A Phase 4 interventional study of Ixazomib and Bortezomib in Relapsed and/or Refractory Multiple Myeloma, sponsored by Takeda. Completed at 23 sites in Japan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2022-09-27.
Sponsored by Takeda · Phase 4, Interventional, and Treatment
Among 68 studies testing ixazomib in Multiple Myeloma — 1 open to participants now, 7 under way, none of them phase 3. ixazomib · Multiple Myeloma.
Among the 68 studies testing ixazomib in Multiple Myeloma, this one is the 36th largest by enrollment, is one of 8 that started in 2018, is one of 4 in phase 4, and was the 44th registered.
3,760 studies on the registry are indexed under Multiple Myeloma; 769 are open to participants now.
Browse Multiple Myeloma studies →1 of the 68 studies testing ixazomib in Multiple Myeloma is open now, in 1 country. Recruiting first, the newest first:
Second Affiliated Hospital, School of Medicine, Zhejiang University · Sites in China
By country, each count listing its studies:
ixazomib: first FDA approval 2015 (NINLARO), first EMA approval 2016. What it is approved for, and how studies give it, is on its page →
Of the 584 Multiple Myeloma studies recruiting now, 429 (73%) set no upper age limit and 106 (18%) stop at 75 or younger; 36 take children under 18; 24 take healthy volunteers.
This study: 20 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
68 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 18 · Phase 2 47 · Phase 3 8 · Phase 4 4
First in 2009; this study’s year is marked. 8 started in 2018.
This study's enrollment of 45 is close to the median of 41 across 3,005 interventional studies indexed under Multiple Myeloma.
Median enrollment 48 across the 68 interventional studies. Of the 55 that completed or were terminated, 38 (69%) have results posted.
This tab as a report to print or save as PDF → With an account.
22 of 68 have an industry lead sponsor. The 10 most frequent:
Takeda is the lead sponsor of 1,026 studies on the registry; 89 are open to participants now.
Of its 178 completed or terminated interventional studies of FDA-regulated products, 154 (87%) have results posted.
27 studies in Multiple Myeloma by Takeda: 2 open now, 4 under way, 1 of them phase 3. Of 21 finished, 15 (71%) have results posted.
Among the 27 studies in Multiple Myeloma by Takeda, this one is the 8th largest by enrollment of the 14 interventional ones that give a count, is one of 4 that started in 2018, is one of 3 in phase 4, and was the 10th registered.
Takeda’s Multiple Myeloma studies by the year they started, since 2012.
2 of the studies testing ixazomib in Multiple Myeloma that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04009109Alliance Foundation Trials, LLC.Study of Lenalidomide/Ixazomib/Dexamethasone/Daratumumab in Transplant-Ineligible Patients With Newly Diagnosed MM | 2026-12 |
| NCT03763162M.D. Anderson Cancer CenterDaratumumab, Bortezomib, and Dexamethasone Followed by Daratumumab, Ixazomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma | 2027-10-30 |
Among the 68 studies testing ixazomib in Multiple Myeloma, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Takeda’s 27 in Multiple Myeloma:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
The purpose of this study is to investigate the efficacy and safety of long-term administration of the oral proteasome inhibitor ixazomib as part of ixazomib in combination with lenalidomide and dexamethasone (IRd) therapy in patients with relapsed and/or refractory multiple myeloma (RRMM) treated initially with an injectable proteasome inhibitor-based therapy.
The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have RRMM. This study will look at the effectiveness and safety of IRd in participants with RRMM previously receiving an injectable proteasome inhibitor-based therapy. This study consists of two treatment periods, Treatment Period I and Treatment Period II.
The study will enroll 47 patients. All participants will receive following treatment:
At start of this study, combination therapy of VRd or KRd will be decided by investigator as Treatment Period I after the baseline evaluations. After the start of Treatment Period I, a participant's eligibility for Treatment Period II is then determined 3 cycles. Participants who meet these eligibility criteria II subsequently continue into Treatment Period II and receive IRd.
This multi-center trial will be conducted in Japan. It is anticipated that the treatment phase of this study will last up to 39 months, including 18 months for enrollment. Participants will make multiple visits to the clinic in treatment period, and follow-up period including a follow-up assessment after last dose of study drug.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Eligibility for Treatment Period I
Participants with defined by one or more of the following three measurements.
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 .
Eligibility for Treatment Period II
Exclusion Criteria:
Eligibility for Treatment Period I
Participants who were 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.
