A Phase 3 interventional study of IXAZOMIB and Dexamethasone in Relapsed or Refractory Systemic Light Chain Amyloidosis, sponsored by Millennium Pharmaceuticals, Inc.. Terminated at 66 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-09-02.
Sponsored by Millennium Pharmaceuticals, Inc. (part of Takeda) · Phase 3, Interventional, and Treatment
The purpose of this study is to provide continued access of ixazomib and/or other study medications and to continue collecting relevant safety data to monitor participant's safety, determine whether dexamethasone plus IXAZOMIB improves hematologic response, 2-year vital organ (that is, heart or kidney) deterioration and mortality rate versus a physician's choice of a chemotherapy regimen in participants diagnosed with relapsed or refractory systemic light chain (AL) amyloidosis.
The drug being tested in this study is called IXAZOMIB. IXAZOMIB was being tested to treat people who have relapsed or Refractory Systemic Light Chain (AL) Amyloidosis.
The study will enroll approximately 177 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:
Physician's choice: Participants will receive one of the following treatment options as selected by the physician:
This multi-center trial will be conducted worldwide. The overall time to participate in this study is 120 months (10 years), including 84 months of enrollment and 36 months of follow-up after the last participant is enrolled.
290 studies on the registry are indexed under Amyloidosis; 92 are open to participants now.
This study's enrollment of 177 is above the median of 46 across 189 interventional studies indexed under Amyloidosis.
Browse Amyloidosis studies →Millennium Pharmaceuticals, Inc. is the lead sponsor of 178 studies on the registry; none are open to participants now.
Of its 74 completed or terminated interventional studies of FDA-regulated products, 73 (99%) have results posted.
First submitted after Millennium Pharmaceuticals, Inc. became part of Takeda.
Compared within Amyloidosis, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Recurrence. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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.
-proven diagnosis of primary systemic light chain amyloidosis (AL amyloidosis) according to the following standard criteria:
Objective, measurable major (cardiac or renal) organ amyloid involvement as defined as follows (amyloid involvement of at least 1 required):
Note: Amyloid involvement of other organ systems is allowed, but not required.
Must be after 1 or 2 prior therapies. For this protocol, relapsed is defined as progressive disease (PD) documented more than 60 days after last dose; refractory is defined as documented absence of hematologic response or hematologic progression on or within 60 days after last dose of prior therapy.
Must meet criteria for 1 of the following AL Amyloidosis Risk Stages (as defined by N-terminal proBNP [NT-proBNP] cut-off of \< 332 pg/mL and troponin T cut-off of 0.035 ng/mL as thresholds):
Clinical laboratory values:
Female participants who:
Male participants, even if surgically sterilized (ie, status post vasectomy), who:
Exclusion Criteria:
Clinically overt multiple myeloma, according to the International Myeloma Working Group (IMWG) criteria with at least 1 of the following:
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 biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
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.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
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.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
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.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
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.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
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.
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.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
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.
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.
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.
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.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
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.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
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.
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.
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.
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.
Ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 and dexamethasone 20 mg, orally, once weekly on Days 1, 8, 15, and 22 of each 28-day cycle for up to a maximum of 95.2 months. Dexamethasone was increased up to 40 mg/day after 4 weeks, if tolerated.
Drug: IXAZOMIB · Drug: Dexamethasone
Participants received dexamethasone 20 mg, orally, and melphalan 0.22 mg/kg, orally once on Days 1 through 4 of each 28-day cycle, for up to a maximum of 72.4 months.
Drug: Dexamethasone · Drug: Melphalan
Participants received dexamethasone 20 mg, orally, once weekly on Days 1, 8, 15, and 22, and cyclophosphamide 500 mg, orally, on Days 1, 8 and 15 of each 28-day cycle for up to a maximum of 72.4 months.
Drug: Dexamethasone · Drug: Cyclophosphamide
Participants received dexamethasone 20 mg, orally, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle, and thalidomide daily at a starting dose of 50 mg and increased, as tolerated, to a maximum of 200 mg, orally for up to a maximum of 72.4 months.
Drug: Dexamethasone · Drug: Thalidomide
Participants received dexamethasone 20 mg, orally, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle and lenalidomide 15 mg, orally, once on Days 1 through 21 every 28 days for up to a maximum of 72.4 months.
