limit of normal
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
Urine protein to creatinine ratio (UPC) < 1; if UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
Or 24-hour urine protein < 1 g
Urine protein should be screened by urine analysis; if protein is 2+ or higher, 24-hour urine protein should be obtained; patients with 24-hour urine protein >= 1000 mg are excluded
Patients 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 ratio
Urine protein < 1+ on dipstick test or routine urinalysis; if the proteinuria on these tests is >= 2+, then a 24-hour urine test must be collected and must demonstrate < 1 g protein in 24 hours to allow participation
Proteinuria as demonstrated by:\r\n* Urine protein: creatinine (UPC) ratio >= 1.0 at screening (patients discovered to have a UPC >= 1 should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible) OR\r\n* Urine dipstick for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis may either undergo urine protein: creatinine (UPC) testing, and may participate if ratio < 1. 0 or should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible)
If there is proteinuria present on dipstick, patients must have a 24 hour urine collection; patients are excluded if they have > 500 mg protein on 24 hour urine collection
Urinary protein < 2+ by urine dipstick (if >= 2+, a 24-hour urine protein must show protein < 2 g per 24 hours)
Proteinuria at screening as demonstrated by either urine protein: urine protein creatinine (UPC) ratio >= 1.0 or 24hr collection > 1g/24hr at screening
Urinary protein excretion =< 500 mg/day
serum M-protein ?1 gm/dL (?10 gm/L).
urine M-protein ?200 mg/24 hours.
Measurable 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
Serum M-protein ?1 g/dL (?0.5 g/dL in case of immunoglobulin A [IgA] disease), AND/OR
Urine M-protein ?200 mg/24 hours, OR
In 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).
urine M-protein ? 200 mg/24 hours,
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
Urinary protein >2+ possibly indicative of renal disease. If the 24 hours urine protein shows a result of < 100 mg protein, subject can be eligible;
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
Urine protein to creatinine ratio (UPC) < 1; NOTE: if UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
Presence of serum and/or urinary monoclonal protein
Serum M-protein ? 1 g/dL
Urine M-protein ? 200 mg/24h
One 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).
Measurable 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 abnormal
The 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).
Must 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).
Urine protein =< 1+ or urine protein to creatinine ratio =< 1; if urine protein:creatinine (UPC) ratio is > 1 on urinalysis, then 24-hour urine collection from protein must be obtained and level must be < 1,000 mg for patient enrollment
Urine dipstick proteinuria >= 2+ or nephrotic range proteinuria on >= 2 gram in 24-hour urine
Within 7 days before the first dose of cabozantinib: Urine protein/creatinine ratio (UPCR) =< 1
Patients 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.
Urine for proteinuria should be < 2 +; patients discovered to have >= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24?hour urine collection and must demonstrate < 1 g of protein in 24 hours
Persistent proteinuria >= grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample)
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).
Urine dipstick proteinuria < 2+ or urine protein/creatinine (UPC) ratio =< 1.0; Note: patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate =< 1 g of protein in 24 hours
Measurable 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 ratio
Urine protein:creatinine ratio (UPC) =< 45 mg/mmol; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)
Urine protein/creatinine ratio (UPCR) =< 1
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
Subjects 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 disorder
Proteinuria =< 2+ (100 mg/dL) using a random urine sample or < 3.0 gm using a 24-hour sample; Note: If urine sample indicates >= 2+ [100 mg/dL]), a 24-hour urine sample must be collected and tested; urine protein in the 24-hour sample must be < 3.0 gm/24 hours
Serum monoclonal protein ? 0.5 g/dL
Urine monoclonal protein >200 mg/24 hour
Serum immunoglobulin free light chain >10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)
Serum M protein ? 0.5 /dL (? 5 g/L)
Urine M protein ? 200 mg/24 hours
Within 28 days prior to administration of therapy: Proteinuria - urine protein:creatinine ratio (UPC) of =< 1 OR =< 2+ proteinuria on two consecutive urinalysis/dipstick tests taken no less than 1 week apart; patients with 2+ proteinuria on dipstick must also have a UPC of =< 0.5 on 2 consecutive samples
Urine protein: creatinine ratio (UPC) of =< 1; UPC is the preferred test
Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h
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)
Urine protein: creatinine ratio urine protein creatinine (UPC) of =< 1 OR less than or equal to 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart; UPC is the preferred test; patients with 2+ proteinuria on dipstick must also have a 24-hour urine collection demonstrating protein of =< 500 mg over 24 hours
Measurable level of M-protein > 1 g/dL on serum protein electrophoresis or > 200 mg of M-protein on a 24 hour urine protein electrophoresis
Urine protein-creatinine ratio (UPCR) =< 1 on spot urinalysis or protein =< 500 mg/24 hour urine
Absence of proteinuria at screening as demonstrated by one of the following:\r\n* Urine protein/creatinine (UPC) ratio < 1.0 at screening OR\r\n* Urine dipstick for proteinuria < 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible)