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
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Drug: Ixazomib · Drug: Bortezomib · Drug: Carfilzomib · Drug: Lenalidomide · Drug: Dexamethasone
Ixazomib capsules
Bortezomib injections
Carfilzomib intravenous infusions
Lenalidomide capsules
Dexamethasone tablets
Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment
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.
Time frame: Up to 12 months
Overall Survival (OS) From the Start of Study Treatment
OS was 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) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier.
Time frame: Up to 39 months as a maximum
PFS From the Start of Study Treatment
PFS was 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 was assessed by IMWG Criteria.
Time frame: Up to 39 months as a maximum
Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)
VGPR or better (CR + VGPR) were 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 \<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 (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
Time frame: Up to 39 months as a maximum
Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR
MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive and negative in bone marrow in participants who achieved CR. MRD positive was categorized into three sensitivity levels with the numbers of cells counted (10\^-4 to - Max; 10\^-5 to 10\^-4; 10\^-6 to 10\^-5). MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria.
Time frame: Up to 39 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 PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥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 (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
Time frame: Up to 39 months as a maximum
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. Per IMWG criteria, PR (partial response): ≥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 (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
Time frame: Up to 39 months as a maximum
Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment
Time frame: 12 months
Duration of Response (DOR)
DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥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 (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
Time frame: Up to 39 months as a maximum
Time to Next Treatment (TTNT)
TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment.
Time frame: Up to 39 months as a maximum
Duration of Therapy (DOT)
DOT is defined as the treatment duration of study drug at study treatment Period I.
Time frame: Up to 39 months as a maximum
Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
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 (Global Health Status). 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 are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
Time frame: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, 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 functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.
Time frame: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)
Evaluation of Modified Quality-Adjusted Life-Years (QALYs)
Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY.
Time frame: Up to 39 months as a maximum
Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month
HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported.
Time frame: Up to 39 months as a maximum
Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants
HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported.
Time frame: Up to 39 months as a maximum
Relative Dose Intensity (RDI)
RDI for each study drug is defined as 100\*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals \[dose prescribed at enrollment\* number of prescribed doses per cycle\* the number of treated cycles\].
Time frame: Up to 39 months as a maximum
Percentage of Participants With Bone Lesions (Bone Evaluation)
Time frame: Up to 39 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.
Time frame: Up to 39 months as a maximum
Participant s took part in the survey at 33 investigative sites in Japan, from 18 February 2018 to 28 May 2021.
| Milestone | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy |
|---|---|---|
| Started | 6 | 39 |
| Completed | 0 | 0 |
| Not completed | 6 | 39 |
| Milestone | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy |
|---|---|---|
| Started | 6 | 39 |
| Completed | 6 | 30 |
| Not completed | 0 | 9 |
| Withdrew: Other | 0 | 9 |
| Milestone | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy |
|---|---|---|
| Started | 6 | 30 |
| Completed | 2 | 12 |
| Not completed | 4 | 18 |
| Withdrew: Lack of efficacy | 3 | 11 |
| Withdrew: Adverse event | 1 | 4 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Other | 0 | 2 |
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.
| Percentage of Participants | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment | 50.0 (15.3 to 84.7) | 48.7 (34.7 to 62.9) | 48.9 (35.9 to 62.0) |
OS was 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) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier.
| Months | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Overall Survival (OS) From the Start of Study Treatment | NA (16.00 to NA) | NA (NA to NA) | NA (NA to NA) |
PFS was 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 was assessed by IMWG Criteria.
| Months | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| PFS From the Start of Study Treatment | NA (4.86 to NA) | 28.96 (21.32 to NA) | 28.96 (21.32 to NA) |
VGPR or better (CR + VGPR) were 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 \<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 (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
| Percentage of Participants | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Percentage of Participants Who Achieved VGPR or Better (CR + VGPR) | 33.3 (4.3 to 77.7) | 43.6 (27.8 to 60.4) | 42.2 (27.7 to 57.8) |
MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive and negative in bone marrow in participants who achieved CR. MRD positive was categorized into three sensitivity levels with the numbers of cells counted (10\^-4 to - Max; 10\^-5 to 10\^-4; 10\^-6 to 10\^-5). MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria.
