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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 |
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A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or urine) |
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Measurable disease defined as |
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M-spike ≥ 500mg/dL, or ii. Urine protein M-spike of ≥ 200 mg/day, or iii. Serum free light chains ≥ 10 mg/dL, and an abnormal κ:λ ratio |
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Relapsed MM is defined as previously treated MM that progresses and requires initiation of salvage therapy but does not meet the criteria for refractory MM |
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ii. Refractory MM is defined as disease that is nonresponsive (failure to |
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Participants in Part 1 should have failed all other available options including having had ≥ 3 prior lines of therapy including a proteasome inhibitor, IMiD agent, and an anti-CD38 monoclonal antibody |
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Participants in Part 2 should have had and failed ≥ 1 but ≤ 7 prior lines of therapy and will have had prior treatment with both a proteasome inhibitor and an IMiD agent |
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Note: A line of therapy consists of greater ≥ 1 complete cycle of a single |
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Participant has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of therapy |
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agent, a regimen consisting of combination of several drugs, or a planned |
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sequential therapy of various regimens. Induction therapy with consolidation |
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and maintenance following stem cell transplant is considered a single line of |
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therapy |
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Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory and not have had carfilzomib within the past 6 months |
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achieve minimal response or development of progressive disease) while on |
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primary or salvage therapy or progresses within 60 days of last therapy |
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Positivity for t(11;14) by validated fluorescence in situ hybridization (FISH) testing |
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assay in a pre-defined laboratory |
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fresh bone marrow aspirate sample must be collected at screening and sent to central laboratory for t(11;14) FISH testing |
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Adequate organ function defined as |
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Hemoglobin ≥ 8.0 g/dL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions |
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Platelet count ≥ 75,000/μL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions |
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Absolute neutrophil count (ANC) ≥ 1000/mm3 [ANC = (% of segmented neutrophils + % of segmented bands) x total WBC count within 7 days before first dose of study treatment |
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ALT and AST ≤ 3 x upper limit of normal (ULN) and total bilirubin ≤ 2.0 x ULN Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 45 mL/min/1.73 m2 calculated by the MDRD-6 formula |
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Non secretory MM (Serum free light chains < 10 mg/dL)
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Solitary plasmacytoma
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Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or > 2.0 x 109/L circulating plasma cells by standard differential)
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Waldenström macroglobulinemia
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Amyloidosis
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Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome
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Uncontrolled diabetes (HbA1c > 7% or 53 mmol/mol or requiring insulin at study entry
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Chronic respiratory disease that requires continuous oxygen
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Participant has any of the following conditions
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Myocardial infarction ≤ 6 months before screening
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Significant cardiovascular disease, including but not limited to
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Ejection fraction ≤ 50%
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Unstable angina≤ 3 months before screening
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New York Heart Association Class III or IV congestive heart failure
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History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
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Heart rate-corrected QT interval > 480 milliseconds based on Fridericia's formula
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History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
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Uncontrolled hypertension at screening, defined as systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg by ≥ 2 consecutive measurements
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Known infection with human immunodeficiency virus (HIV)
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Serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows
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Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Participants with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable (limitation of sensitivity < 20 IU/mL) ,), and if they are willing to undergo monthly monitoring for HBV reactivation
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Presence of HCV antibody. Participants with presence of HCV antibody are eligible if HCV RNA is undetectable (limitation of sensitivity < 15 IU/mL)
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Note: Other protocol defined Inclusion/Exclusion criteria may apply
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