Proteinuria at Screening. Subjects with a urine dipstick protein ?2+ at Screening should undergo a 24-hour urine collection and must demonstrate ?1g of protein in 24 hours to be eligible
Urine protein/creatinine ratio (UPCR) =< 1
Patient 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)
Measurable 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
Patients 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 range
Proteinuria >= grade 3 (> 3.5 g/24 hours, measured by urine protein: creatinine ratio on a random urine sample)
Proteinuria: if urine dipstick shows 2+ protein, 24 hour urinary protein should be done and be less than =< 2 grams/24 hours
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
Patients 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 plasmacytoma
Urine protein should be screened by urinalysis; if protein is 2+ or higher, 24 hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment
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 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 followed
Patients must have measurable disease within 28 days prior to registration; patients must have serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) within 14 days prior to registration
Urine protein/creatinine ratio (UPCR) =< 1; if urine/protein creatinine (UPC) >= 1, then a 24-hour urine protein must be assessed; eligible patients must have a 24-hour urine protein value < 1 g/L
Measurable disease defined as a quantitative IgM monoclonal protein of >500\n                  mg/dL obtained within 28 days prior to registration
Urine protein/creatinine ratio < 1 or 24-hour urine < 1 gram
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
Spot urine protein to creatinine ratio (UPCR) < 1 or a 24-hour urine protein collection < 1 gm within 10 days prior to registration
Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment
Urine protein must be screened by urine analysis within 28 days prior to registration; patient must not have greater than +1 proteinuria on two consecutive dipsticks taken no less than 7 days apart; however, if the first urinalysis shows no protein, then a repeat urinalysis is not required
Patients with clinically significant proteinuria (urine protein creatinine ratio greater or equal to 1.0)
Proteinuria at screening as demonstrated by either:\r\n* Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR\r\n* Urine dipstick for proteinuria > 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is < 1.0 to be eligible; if the UPC ratio is >= 1.0 then the patient should undergo a 24-hour urine collection which must demonstrate =< 1 g of protein in 24 hours for the patient to be eligible)
Participants 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 inclusion
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.
This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients must have a urine protein-to-creatinine ratio (UPCR) < 1.0 mg/dL
Patients must have measurable levels of monoclonal protein (M-protein): >= 1g/dL on serum protein electrophoresis or >= 200 mg of monoclonal protein on a 24 hour urine protein electrophoresis which must be obtained within 4 weeks prior to randomization
Urinary protein is <2+.
Subjects 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 agents
Urine protein/creatinine (UPC) ratio < 0.5 or urine protein =< 1+ on dipstick or routine urinalysis (UA); if UPC >= 0.5 or urine dipstick or routine analysis is >= 2+, a 24-hour urine collection for protein must demonstrate < 1,000 mg of protein in 24 hours to allow participation in the study
Patients 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 ratio
Urine protein/creatinine ratio =< 1 (or protein =< 1+ on urinalysis or 24 hour urine protein =< 1 gram/24 hours)
Urine protein to urine creatinine ratio (UPC) should be less than 1; if greater than 1, then 24 hour urine protein must be less than 1 g for patient to be eligible
Patients whose urinary protein is =< 1+ on a dipstick or routine urinalysis (UA); if routine analysis is > 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in this protocol)
Participant 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)
Subjects must have a urine protein/creatinine (UPC) ratio < 1; if UPC >= 1, then a 24-hour urine total protein must be obtained; subjects must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
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.
Have urinary protein ?1+ on dipstick or routine urinalysis.
Urine protein creatinine (UPC) < 1 (in like units) or, if UPC >= 1, 24-hour urine protein < 1 g; use of urine dipstick for renal function assessment is not acceptable
Urine protein/creatinine ratio (UPCR) =< 1
Serum monoclonal protein (SPEP) ?1 g/dL
Urine M-protein ?200 mg/24 hrs
Serum free light chain (SFLC): involved FLC ?10 mg/dL (?100 mg/L) AND abnormal kappa to lambda serum free light chain ratio
Urine protein creatinine (UPC) ratio < 1 OR urine protein =< 1+
Monoclonal protein present in the serum and/or urine
IgG MM: Serum monoclonal paraprotein (M-protein) level ? 1.0 g/dl or urine Mprotein level ? 200 mg/24 hours- IgA MM: Serum M-protein level ? 0.5 g/dl or urine M-protein level ? 200 mg/24 hours
IgM MM (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 ? 200 mg/24 hours
IgD MM: Serum M-protein level ? 0.05 g/dl or urine M-protein level ? 200 mg/24 hours
Light 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:
Participants having > 1 + proteinuria on urine dipstick testing will undergo 24 hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ? 1 gram/24 hours will be ineligible.
