Relapsed and/or Refractory Multiple Myeloma
Conditions
Interventions
investigational material(s)
Generic name etc : Ixazomib, Bortezomib, Carfilzomib, Lenalidomide, Dexamethasone
INN of investigational material : Ixazomib, bortezomib, carfilzomib, lenalidomide, dexamet
Sponsors
Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligibility for Treatment Period I 1. Men and women of age 20 years or older at the time of enrollment. 2. Participants with RRMM. 3. Participants who are planned to start combination therapy with bortezomib, lenalidomide, and dexamethasone (VRd), or carfilzomib, lenalidomide, and dexamethasone (KRd) as second, third or fourth line of treatment. 4. Participants with measurable disease defined by one or more of the following three measurements. - Serum M-protein: >=0.5 g/dL (>= 5 g/L). - Urine M-protein: >= 200 mg/24 hours. - Serum free light chain assay: involved free light chain concentration >= 10 mg/dL (>= 100 mg/L) provided that the serum free light chain ratio is abnormal. 5. Participants with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 - 2; however, participants with ECOG PS 3 are eligible if they only have symptoms associated with bone lesions. 6. Participants who are considered by the principal investigator or investigator not to be eligible for transplant; or, if considered eligible for transplant, participants who are planned not to undergo transplant for at least 12 months after the start of the study treatment. 7. Participants must be registered with, and comply with, the guidelines of the lenalidomide management program. 8. Participants who, before implementing procedures related to clinical research (excluding standard medical practices), understand that they can withdraw consent at any time without suffering from disadvantages to future treatments, and can provide written informed consent. Eligibility for Treatment Period II 9. Participants must have received an injectable proteasome inhibitor (bortezomib or carfilzomib) in each treatment cycle of Treatment Period I.
Exclusion criteria
Exclusion criteria: Eligibility for Treatment Period I 1. Women who are nursing or pregnant. 2. Participants with another active malignancy, i.e. synchronous active malignancy or previous malignancy with a disease-free period of less than 5 years, except for participants with carcinoma in situ (intraepithelial carcinoma) or intramucosal carcinoma judged to be cured by topical treatment. 3. Participants with poorly controlled active thrombosis. 4. Participants who have participated in a clinical trial of ixazomib or have been treated with ixazomib. 5. Participants who were refractory to either treatment regimen based on lenalidomide and/or proteasome inhibitor(s). Note: Refractory MM is defined as PD on therapy or PD within 60 days after the last dose of a given therapy. Participants who have disease progressed 60 days after the last dose of a given therapy will be considered as relapsed in this study. 6. Participants with ongoing or active systemic infection, known hepatitis B virus infection, known hepatitis C virus infection, or known positivity to human immunodeficiency virus (HIV). 7. Participants who underwent major surgery within 14 days prior to enrollment to Treatment Period I. Surgery for bone lesions is not considered as major surgery. 8. Participants who received radiation therapy within 14 days prior to enrollment to Treatment Period I. If the radiation field is small, 7 days is considered as a sufficient interval between radiation therapy and chemotherapy. 9. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade >=2 peripheral neuropathy. 10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmia, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months before enrollment to Treatment Period I. 11. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment into Treatment Period I. 12. Participants with central nervous system involvement. 13. Inability to swallow oral medications, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal conditions that could interfere with the oral absorption or tolerance of treatment. 14. Psychiatric illness/social situation that would limit compliance with study requirements. 15. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. Eligibility for Treatment Period II 16. Participants who do not achieve at least a minimal response (MR) to VRd or KRd in Treatment Period I per the International Myeloma Working Group (IMWG) response criteria, 2014 revision. 17. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade >=2 peripheral neuropathy during Treatment Period I. 18. Participants with evidence of uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmia, symptomatic congestive heart failure, unstable angina, or myocardial infarction during Treatment Period I. 19. Participants using potent CYP3A4 inducing agents (rifampicin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or gingko biloba or St. John's wort. 20. Participants
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Progression-Free Survival (PFS) Rate at 12 Months from the Start of Study Treatment Timeframe; Up to 12 months PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase >=0.5 g/dl or urine M-component increase >=200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase >10 mg/dl or bone marrow plasma cell >=10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Overall Survival (OS) from the Start of Study Treatment Timeframe; Up to 39 months as a maximum OS is defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) is confirmed. Patients who are still alive will be censored at the last confirmed date of survival or the date of data cut-off, whichever is earlier. efficacy PFS from the Start of Study Treatment Timeframe; Up to 39 months as a maximum PFS is defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS will be assessed by IMWG Criteria. efficacy Percentage of Participants who Achieved VGPR or Better (CR + VGPR) Timeframe; Up to 39 months as a maximum VGPR or better (CR + VGPR) will be assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): >=50% reduction of serum M protein+reduction in 24-hour urinary M protein by >=90%/ to =50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ >=50% reduction in bone marrow plasma cells, if >=30% at baseline/ >=50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ >=90% reduction in serum M-protein+urine M-protein level =PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. efficacy Time to next treatment(TTNT) Timeframe; Up to 39 months as a maximum TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment. efficacy Duration of Therapy(DOT) Timeframe; Up to 39 months as a maximum DOT is defined as the treatment duration of study drug at study treatment Period I. efficacy Patient-Reported Outcome Health-Related Quality of Life (HRQoL) based on European Organization for Research and Treatment of Cancer (EORTC) | — |
Countries
Japan
Outcome results
None listed