Drug: Dexamethasone · Drug: Lenalidomide
IXAZOMIB capsules
Also known as: MLN9708
Dexamethasone tablets
Melphalan tablets
Cyclophosphamide tablets
Thalidomide capsules
Lenalidomide capsules
Percentage of Participants With Overall Hematologic Response
Overall hematologic response was defined as the percentage of participants with complete response (CR), very good partial response (VGPR) and partial response (PR) based on central laboratory results and the 2010 International Society of Amyloidosis (ISA) Consensus Criteria as assessed by an adjudication committee. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of free light chain (FLC) ratio. VGPR: differential free light chain (difference between involved and uninvolved FLC levels; dFLC) \< 40 mg/L. PR: ≥50% reduction in dFLC. Percentages were rounded off to the nearest decimal.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
2-Year Vital Organ (Heart or Kidney) Deterioration and Mortality Rate
Cardiac (Heart) deterioration was defined as the need for hospitalization for heart failure. Kidney deterioration was defined as progression to end-stage renal disease (ESRD) with the need for maintenance dialysis or renal transplantation. Vital organ deterioration was evaluated by an adjudication committee. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: Up to 2 years
Percentage of Participants With Complete Hematologic Response
Complete hematologic response was defined as the percentage of participants with CR based on central laboratory results and the 2010 ISA Consensus Criteria as assessed by the investigator. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of FLC ratio. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Overall Survival
Overall survival was defined as the time from the date of randomization to the date of death. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of first documentation of hematologic disease progression, or organ (cardiac or renal) progression, or death due to any cause, whichever occurred first according to central laboratory results and ISA criteria as evaluated by the investigator. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Hematologic Disease Progression Free Survival
Hematologic disease PFS was defined as the time from the date of randomization to the date of first documentation of hematologic PD according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurred first. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Time to Vital Organ (Heart or Kidney) Deterioration and Mortality Rate
Time to vital organ deterioration or death was assessed by the investigator and defined as the time from randomization to vital organ (heart or kidney) deterioration or death, whichever occurs first. Cardiac deterioration is defined as the need for hospitalization for heart failure. Kidney deterioration is defined as progression to ESRD with the need for maintenance dialysis or renal transplantation. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From randomization to time of vital organ deterioration or death (up to 115 months)
Percentage of Participants With Best Vital Organ (Cardiac and/or Kidney) Response
Vital organ (heart and kidney) response rate was defined as the percentage of participants who achieved vital organ response according to central laboratory results and ISA criteria as evaluated by an adjudication committee. A vital organ response was defined as response of 1 or 2 of the involved vital organs with no change from Baseline in the rest of involved vital organs. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Vital Organ Progression Free Survival
Vital organ PFS is defined as the time from the date of randomization to the date of first documentation of progression of vital organ (heart or kidney) according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurs first. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Duration of Hematologic Response
Duration of hematologic response (DOR) was defined as the time from the date of first documentation of a hematologic response to the date of first documented hematologic disease progression as determined by the investigator. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From time of first documented response to disease progression (up to 115 months)
Number of Participants With Serious Adverse Events (SAEs)
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect or medically important event.
Time frame: From first dose of study drug through 30 days after administration of the last dose of study drug (up to 115 months)
Time To Treatment Failure (TTF)
TTF was defined as the time from randomization to the date of first documented treatment failure. Treatment failure was defined as: 1) death due to any cause; 2) hematologic progression or major organ progression according to central laboratory results and ISA criteria as evaluated by the investigator; 3) clinically morbid organ disease requiring additional therapy; or 4) withdrawn for any reason. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Time To Subsequent Anticancer Treatment
Time to subsequent anticancer therapy was defined as the time from randomization to the first date of subsequent anticancer therapy. Participants without subsequent anticancer therapy were censored at the date of death or last known to be alive. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until subsequent anticancer treatment (up to 115 months)
Change From Baseline in 36-item Short Form General Health Survey (SF-36) Mental Component Summary Score at Week 28 of the PFS Follow-up
SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: Baseline, Week 28 of the PFS Follow-up
Change From Baseline in SF-36 Physical Component Summary Score at Week 28 of the PFS Follow-up
SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: Baseline, Week 28 of the PFS Follow-up
Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Score at Week 28 of the PFS Follow-up
The FACT/GOG-Ntx is a participant completed questionnaire that comprises 11 individual items evaluating symptoms of neurotoxicity on a 5-point scale where: 0=not at all (best) to 4=very much for a total possible score of 0 to 44. Symptom scores are inverted so that higher scores of FACT/GOG-Ntx indicate higher quality of life or functioning. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: Baseline, Week 28 of the PFS Follow-up
Change From Baseline in Amyloidosis Symptom Scale Total Score at Week 28 of the PFS Follow-up
The amyloidosis symptom scale questionnaire is a participant completed questionnaire that evaluates symptom severity of 3 symptoms: Swelling, Shortness of Breath and Dizziness, each rated on an 11-point scale where: 0=no symptoms to 10=very severe symptoms. Higher scores indicate worsening of symptoms. Total Score is the sum of all responses from the amyloidosis symptom scale ranging from 0 to 30. Higher scores represent higher levels of symptomatology or problems and a negative change from baseline indicates improvement. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: Baseline, Week 28 of the PFS Follow-up
Number of Participants in Each Category of the EuroQol 5-Dimensional (EQ-5D) Questionnaire Score
The European Quality of Life (EuroQOL) 5-Dimensional (EQ-5D) is a patient completed questionnaire consisting of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 3 possible choices: no problems to extreme problems. Higher scores=worsening of the quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: At Week 28 of the OS follow-up
EuroQol 5-Dimension 3-Level (EQ-5D-3L) Visual Analogue Scale Score
The EQ visual analogue scale (VAS) records the participant's self-rated health on a 20 centimeter vertical VAS that ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Baseline is defined as the value collected at the time closest to, but prior to, the start of study drug administration. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: At Week 28 of the OS follow-up
Plasma Concentration of Ixazomib
As prespecified in the protocol, data for this outcome measure was planned to be collected for ixazomib arm group only.
