{"analyses":[{"ciNumSides":"TWO_SIDED","groupIds":["OG000","OG001","OG002","OG003"],"nonInferiorityType":"OTHER","paramType":"Maximum Tolerated Dose (mg/m²)","paramValue":"70"}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"},{"groupId":"OG003","value":"2"}]}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"15"},{"groupId":"OG003","value":"6"}],"units":"Participants"}],"description":"The MTD was defined as the highest carfilzomib dose at which \\< 33% of participants had a treatment-related DLT during the first 28-day cycle. A DLT was categorized as nonhematologic or hematologic and defined as follows:\n\nNonhematologic:\n\n* ≥ grade 3 nonhematological toxicity (excluding nausea, vomiting, diarrhea, fatigue lasting \\< 14 days, increased serum creatinine or electrolyte abnormalities not clinically significant or requiring treatment)\n* ≥ grade 3 acute kidney injury (creatinine \\> 3 x baseline or \\> 4.0 mg/dL) lasting \\> 72 hours\n* ≥ grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy\n\nHematologic:\n\n* grade 4 neutropenia (absolute neutrophil count \\[ANC\\] \\< 500/mm³) for \\> 7 days\n* febrile neutropenia (ANC \\< 1000/mm³ with a fever ≥ 38.3ºC) of any duration\n* grade 4 thrombocytopenia (\\< 25 000/mm³) for \\> 14 days, despite holding treatment\n* grade 3 or 4 thrombocytopenia (\\< lower limit of normal) associated with \\> grade 1 bleeding","groups":[{"description":"Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.","id":"OG000","title":"Phase 1 Carfilzomib 45 mg/m²"},{"description":"Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.","id":"OG001","title":"Phase 1: Carfilzomib 56 mg/m²"},{"description":"Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.","id":"OG002","title":"Phase 1: Carfilzomib 70 mg/m²"},{"description":"Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.","id":"OG003","title":"Phase 1: Carfilzomib 88 mg/m²"}],"paramType":"NUMBER","populationDescription":"Participants in phase 1 who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).","reportingStatus":"POSTED","timeFrame":"28 days","title":"Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)","type":"PRIMARY","unitOfMeasure":"participants"}