The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics (PK) of ixazomib alone or in combination with lenalidomide and dexamethasone (Rd), and antitumor activity of ixazomib in participants with RRMM.
The drug being tested in this study is called ixazomib. This study will evaluate the tolerability, safety, and PK of ixazomib administered alone or in combination with lenalidomide and dexamethasone in participants with relapsed and/or refractory multiple myeloma. This study will enroll approximately 24 participants (3 to 6 participants in each dose-escalation cohort). Participants will be assigned to receive treatment in one of the four treatment cohorts: * Cohort 1: Ixazomib 4.0 mg * Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone * Cohort 3: Ixazomib 5.5 mg * Cohort 4: Ixazomib 5.5 mg + Lenalidomide and Dexamethasone This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately 7 years. Participants will make a final visit 29 days after receiving their last dose of drug for a follow-up assessment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Ixazomib capsules.
Lenalidomide capsules.
Dexamethasone tablets.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
DLT:Any following adverse events (AEs) possibly related to ixazomib assessed by Common Terminology Criteria for AEs (CTCAE) version 4.03; Grade 4 neutropenia/thrombocytopenia lasting \>7 consecutive days; Grade 3/greater neutropenia with fever/infections; Grade 3/greater thrombocytopenia with clinically significant bleeding; platelet count less than (\<)10,000 per cubic meter(/mm\^3); Grade 2 peripheral neuropathy with pain/Grade 3 or greater peripheral neuropathy; Grade 3/greater nonhematologic toxicities with exceptions of arthralgia/myalgia, fatigue lasting \<7 days manageable nausea/emesis with antiemetic prophylaxis, diarrhea that is controlled with supportive care; treatment delay of \>14 days at start of Cycle 2 due to failure of hematologic/nonhematologic recovery; Other Grade 2/greater ixazomib related nonhematologic toxicities required permanent discontinuation of ixazomib;Inability to receive at least 80% of planned lenalidomide doses due to the AEs related to ixazomib.
Time frame: From Cycle 1 Day 1 until Cycle 2 Day 1 (Cycle length is equal to [=] 28 days)
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
Time frame: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
Number of Participants With Grade 3 or Higher TEAE Related to Body Weight
Body weight abnormalities were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).
Time frame: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
Number of Participants With Grade 3 or Higher TEAE Related to Vital Signs
Vital signs were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).
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Time frame: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
Number of Participants With Grade 3 or Higher TEAE Related to 12-lead Electrocardiograms (ECGs)
12-lead ECGs were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).
Time frame: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Laboratory tests abnormalities were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).
Time frame: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
Cmax: Maximum Observed Plasma Concentration for Ixazomib
Time frame: Days 1 and 15 of Cycle 1: pre-dose and at multiple time points (15, 30, 60, and 90 minutes and 2, 4, 8, 24, 48, 96, and 168 hours) post-dose (Cycle length=28 days)
Number of Participants Who Achieved Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR)
Number of participants who achieved CR, PR, VGPR were assessed in accordance to International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and \<5% plasma cells in bone marrow. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC. VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or greater than or equal to (\>=) 90% decrease in serum M-protein with urine M-protein \<100 milligram per 24 hours (mg/24 hrs). If disease measurable only by SFLC, \>= 90% decrease in the difference between involved and uninvolved FLC levels (dFLC). PR: \>= 50% reduction of serum M-protein and \>= 90% reduction in urine M-protein or to \<200 mg/24 hrs, or a \>= 50% decrease in dFLC. A \>=50% decrease in the size of soft tissue plasmacytomas present at baseline
Time frame: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)