Serum M protein ?0.5 g/dL (?5 g/L);
Urine M protein ?200 mg/24 hours;
Urine protein/creatinine ratio >= 1.0
Patients are excluded if they have proteinuria at screening as demonstrated by either:\r\n* Urine dipstick for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible) OR\r\n* Urine protein: creatinine (UPC) ratio >= 1.0 at screening; for UPC ratio > 1, a 24 hour urine protein should be obtained and the level should be < 1000mg; NOTE: urine protein should be screened by urine analysis for UPC ratio; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 g
Urinalysis dipstick for urinary protein performed within 28 days prior to randomization must be 0-1+ protein. If urine dipstick result is greater than or equal to 2+ protein, a 24-hour urine protein must be less than 1.0 g/24 hours.
Serum monoclonal protein (SPEP) ?1 g/dL.
Urine monoclonal protein (UPEP) ?200 mg by 24 hour urine.
Must have measurable disease (serum M-protein or urine M-protein).
Urine protein: creatinine ratio ? 1.0 at screening
Have persistent 2+ protein by urinalysis (patients with 2+ proteinuria that have a spot protein:creatinine ratio of less than 0.3 may be enrolled) or a history of nephrotic syndrome.
Serum monoclonal protein ? 0.5 g/dL by protein electrophoresis
?200 mg of monoclonal protein in the urine on 24-hour electrophoresis
Serum immunoglobulin free light chain ?10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
Prior treatment with TRC105 or axitinib or any agent targeting the endoglin pathway (including a fusion protein that binds bone morphogenic protein)
Measurable levels of myeloma paraprotein (M-protein) in serum (> 0.5 g/dL) or urine (> 0.2 g excreted in a 24-hour collection sample).
Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour urine collection; all patients with >= 2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein
Patients must have a documented diagnosis of multiple myeloma with evidence of measurable disease i.e. serum M protein superior or equal to 0.5 g per dL measured using serum protein immunoelectrophoresis and or urine M protein superior or equal to 200 mg per 24 hours measured using urine protein immunoelectrophoresis.
Patients with urine dipstick for proteinuria > 2+; patients with >= 2+ proteinuria on baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate =< 1 g of protein in the 24-hour urine; alternatively, proteinuria testing can be performed according to local standards
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 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)
Persistent proteinuria ? Grade 3 NCI-CTCAE v4.03 (> 3.5 g/24 hrs, measured by urine protein: creatinine ratio on a random urine sample).
Measureable 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).
Urine protein/creatinine (UPC) ratio < 1.0 within 14 days prior to registration; if the UPC ratio is >= 1.0 then the patients should undergo a 24-hour urine collection and must demonstrate =< 1g of protein in 24 hours to be eligible)
Proteinuria at screening demonstrated by urine analysis (UA) > 1+ and 24 hour urine protein >= 1 gram/24 hours
Subjects having greater than 1+ proteinuria on urine dipstick testing will undergo a 24-hour urine collection for quantitative assessment of proteinuria. Subjects with a urine protein greater than or equal to 1 g/24 hours will be ineligible.
Urine protein/creatinine ratio (UPCR) =< 2
Patients 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
Urine protein:creatinine ratio =< 1.0 at screening
Urine protein (albumin)/creatinine ratio of < 1.0
Participant's urinary protein is ? 1+ on dipstick or routine urinalysis (UA); if urine protein ? 2+, a 24-hour urine collection must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study
Urine protein must be screened by urinalysis; if protein is 2+ or higher, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment
Grade 2 or higher proteinuria (2+ or higher protein on urinalysis or urine protein:creatinine (UPC) ratio >= 1.0; if both tests are performed, UPC should be used to evaluate eligibility) or hematuria
Known proteinuria defined by >= 2+ protein by urinalysis (UA) or >= 1 gram protein by 24 hour urine collection; Note: Subjects that are >= 2+ or greater on dipstick but < 1 g protein on 24 hour urine ARE eligible to participate
Urinalysis =< 1+ protein
Urine protein =< 1+ on urine dipstick (if 2+ seen on first test, re-test at least 24 hours later), within 14 days of study registration
Clinically significant proteinuria: \r\n* Subjects having > 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria; subjects with urine protein >= 1 g/24-hour will be ineligible
Serum myeloma protein (M-protein) >= 3 g/dl and/or bone marrow plasma cells >= 10 %
Within the past 4 weeks: Serum monoclonal protein >= 1.0 g/dl
Within the past 4 weeks: Urine monoclonal protein > 200 mg/24 hour
Within the past 4 weeks: Serum immunoglobulin free light chain > 10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)
Urinary protein is <2+ on dipstick or routine urinalysis.
