A Study in Relapsed and/or Refractory Multiple Myeloma Patients Treated With Ixazomib Plus Lenalidomide and Dexamethasone

Study Overview
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Brief Summary
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The purpose of this study is to investigate the real world effectiveness and safety of ixazomib in combination with lenalidomide and dexamethasone (IRd) in patients with relapsed and/or refractory multiple myeloma (RRMM), under conditions of standard medical care. In addition, an exploratory study of biomarkers will be conducted.

Detailed Description
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The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have relapsed and/or refractory multiple myeloma (RRMM) under the conditions of standard medical care. This study is a non-interventional (observational), domestic, multicenter, prospective study in patients with RRMM. This study will look at the effectiveness and safety of ixazomib in combination with lenalidomide and dexamethasone in Japanese patients with RRMM as standard medical care. In addition, an exploratory study of biomarkers will be conducted in this study. The study will enroll approximately 300 patients. All participants will receive Ixazomib + Lenalidomide + Dexamethasone (IRd) therapy as standard medical care. This multi-center trial will be conducted in Japan. The overall time of observational period in this study will be 36 months. For each participant, the observation period will be from the start of IRd therapy until either 24 months after the enrollment date of the final patient to enroll, or until death or withdrawal of consent, whichever is earlier.

Official Title
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A Prospective, Multicenter, Observational Study in Relapsed and/or Refractory Multiple Myeloma Patients Treated With Ixazomib Plus Lenalidomide and Dexamethasone

Conditions
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Relapsed and/or Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Ixazomib
* Drug: Lenalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 20 years or older at the time of enrollment Patients with RRMM Participants who are scheduled to start IRd therapy Participants who can provide written informed consent of their own free will before the start of study treatment Participants who are judged by the principal investigator or investigator(s) to have the faculty to understand and comply with the requirements of the study Exclusion Criteria: Female Participants who are nursing or pregnant Participants who have been treated with ixazomib Participants with hypersensitivity to any of the components of IRd therapy, their analogs or excipients 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 Participants who are not registered with, or comply with, the guidelines of the lenalidomide management program Participants who, in the judgement of the principal investigator or investigator(s), are considered to be unsuitable for enrolment into the study

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ixazomib + Lenalidomide + Dexamethasone<br>Participants took ixazomib, lenalidomide, and dexamethasone under conditions of standard medical care in this study. The dosage and administration of ixazomib, lenalidomide, and dexamethasone were not defined by the protocol but according to the package insert of each drug. | Drug: Ixazomib<br>* Ixazomib capsules<br>Drug: Lenalidomide<br>* Lenalidomide capsules<br>Drug: Dexamethasone<br>* Dexamethasone tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as the period from the start of ixazomib, lenalidomide, dexamethasone (IRd) therapy in standard medical care to the time of confirmed progressive disease (PD) or confirmed death (regardless of the cause of death), whichever was earlier. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, 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. | Up to 36 Months as a maximum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS Rate at 12 Months and 24 Months After the Start of Treatment | PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months and 24 months after the date of start of study treatment. PFS was assessed by IMWG Criteria (2014 version). Per IMWG criteria, PD: serum M-component increase ≥ 0.5 g/dl or urine M-component increase ≥ 200 mg/24-hour/ difference between involved and uninvolved 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. | 12 months and 24 months | 
| Overall Survival (OS) | OS is defined as the period from the start of IRd therapy in standard medical care to the time when death (regardless of the cause of death) is confirmed. | Up to 36 months as a maximum | 
| Percentage of Participants Who Achieve or Maintain Any Best Response | Best response is defined as the cumulative numbers of participants who achieve each level of best response including partial response (PR), very good PR (VGPR) and complete response (CR) assessed with IMWG Criteria after each cycle of treatment. Per IMWG criteria, PR: ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥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: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine M-protein level <100 mg/24-hour. CR: negative immunofixation on serum+urine +disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. | Up to 36 months as a maximum | 
| Time to Next Treatment (TTNT) | TTNT will be measured as the period from the start of IRd therapy in standard medical care to the start of next treatment or time when death is confirmed (regardless of the cause of death), whichever is earlier. | Up to 36 months as a maximum | 
| Duration of Therapy (DOT) | DOT is defined as the treatment duration of IRd therapy. | Up to 36 months as a maximum | 
| Percentage of Participants Who Continue to Receive Treatment at 12 Months and 24 Months After Start of Treatment |  | 12 months and 24 months | 
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. | Up to 36 months as a maximum | 
| Percentage of Participants Who Achieve VGPR or Better (CR+VGPR) | The percentage of participants of CR + VGPR is defined as the rate of participants who achieve a best response of VGPR or better (sCR, CR, or VGPR) according to the IMWG Criteria after the start of the IRd therapy. | Up to 36 months as a maximum | 
| Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Global Health Status Score | EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores of Global Health Status in EORTC QLQ-C30 were linearly transformed to a total score between 0-100 and reported, with a high score indicating better QOL. | Baseline and End of Treatment (Up to 37 cycles, each cycle was of 28 days) | 
| Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future. For the body image scale, higher scores = better body image. Higher score for the disease symptoms scale = higher level of symptomatology. | Baseline and End of Treatment (Up to 37 cycles, each cycle was of 28 days) | 
| Rate of Minimal Residual Disease (MRD) Negativity in Bone Marrow in Participants Who Achieved CR | Rate of MRD will be calculated by the percentage of participants who are MRD-negative. | Up to 36 months as a maximum | 
| Relative Dose Intensity (RDI) | RDI is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment* number of prescribed doses per cycle* the number of treated cycles]. | Up to 36 months as a maximum | 
| Percentage of Participants With Bone Lesions (Bone Evaluation) |  | Up to 36 months as a maximum | 
| Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) | An adverse event (AE) 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. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. | Up to 36 months as a maximum |