Multiple myeloma
Conditions
Interventions
investigational material(s)
Generic name etc : Ixazomib (MLN9708)
INN of investigational material : Ixazomib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Invest
Sponsors
Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Japanese participants with multiple myeloma according to diagnostic criteria. 2) Previously treated with 2 or more regimens including all the following drugs; bortezomib, thalidomide or lenalidomide, corticosteroids 3) participants who have relapsed following the previous therapy or failed to continue the treatment due to their intolerability to the last treatment regimen for myeloma 4) Measurable disease defined by at least one of the following 3 measurements; Serum M-protein: >= 1 g/dL (>= 10 g/L), Urine M-protein: >= 200 mg/24 hours, Serum free light chain (FLC) assay: involved FLC level >= 10 mg/dL (>= 100 mg/L), provided that the serum FLC ratio is abnormal. 5) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 6) participants 20 years or older at giving their informed consent. 7) participants must be able to stay in the hospital for Cycle 1 treatment. 8) Participants must meet the following laboratory criteria at screening; Absolute neutrophil count (ANC): >= 1,000/mm^3, Platelet count: >= 75,000/mm^3, Total bilirubin: = 30 mL/min; MLN9708 with Rd cohort: >= 60 mL/minA 9) participants recovered (Grade 1) from the toxicities of the prior treatments. ANC >= 1,000/mm^3. 10) Life expectancy of at least 3 months, in the judgment of the investigator. 11) participants conforming to proper management guidelines of lenalidomide (MLN9708 with Rd cohort only).
Exclusion criteria
Exclusion criteria: 1) Participants with plasmacytoma only. 2) Participants with plasma cell leukemia. 3) Participants with central nervous system invasion. 4) Radiotherapy within 14 days before enrollment. 5) Other anti-tumor drug administration within 21 days before enrollment. 6) Other investigational products administration within 21 days before enrollment (60 days from the last dose for carfilzomib). 7) Antibody treatment within 42 days before enrollment. 8) Systemic treatment with potent CYP1A2 inhibitors (fluvoxamine, enoxacin), potent CYP3A inhibitors (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole), or potent CYP3A inducers (rifampin, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of foods containing Ginkgo biloba extract, St. John's Wort, or grapefruit within 14 days before enrollment. 9) Treatment with corticosteroids greater than 10 mg of prednisolone per day. Inhaled and topical steroids are permitted. 10) Peripheral neuropathy >= Grade 2 11) Diarrhea >= Grade 2 12) Major surgery requiring general anesthesia within 14 days before enrollment 13) Infection requiring systemic antibiotic treatment or other serious infections within 14 days before enrollment 14) Evidence of concurrent uncontrolled cardiovascular conditions including hypertension, cardiac arrhythmias, New York Heart Association (NYHA) Class III or worse congestive heart failure, angina, myocardial infarction, or cerebral infarction within 6 months before enrollment. 15) QTc > 470 milliseconds on a 12-lead ECG obtained during the screening period 16) Tested positive for human immunodeficiency virus (HIV) antibody, hepatitis B virus surface antigen (HBs antigen), or hepatitis C virus (HCV) antibody during the screening period 17) Hypersensitivity to MLN9708 (including excipients), boron, or boron-containing drugs 18) Hypersensitivity to lenalidomide, or dexamethasone, or excipients contained in the formulation of each drug (MLN9708 with Rd cohort only) 19) Known gastrointestinal diseases (difficulty swallowing, inflamed gastroenteritis, and Crohn disease), or gastrointestinal procedure (endoscopic procedure is permitted), that could interfere with the oral absorption or tolerance of the study treatment 20) Uncontrolled diabetes mellitus 21) A history of interstitial lung disease or lung fibrosis, or a current complication of interstitial lung disease or lung fibrosis diagnosed by chest imaging. 22) Prior or current complications of deep vein thrombosis or pulmonary embolism (MLN9708 with Rd cohort only) 23) Diagnosed or treated for another malignancy within 2 years before the first dose of MLN9708 or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have complete resection. 24) Participants who do not consent to use adequate contraceptive precautions (e.g. condoms and oral contraceptives) during the following term: - For women with childbearing potential, from when giving their consent through 3 months after the last dose of MLN9708, dexamethasone, or lenalidomide - For men having their partners with childbearing potential, from when giving their consent through 4 months after the last dose of MLN9708, dexamethasone, or lenalidomide 25) Pregnant (e.g. positive for pregnancy test) or lactating. Lactation is prohibited from the first dose through 6 weeks after the last dose of MLN9708, dexamethasone, and lenalidom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Number of Participants who Experienced Dose Limiting Toxicities (DLTs) Time Frame: From Cycle 1 Day 1 until Cycle 2 Day 1 (Cycle length is equal to [=] 28 days) 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 (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. safety Number of Participants with 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) safety Number of Participants with Grade 3 or Higher TEAE related to Body Weight Time Frame: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days) 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). safety Number of Participants with Grade 3 or Higher TEAE related to Vital Signs Time Frame: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days) Vital signs were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local o | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Numbers of Participants Achieving Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR) 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 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 =) 90% decrease in serum M-protein with urine M-protein = 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 = 50% decrease in dFLC. A >=50% decrease in the size of soft tissue plasmacytomas present at baseline | — |
Countries
Japan
Outcome results
None listed