| Participants | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Sensitivity Level; 10^-4=< - Max | 0 | 1 | 1 |
| Sensitivity Level; 10^-5=< - <10^-4 | 1 | 2 | 3 |
| Sensitivity Level; 10^-6=< - <10^-5 | 1 | 1 | 2 |
| Negative | 0 | 5 | 5 |
Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥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 (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
| Percentage of Participants | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| CR | 33.3 | 23.1 | 24.4 |
| VGPR | 0 | 20.5 | 17.8 |
| PR | 50.0 | 28.2 | 31.1 |
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. Per IMWG criteria, PR (partial response): ≥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 (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
| Percentage of Participants | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Overall Response Rate (ORR) | 83.3 (35.9 to 99.6) | 71.8 (55.1 to 85.0) | 73.3 (58.1 to 85.4) |
| Percentage of Participants | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment | 50.0 (11.8 to 88.2) | 35.9 (21.2 to 52.8) | 37.8 (23.8 to 53.5) |
DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥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 (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
| Months | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Duration of Response (DOR) | 15.31 (3.64 to NA) | 28.03 (20.4 to NA) | 28.03 (20.4 to NA) |
TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment.
| Months | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Time to Next Treatment (TTNT) | 21.59 (4.99 to NA) | 32.26 (12.43 to 35.44) | 32.26 (14.88 to 35.44) |
DOT is defined as the treatment duration of study drug at study treatment Period I.
| Months | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Duration of Therapy (DOT) | 14.69 (4.86 to NA) | 12.43 (7.74 to 24.79) | 12.43 (8.86 to 24.79) |
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 (Global Health Status). 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 are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
| Score on a Scale | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Baseline | 44.44 ± 40.369 | 63.25 ± 24.085 | 60.74 ± 26.981 |
| Cycle 23 | 0 ± NA | 54.17 ± 8.740 | 46.43 ± 21.973 |
| Cycle 32 | — | 50.00 ± 23.750 | 50.00 ± 23.750 |
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 functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.
| Score on a Scale | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Disease Symptoms: Baseline | 24.07 ± 21.564 | 19.23 ± 16.756 | 19.88 ± 17.266 |
| Disease Symptoms: Cycle 23 | 0 ± NA | 4.63 ± 7.384 | 3.97 ± 6.964 |
| Disease Symptoms: Cycle 32 | — | 2.78 ± 3.928 | 2.78 ± 3.928 |
| Side-Effects of Treatment: Baseline | 16.67 ± 12.776 | 16.60 ± 14.464 | 16.61 ± 14.115 |
| Side-Effects of Treatment: Cycle 23 | 3.70 ± NA | 16.05 ± 3.825 | 14.29 ± 5.828 |
| Side-Effects of Treatment: Cycle 32 | — | 18.52 ± 15.713 | 18.52 ± 15.713 |
| Body Image: Baseline | 44.44 ± 45.542 | 23.08 ± 26.660 | 25.93 ± 30.058 |
| Body Image: Cycle 23 | 0 ± NA | 16.67 ± 18.257 | 14.29 ± 17.817 |
| Body Image: Cycle 32 | — | 16.67 ± 23.570 | 16.67 ± 23.570 |
| Future Perspective: Baseline | 66.67 ± 37.185 | 44.16 ± 24.114 | 47.16 ± 26.817 |
| Future Perspective: Cycle 23 | 11.11 ± NA | 35.19 ± 8.364 | 31.75 ± 11.878 |
| Future Perspective: Cycle 32 | — | 27.78 ± 7.857 | 27.78 ± 7.857 |
Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY.
| Quality-Adjusted Life-Years | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Evaluation of Modified Quality-Adjusted Life-Years (QALYs) | 0.467 (0.25 to 0.89) | 0.534 (0.17 to 0.85) | 0.518 (0.17 to 0.89) |
HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported.
| Number of Events per Participants-Month | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month | 1.9 | 2.9 | 2.7 |
HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported.
| Days | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants | 14.8 ± 16.01 | 19.4 ± 18.14 | 18.8 ± 17.77 |
RDI for each study drug is defined as 100\*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals \[dose prescribed at enrollment\* number of prescribed doses per cycle\* the number of treated cycles\].