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
Serum M-protein ? 0.5 g/dL
Urine M-protein ? 200 mg/24 hours
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
Urine protein-to-creatinine (UPC) ratio =< 2 mg/mg or 24-hour urine protein < 2 g
Persistent proteinuria >= grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample)
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
Proteinuria less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than week apart, or a urine protein:creatinine (UPC) ration of =< 1
Has greater than 1+ proteinuria on a urine dipstick or equivalent routine laboratory analysis will require further testing with a urine protein to creatinine ratio (UPCR); if the UPCR >= 1, then the patient will not be eligible for study entry; however, if urinalysis or equivalent routine laboratory analysis shows no protein, then UPCR testing is not required
The urine protein: creatinine ratio (UPCR) is derived as follows: protein concentration (mg/dL)/creatinine (mg/dL); patients must have a UPCR < 1.0 to allow participation in the study
Urinary protein =< 1+ obtained =<14 days prior to randomization\r\n* Patients discovered to have >= 2+ proteinuria must have a spot urine protein:creatinine ratio (UPCR) < 1.0
Measurable 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 abnormal
Measurable 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)
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 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 cells
Persistent proteinuria grade 2 or higher measured by urine protein:creatinine ratio on a urine sample or during 24-hour assessment
Urine dipstick for proteinuria < 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1g of protein in 24 hours to be eligible)
Urinary protein =< 2+ by urine analysis; if urine protein is > 2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is < 2 g per 24 hours
Urine protein creatinine (UPC) ratio must be < 1.0 gm
If UPCR ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended
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
Persistent proteinuria >= grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hours [hrs], measured by urine protein:creatinine ratio on a random urine sample)
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)
Urine protein/creatinine ratio (UPCR) =< 2
Measurable 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 aspiration
Serum M-protein ? 500 mg/dL
Urine M-protein ? 200 mg/24 h
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
Participants 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 ratio
Urine protein to creatinine ratio (UPC) < 1 (tested within 14 days prior to registration)\r\n* If UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
24-hour urine protein, if required < 1 g (tested within 14 days prior to registration)\r\n* If UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
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
Palliative radiation that does not include a target lesion is allowed. Subjects having a spot urine protein:creatinine ratio of > 1 will undergo 24-hour collection for quantitative assessment of proteinuria. If urine protein > 1 gram/24 hours, the subject will be ineligible
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
Newly 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 ratio
Measurable 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 radiated
Relapsed and/or refractory multiple myeloma with measurable disease, as defined by one or both of the following (assessed within 14 days prior to initiation of therapy): a) serum myeloma protein (M-protein) >= 0.5 g/d; b) urine Bence-Jones protein >= 200 mg/24 hours
Patients with light chain only myeloma are eligible; the involved free light chain level >= 100 mg/L with abnormal serum free light chain ratio
Urine protein to creatinine ratio of < 1 prior to registration
Patients must not have baseline proteinuria within 14 days prior to registration as demonstrated by either:\r\n* Urine protein: creatinine (UPC) ratio < 1.0 at screening, OR\r\n* Urine dipstick for proteinuria =< 2+; NOTE: patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible
Proteinuria < 3 + by urinalysis or urine dipstick
Subjects having greater than 1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein greater than or equal to 1 g/24-hour will be ineligible.
Measurable 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 therapy
Urine protein to creatinine ratio < 1, or, 24-hour urine protein < 1 g; if urine protein to creatinine (UPC) >= 1, then a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
Urine protein: creatinine ratio > 1
Urine protein to creatinine ratio (UPC) < 1\r\n* Or, 24-hour urine protein < 1 g\r\n* If UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
Urine protein =< 1+ on dipstick or routine urinalysis; if urine dipstick or routine urinalysis indicates proteinuria >= 2+, then a 24-hour urine must be collected and must demonstrate < 100 mg of protein in 24 hours
Measurable 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 acceptable
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
Measurable 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.
