The purpose of this study is to characterize the single-dose pharmacokinetic (PK) parameters of ixazomib (MLN9708) in cancer participants with either normal renal function or severe renal impairment (RI), including participants with end-stage renal disease (ESRD).
The drug tested in this study was called ixazomib (MLN9708). Ixazomib was administered to participants with cancer and either normal renal function or severe renal impairment, including end-stage renal disease (ESRD) requiring hemodialysis. This study characterized the PK, safety and efficacy of ixazomib. The study enrolled 41 participants (37 multiple myeloma and 4 advanced solid tumor). The study was conducted in 2 parts, Part A and Part B. Participants were enrolled to receive: * Ixazomib 3.0 mg In Part A, all participants were asked to take one 3 mg ixazomib capsule, orally on Day 1. Participants who tolerated ixazomib in Part A had the option of continuing the study by participating in Part B. In Part B, participants received ixazomib (4, 3, or 2.3 mg per protocol) on Days 1, 8, and 15 of each 28-day cycle until participants experienced disease progression or unacceptable toxicity. This multicenter trial was conducted at 6 study sites in the United States and Canada. The overall time to participate in this study was 435 days. Participants made multiple scheduled visits to the clinic.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Ixazomib capsules
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States
Illinois Cancer Care
Peoria, Illinois, United States
University of Kansas Cancer Center, Clinical Research Center
Fairway, Kansas, United States
Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
Time frame: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Time frame: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Unbound AUClast: Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Time frame: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Number of Participants With Adverse Events
Adverse Event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: From signing of first dose of study drug up to the 30 days after the last dose of study drug (approximately up to 885 days)
Percentage of Participants With Overall Response (OR) in Relapsed/Refractory Multiple Myeloma (RRMM) Participants
Overall response rate defined as percentage of relapsed/refractory multiple myeloma participants who achieved partial response (PR), complete response (CR) and very good partial response (VGPR) according to International Myeloma Working Group Criteria. PR=\>50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or \<200 mg/24 h. If serum and urine M-protein are unmeasurable, \>50% decrease in difference between involved and uninvolved free light chain levels in place of M-protein criteria. If serum and urine M-protein and serum free light assay are not measurable, \>50% reduction in plasma cells in place of M-protein, provided baseline bone marrow plasma cell \>0%; CR=negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or \> 90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 h.
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University of Maryland
Baltimore, Maryland, United States
Mount Sinai Medical Center
New York, New York, United States
University of Oklahoma Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
Sarah Cannon Cancer Center
Nashville, Tennessee, United States
Mary Crowley Cancer Research Centers Medical City
Dallas, Texas, United States
Institute of Oncology Hematology Biomedical Research
Laredo, Texas, United States
University of Texas Health Science Center San Antonio
San Antonio, Texas, United States
...and 1 more locations
Time frame: Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days)
Duration of Response (DOR) in RRMM Participants
DOR was defined as time from date of first documentation of a PR or better to date of first documentation of progressive disease (PD) for responders. Increase of \>25% from lowest response value in any one or more of following: Serum M-component and/or (absolute increase must be \>0.5 g/dL); Urine M-component and/or (the absolute increase must be \>200 mg/24 h); difference between involved and uninvolved free light chain (FLC) levels and the absolute increase must be \> 10 mg/dL; Bone marrow plasma cell percentage; absolute percentage must be \> 5%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcaemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Responders without PD were censored at the date of the last response assessment that was stable disease (SD) or better.
Time frame: Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days)