| Percent | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|
| Bortezomib, Ixazomib | 71.93 (58.2 to 97.2) |
| Carfilzomib, Ixazomib | 87.70 (27.0 to 108.4) |
| Bortezomib/Carfilzomib, Ixazomib | 83.24 (27.0 to 108.4) |
| Lenalidomide | 47.18 (9.0 to 100.4) |
| Dexamethasone | 48.61 (6.6 to 105.3) |
| Percentage of Participants | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Percentage of Participants With Bone Lesions (Bone Evaluation) | 100.0 (29.2 to 100.0) | 59.1 (36.4 to 79.3) | 64.0 (42.5 to 82.0) |
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.
| Participants | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) | 6 | 35 | 41 |
Collected over Up to 39 months as a maximum. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 0/6 (0%) | 3/6 (50%) | 6/6 (100%) |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 2/39 (5.1%) | 14/39 (35.9%) | 31/39 (79.5%) |
| [Overall]; Combination Therapy + Ixazomib Therapy | 2/45 (4.4%) | 17/45 (37.8%) | 37/45 (82.2%) |
| Event | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| Compression fractureInjury, poisoning and procedural complications | 1/6 | 0/39 | 1/45 |
| Spinal compression fractureInjury, poisoning and procedural complications | 1/6 | 0/39 | 1/45 |
| Tibia fractureInjury, poisoning and procedural complications | 1/6 | 0/39 | 1/45 |
| Bone painMusculoskeletal and connective tissue disorders | 1/6 | 0/39 | 1/45 |
| PneumoniaInfections and infestations | 0/6 | 5/39 | 5/45 |
| InfluenzaInfections and infestations | 0/6 | 2/39 | 2/45 |
| Acute kidney injuryRenal and urinary disorders | 0/6 | 2/39 | 2/45 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/6 | 1/39 | 1/45 |
| Prinzmetal anginaCardiac disorders | 0/6 | 1/39 | 1/45 |
| Duodenal ulcerGastrointestinal disorders | 0/6 | 1/39 | 1/45 |
| Event | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | [Overall]; Combination Therapy + Ixazomib Therapy |
|---|---|---|---|
| RashSkin and subcutaneous tissue disorders | 4/6 | 3/39 | 7/45 |
| DiarrhoeaGastrointestinal disorders | 3/6 | 10/39 | 13/45 |
| Decreased appetiteMetabolism and nutrition disorders | 3/6 | 0/39 | 3/45 |
| NasopharyngitisInfections and infestations | 2/6 | 2/39 | 4/45 |
| White blood cell count decreasedInvestigations | 2/6 | 9/39 | 11/45 |
| Taste disorderNervous system disorders | 2/6 | 1/39 | 3/45 |
| Platelet count decreasedInvestigations | 1/6 | 8/39 | 9/45 |
| AnaemiaBlood and lymphatic system disorders | 1/6 | 3/39 | 4/45 |
| ConstipationGastrointestinal disorders | 1/6 | 3/39 | 4/45 |
| MalaiseGeneral disorders | 1/6 | 3/39 | 4/45 |
Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Age, Continuous(Years) | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total |
|---|---|---|---|
| Mean | 71.8 ± 8.57 | 70.5 ± 9.40 | 70.7 ± 9.21 |
| Sex: Female, Male(Participants) | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total |
|---|---|---|---|
| Female | 5 | 16 | 21 |
| Male | 1 | 23 | 24 |
| Race and Ethnicity Not Collected(Participants) | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(Participants) | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total |
|---|---|---|---|
| Japan | 6 | 39 | 45 |
| Height(Centimeters (cm)) | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total |
|---|---|---|---|
| Mean | 153.0 ± 9.70 | 158.5 ± 8.29 | 157.8 ± 8.58 |
| Weight(Kilograms (kg)) | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total |
|---|---|---|---|
| Mean | 52.85 ± 7.204 | 57.87 ± 10.380 | 57.17 ± 10.081 |
| BMI(Kilogram (kg)/meter (m)^2]) | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total |
|---|---|---|---|
| Mean | 22.60 ± 2.619 | 22.91 ± 2.512 | 22.86 ± 2.497 |
| Body Surface Area(m^2) | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total |
|---|---|---|---|
| Mean | 1.487 ± 0.1395 | 1.583 ± 0.1760 | 1.569 ± 0.1732 |
3 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Data sharing details ↗ · vivli.org
Ran from Feb 2018 to primary completion in May 2021, 39 months.
Results were first posted in Aug 2022, 1 year 2 months after primary completion.
Of 28 phase 4 interventional studies under Multiple Myeloma, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 30 and three quarters within 57. This study's 39 months is close to that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Ixazomib · Lenalidomide · Dexamethasone