Urine protein =< 1+ OR urine protein to creatinine (UPC) ratio =< 1; if UPC ratio is > 1 on urinalysis, then 24-hour urine collection for protein must be obtained and level must be < 1,000 mg for patient enrollment
Urine protein should be screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment; NOTE: UPC ratio of spot urine is an estimation of the 24-urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
Measurable 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/uL
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
Urine protein: creatinine (UPC) ratio < 1.0 within 14 days prior to registration OR urine dipstick for proteinuria =< 2 positive (+) (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is < 1.0 to be eligible; if the UPC ratio is >= 1.0 then the patients should undergo a 24-hour urine collection and must demonstrate =< 1g of protein in 24 hours to be eligible)\r\n* Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
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
Urine protein to creatinine ratio (UPC) < 1; if UPC >= 1, then a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < 1 g to be eligible
Urine protein/urine creatinine ratio (UPCR) =< 1
Urinary protein =< 100 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 h urine sample
Urinalysis urine protein:creatinine ratio (UPCR) < 1 or < 1000 mg protein/24 hour (hr)
Urine dipstick for proteinuria < 2+; patients with < 2+ proteinuria on baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate =< 1 g of protein in the 24-hour urine; alternatively, proteinuria testing can be performed according to local standards
Urine Protein Creatinine (UPC) ratio < 1.0 or 24 hour urine protein ratio < 1000 mg
Urine protein/creatinine ratio (UPCR) =< 1
Urine protein to creatinine ratio < 1; or, 24-hour urine protein < 1 g; if urine protein creatinine ratio (UPC) >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
Urine protein/creatinine ratio (UPCR) =< 1
Serum M-protein ? 1 g/dL (? 10 g/L).
Urine M-protein ? 200 mg/24 hours.
Urine protein to creatinine ratio (UPC) < 1; if UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
Urine dipstick proteinuria < 2+ or urine protein/creatinine (UPC) ratio =< 1.0 obtained =< 14 days prior to randomization\r\n* Note: patients discovered to have >= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate =< 1 g of protein in 24 hours
Proteinuria: patients are allowed to have 0, trace, or 1+ protein by urine dipstick or urinalysis to enroll, if >= 2+ must check 24 hour (h) urine protein and must be < 1g to start study
Urine protein to creatinine ratio (UPCR): < 1.0
Urinary protein < 2+ (unless total quantitative protein is < 500 mg protein/day as determined by 24 hour [H] urine collection)
Patients with proteinuria > 1+ on urine dipstick or urine protein creatinine (UPC) ratio >= 1 at screening; if > 1+ proteinuria is detected on surveillance, a 24-hour collection must be performed if eligibility is desired; patients with a 24-hour urine protein content of =< 500 mg are eligible
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)
Within 14 days prior to registration: Urine protein/creatinine ratio should be =< 1
Quantitative urine protein by dipstick =< 100
Urine protein to creatinine ratio (UPC) =< 1; a UPC is required only if the urine protein is > 100; if UPC >1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
Urine protein:creatinine ratio of < 1
Serum M-protein ? 0.5 g/dL
Urine M-protein ? 200 mg/24 hours
Subjects with a urine protein/creatinine ratio greater than 1
Urine protein to creatinine ratio (UPC) < 1
Measurable 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
Urine protein to creatinine (UPC) ratio of < 1 assessed in a random or spot urine sample; if UPC >= 1, then a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < 1 gram to be eligible
Patients with proteinuria on screening urinalysis confirmed to be > 1 g/24 hr by 24 hour urine collection
Proteinuria as demonstrated by a urine protein: creatinine (UPC) ratio >= 1.0 at screening
Serum creatinine =< 1.5 x ULN or calculated creatinine clearance (CrCl) >= 40 cc/min and random urine protein:creatinine ratio (UPC) < 1 or 24-hour (hr) urine protein < 1 g, within 14 days of registration
Serum monoclonal protein >0.5g/dL and/or 0.2g/24hr urine light chain excretion
Measurable 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
Urine protein to creatinine ratio (UPC) < 1 (note, if >= 1, then a 24-hour urine protein must be assessed: if 24-hour urine protein > 1 g, patient ineligible)
Patients with greater than 1+ proteinuria on a urine dipstick or equivalent routine laboratory analysis will require further testing with a urine protein to creatinine ratio (UPCR); UPCR must be calculated as follows: UPCR = protein concentration (mg/dL)/creatinine (mg/dL); if the UPCR >= 1 then the patient will not be eligible for study entry; however, if urinalysis or equivalent routine laboratory analysis shows no protein, then UPC testing is not required
Urinary protein < 2+ by urine dipstick; if dipstick is >= 2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is < 2 g per 24 hours
Spot urine must not show 1+ or more protein in urine or the patient will require a repeat urinalysis; if repeat urinalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion < 1000 mg/24 hours
Patients must have a 24 hour (hr) urine collection showing less than 2000 mg of protein; EXCEPTION: patients with hematuria will be eligible with up to 3000 mg protein per 24 hours provided they do not have casts, eosinophiluria or electrolyte wasting
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
Urine protein: creatinine ratio greater than or equal to 1.0
Urine protein to urine creatinine ratio (UPC) < 1.0; if UPC >= 1 then a 24 hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
EXPANSION COHORT ONLY: Urine protein to urine creatinine ratio (UPC) < 1.0; if UPC >= 1 then a 24 hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
Total protein > 6.4
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%
Urine protein: creatinine ratio >= 1.0 at screening
Spot urine must not show 1+ or more protein in urine or the subject will require a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion <1,000 mg per 24 hours.
Newly 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 ratio
Measurable 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 plasmacytomas
Participants with urine protein ?1 gram/24 hour
Less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than 1 week apart, OR < 1 gm protein on 24-hour urine collection or a urine protein: creatinine ratio of < 1
Patients with clinically significant proteinuria at screening as demonstrated by urine protein:creatinine (UPCR) ratio >/= 1.0 at screening. The UPCR has been found to correlate directly with the amount of protein excreted in a 24 hour urine collection. Specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24 hour urine collection. Obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24 hour urine). Send sample to lab with request for urine protein and creatinine levels [separate requests].
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
Urine protein < 1+; if >= 1+, 24 hour urine protein should be obtained and should be < 1000 mg
Significant proteinuria: urinary protein/creatinine ratio >0.5 mg/mg in a non first void urine sample
Either urine protein < 1+ or measured 24 hour urine protein < 500 milligram
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
Continued from Inclusion #8: Serum creatinine </= 1.5 ULN or creatinine clearance (CrCl) >/= 45 mL/min (CrCl = Wt (kg) x (140-age)/72 x Cr level, female x 0.85) for pts w/ creatinine levels above institutional normal; Amylase & lipase < 1.5 x the ULN; Urinalysis (UA) must show less than 1+ protein in urine, or the pt will require a repeat UA. If repeat UA shows 1+ protein or more, a 24 hour urine collection will be required & must show total protein </= 1000 mg/24 hour to be eligible
Measurable disease M component in serum (? 0.5 g/dL) and/or urine (? 0.2 g excreted in a 24 hour collection sample)
Non-Measurable M Protein (serum or urine) and measurable sFLC (< 100 mg/mL)
Persistent proteinuria ? Grade 3 NCI CTCAE v4.0 as defined as > 3.5 g/24 hours, measured by urine protein: creatinine ratio on a random urine sample.
mGPS of 1: C-reactive protein >10 mg/L and albumin ?35 g/L
mGPS of 2: C-reactive protein >10 mg/L and albumin <35 g/L
Proteinuria =< grade 1+ or 24-hour protein =< 1000 mg for patients with proteinuria above 1+ or urine protein to creatinine ratio < 1.0
Patient’s with a history of kidney disease or persistent proteinuria must have < grade 3 proteinuria per NCI CTCAE v4.0 at screening; if a patient has a history of kidney disease or persistent proteinuria, a urine protein test will be performed on a random urine sample; if the result is normal then no additional testing is required; if the result is abnormal, a 24 hour urine will be collected to determine if proteinuria is < grade 3
Patient’s with a history of kidney disease or persistent proteinuria must have < grade 3 proteinuria per NCI CTCAE v4.0 at screening; if a patient has a history of kidney disease or persistent proteinuria, a urine protein test will be performed on a random urine sample; if the result is normal then no additional testing is required; if the result is abnormal, a 24 hour urine will be collected to determine if proteinuria is < grade 3
Serum M-protein ? 0.5g/dL of IgA or ? 1 g/dL of IgG, or
Urine M-protein ? 200 mg/24 hr, or
Patient’s with a history of kidney disease or persistent proteinuria must have < grade 3 proteinuria per NCI CTCAE v 4.0 at screening; if a patient has a history of kidney disease or persistent proteinuria, a urine protein test will be performed on a random urine sample; if the result is normal then no additional testing is required; if the result is abnormal, a 24 hour urine will be collected to determine if proteinuria is < grade 3
Urine protein/creatinine < 1 mg/mg
Urine protein < 1+; if >= 1+, 24 hour urine protein should be obtained and should be < 1000 mg
C-reactive protein >10 mg/L AND albumin ?35 g/L; Score = 1
C-reactive protein >10 mg L AND albumin <35 g/L; Score = 2
Proteinuria at Screening. Subjects with a urine dipstick protein ? 2+ at Screening will undergo a 24-hour urine collection and must demonstrate ? 1g of protein in 24 hours to be eligible.
Urine protein/creatinine (UPC) ratio =< 1.0 unless the patient has a neobladder
Serum M-protein ? 0.5 g/dl (? 5 g/l)
Urine M-protein ? 200 mg/24 h
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)
If the serum protein electrophoresis is unreliable for routine M-protein measurement, quantitative immunoglobulin levels on nephrolometry or turbidometry will be followed.
Urine dipstick for proteinuria of =< less than 1+; if urine dipstick is > 1+ then a 24 hour urine for protein must demonstrate < 500 mg of protein in 24 hours to allow participation in the study
UPC ratio < 1.0 at screening or 24 hours urine protein < 1 gm (Appendix D)
Proteinuria as defined as >= 2+ on urine dipstick; if dipstick urinalysis shows >= 2+ proteinuria, 24-hour urine for protein must be < 2 grams
Urine protein/creatinine ratio (UPCR) =< 2
Urine protein < 1+; or if >= 1+ then 24 hour urine protein should be obtained and should be < 1000 mg
Serum monoclonal protein ?1 g by protein electrophoresis
Urine monoclonal protein >200 mg on 24 hour electrophoresis
Serum immunoglobulin free light chain ?10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
Must 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 abnormal
Routine urinalysis showing ?1+ protein or protein/creatinine ratio <0.5. For proteinuria ?2+ or urine protein/creatinine ratio ?0.5, 24-hour urine must be collected and the level must be <1 gram of protein in 24 hours for subject enrollment.
Urine protein/creatinine ratio (UPCR) =< 1
Proteinuria at screening as demonstrated by urine dipstick >= 2+
Serum M-protein ? 0.5 g/dL
Urine M-protein ? 200 mg/24 hours OR
Urine protein:creatinine ratio =< 1.0 OR 24-hour urine protein =< 500 mg (24-hour total urine protein only need be obtained if urine protein:creatinine ratio < 1.0)
Urine protein-creatinine ratio (UPCR) > 1 urinalysis or total urine protein > 500 mg/24 hours (h)
A monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of ? 1.0 g/dL.
Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ? 200 mg/24 hours.
Involved serum free light chain (FLC) level ? 10 mg/dL, provided the serum FLC ratio is abnormal.
Less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than 1 week apart, or < 1 gm protein on 24-hour urine collection or a urine protein:creatinine ratio of < 1
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 %
Serum M-protein ? 0.5 g/dL, or
Urine M-protein ? 200 mg/24 hours, or
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)
Measurable 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)
Kidney: albuminuria ? 500 mg/day in a 24-hour urine specimen
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
Measurable 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)
Serum M-protein ? 1.0 g/dL
Urine Bence Jones protein ? 200 mg/24 hr
Patients 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 cells
Urine protein creatinine (UPC) ratio < 1; note: urine protein must be screened by urine analysis for UPC ratio; for UPC ratio >= 1.0, 24-hour urine protein must be obtained and the level should be < 1,000 mg for registration
Measurable 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
Have persistent 2+ protein by urinalysis (patients with 2+ proteinuria that have a spot protein:creatinine ratio of less than 0.3 may be enrolled) or a history of nephrotic syndrome.
If baseline urine protein creatinine (UPC) >= 1, a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < grade 3 (> 3.5 g/24 hours) to be eligible
Urine protein/creatinine ratio (UPCR) =< 1
Urine protein/creatinine ratio (UPCR) =< 1 mg/mg (113.2 mg/mmol) creatinine or 24-hour (hr) urine protein of < 1 g
Greater than 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart or 24-hour urine protein of > 1 g; patients with < 2+ proteinuria are eligible following initial determination by urinalysis within 1 week prior to enrollment and do not need the urinalysis repeated
Patient has proteinuria as demonstrated by urine protein:creatinine ratio ? 1.0 at screening or urine dipstick for proteinuria ? 2 (patients discovered to have ? 2 proteinuria on dipstick at baseline should undergo a 24-hour urine collection and must demonstrate < 2 g of protein in 24 hours to be eligible).
Serum M-protein ? 0.5 g/dL, or
Urine M-protein ? 200 mg/24 hour, or
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
Urinary protein =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 h urine sample
Patients 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)
Urine for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible)
Proteinuria, as demonstrated by a 24-hour protein of >= 2000 mg; urine protein will be screened by urine protein-creatinine ratio (UPC); for UPC ratio > 1.0, a 24-hour urine protein will need to be obtained and the level should be < 2000 mg for patient enrollment
Urine protein should be screened by urinalysis for urine protein creatinine ratio (UPCR); for UPCR > 1, a 24-hour urine protein should be obtained and the level should be < 500 mg
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%
Has urinary protein is ? 1+ on dipstick or routine urinalysis; if urine protein ? 2+, a 24-hour urine collection must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
Urine M ?200 mg per 24hr
Urine M protein ?200 mg per 24hr
Urine M protein ?200 mg per 24hr
Patients with clinically significant proteinuria; urine protein should be screened by urine protein-creatinine ratio (UPCR); patients must have a UPCR < 1.0 to allow participation in the study
Urine protein to creatinine (UPC) ratio < 1; if UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
Serum M-protein ? 0.5 g/dL
Urine Bence-Jones protein ? 200 mg/24 hours
Proteinuria as defined by positive urine dipstick for protein OR urine protein/creatinine (UPC) ratio >= 1.0; if these criteria are not met, the patient must have a 24 hour urine collection that demonstrates < 1 gm protein over 24 hours
If there is proteinuria present on dipstick, patients are excluded if they have > 500 mg protein on 24 hour urine collection
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.
Monoclonal protein present in the serum and/or urine
IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ? 1.0 g/dl or urine M-protein level ? 200 mg/24 hours
IgA multiple myeloma: Serum M-protein level ? 0.5 g/dl or urine M-protein level ? 200 mg/24 hours
IgM 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/24hours
IgD multiple myeloma: Serum M-protein level ? 0.05 g/dl or urine M-protein level ? 200 mg/24 hours
Light 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:
Measurable 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)
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
Proteinuria > 1+ on urine dipstick testing or 30 mg/dL
Serum M-protein ? 1.0 g/dL by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative IgA; or
Urinary M-protein excretion at least 200 mg/24 hours; or
If serum protein electrophoresis is felt to be unreliable for routine M- protein measurement, then quantitative Ig levels by nephelometry or turbidometry are acceptable.
MM 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).
Creatinine less than or equal to 1.5 x ULN; if urine protein to creatinine ratio is greater than or equal to 1, a 24 hour urine protein must be assessed; subjects must have a 24 hour urine protein value less than 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
Urine to protein to creatinine (UPC) ratio < 1; if UPC > 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
Urine protein: urine protein:creatinine (UPC) ratio 1.0 OR urine dipstick for proteinuria: urine dipstick for proteinuria > 2+; patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible
Urine protein to creatinine (UPC) ratio < 0.5 or if >= 0.5, 24-hour urine protein must be < 1000 mg
Participants having >1+ proteinuria on urine dipstick testing will undergo 24 hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ?1 grams (g)/24 hours will be ineligible.
Urine protein: creatinine (UPC) ratio < 1.0 within 14 days prior to registration OR urine dipstick for proteinuria ? 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is <1.0 to be eligible. If the UPC ratio is ? 1.0 then the patients should undergo a 24-hour urine collection and must demonstrate ? 1g of protein in 24 hours to be eligible). *Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using one of the following formulas:
[urine protein]/[urine creatinine]: if both protein and creatinine are reported in mg/dL
[(urine protein) x0.088]/[urine creatinine]: if urine creatinine is reported in mmol/L
Proteinuria, as demonstrated by > 1.5 gram of protein in a 24-hour urine collection; all patients with >= 2+ protein on dipstick urinalysis at baseline must undergo 24-hour urine collection for protein
Subjects must have a C-reactive protein (CRP) > 3 mg/L
Proteinuria as demonstrated by a urine protein creatinine (UPC) ratio >= 1.0 at screening
Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour urine collection
Urinary protein is ?1+ on dipstick or routine urinalysis or 24-hour urine demonstrating <1 gram of protein.
Participants 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 disorder
Monoclonal protein present in the serum and/or urine
MM\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 criteria
Have detectable disease measured by a specific protein in your blood and/or urine
Diagnosis 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 ratio
Total protein within 2 x ULN
Participants must have a 24-hour calcium concentration that is =< 300 mg/24 hours as measured by 24-hour urine collection at baseline
- Proteinuria < 1 g/24 hours based upon 24 hour urine collection or spot urine protein/creatinine ratio
Urine protein to creatinine ratio (UPC) < 1 (evaluated within 28 days of randomization); if UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1g to be eligible
Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 1, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment; Note: UPC ratio of spot urine is an estimation of the 24 hour urine protein excretion- a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
Serum 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; or
Urinary M-protein excretion at least 200 mg/24 hours; or
Serum free light chain (FLC) ? 100 mg/L, provided that the serum FLC ratio is abnormal.
Patients unwilling or unable to comply with the protocol, including providing 24-hour urine samples for urine protein electrophoresis at the required time points.
Urine protein =< 1+ on urine dipstick (if 2+ seen on first test, re-test at least 24 hours later) (within 14 days of study registration)
Measurable 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 ratio
- Proteinuria < 1 g/24 hours based upon 24 hour urine collection or spot urine protein/creatinine ratio
C-reactive protein > 3 mg/L
Serum M-protein >=500 mg/dL (>=5 gram per liter [g/L]).
Urine M-protein >=200 mg/24 hours.
In 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.
Evaluable disease (serum protein electrophoresis [SPEP]/urine protein electrophoresis [UPEP]/serum free light chain [SFLC] criteria)
Measurable 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 leukemia
Participants having >1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ?1 g/24 h will be ineligible.
Known protein C, protein S, or anti-thrombin deficiency or other known thrombophilic disorders