Time frame: Cycle 1, Day 1: 1, 4 hours postdose, Day 14: 144 hours postdose; Cycle 2, Day 1: predose, Day 14: 144 hours postdose; Cycles 3 to 10, Day 1: predose (cycle length=28 days)
Number of Hospitalizations
A hospitalization was defined as at least one overnight stay in an intensive care unit and/or non-intensive care unit. If a single hospitalization included both an intensive care unit stay and a non-intensive care unit stay, the hospitalization was counted only once (as an intensive care unit stay). The mean number of hospitalizations is reported in this outcome measure. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Time frame: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Participants took part in the study at 66 investigative sites from 12 December 2012 to 11 July 2022. The study was prematurely terminated based on the Sponsor's decision following the first interim analysis.
| Milestone | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide |
|---|---|---|---|---|---|
| Started | 90 | 26 | 10 | 2 | 49 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 90 | 26 | 10 | 2 | 49 |
| Withdrew: Withdrawal by patient | 18 | 4 | 2 | 0 | 11 |
| Withdrew: Study terminated by sponsor | 9 | 7 | 0 | 1 | 4 |
| Withdrew: Reason not specified | 61 | 15 | 8 | 1 | 34 |
| Withdrew: Lost to follow-up | 2 | 0 | 0 | 0 | 0 |
Overall hematologic response was defined as the percentage of participants with complete response (CR), very good partial response (VGPR) and partial response (PR) based on central laboratory results and the 2010 International Society of Amyloidosis (ISA) Consensus Criteria as assessed by an adjudication committee. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of free light chain (FLC) ratio. VGPR: differential free light chain (difference between involved and uninvolved FLC levels; dFLC) \< 40 mg/L. PR: ≥50% reduction in dFLC. Percentages were rounded off to the nearest decimal.
| percentage of participants | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide |
|---|---|---|---|---|---|
| Percentage of Participants With Overall Hematologic Response | 53 (41.8 to 63.9) | 58 (36.6 to 77.9) | 30 (6.7 to 65.2) | 50 (1.3 to 98.7) | 51 (36.1 to 65.9) |
Cardiac (Heart) deterioration was defined as the need for hospitalization for heart failure. Kidney deterioration was defined as progression to end-stage renal disease (ESRD) with the need for maintenance dialysis or renal transplantation. Vital organ deterioration was evaluated by an adjudication committee. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| percentage of participants | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| 2-Year Vital Organ (Heart or Kidney) Deterioration and Mortality Rate | 47 (36.1 to 58.2) | 54 (41.7 to 64.1) |
Complete hematologic response was defined as the percentage of participants with CR based on central laboratory results and the 2010 ISA Consensus Criteria as assessed by the investigator. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of FLC ratio. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| percentage of participants | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Percentage of Participants With Complete Hematologic Response | 30 (20.8 to 40.6) | 17 (10.0 to 26.8) |
Overall survival was defined as the time from the date of randomization to the date of death. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| months | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Overall Survival | 69.55 (0.8 to 95.5) | 43.17 (0.0 to 82.4) |
PFS was defined as the time from the date of randomization to the date of first documentation of hematologic disease progression, or organ (cardiac or renal) progression, or death due to any cause, whichever occurred first according to central laboratory results and ISA criteria as evaluated by the investigator. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| months | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Progression Free Survival (PFS) | 11.86 (0.8 to 72.0) | 7.62 (0.0 to 71.1) |
Hematologic disease PFS was defined as the time from the date of randomization to the date of first documentation of hematologic PD according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurred first. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| months | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Hematologic Disease Progression Free Survival | 29.50 (0.1 to 54.5) | 27.73 (0.1 to 43.5) |
Time to vital organ deterioration or death was assessed by the investigator and defined as the time from randomization to vital organ (heart or kidney) deterioration or death, whichever occurs first. Cardiac deterioration is defined as the need for hospitalization for heart failure. Kidney deterioration is defined as progression to ESRD with the need for maintenance dialysis or renal transplantation. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| months | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Time to Vital Organ (Heart or Kidney) Deterioration and Mortality Rate | 38.67 (0.0 to 70.5) | 26.09 (0.0 to 71.1) |
Vital organ (heart and kidney) response rate was defined as the percentage of participants who achieved vital organ response according to central laboratory results and ISA criteria as evaluated by an adjudication committee. A vital organ response was defined as response of 1 or 2 of the involved vital organs with no change from Baseline in the rest of involved vital organs. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| percentage of participants | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Percentage of Participants With Best Vital Organ (Cardiac and/or Kidney) Response | 19 (11.2 to 28.8) | 12 (5.9 to 21.0) |
Vital organ PFS is defined as the time from the date of randomization to the date of first documentation of progression of vital organ (heart or kidney) according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurs first. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| months | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Vital Organ Progression Free Survival | 15.77 (0.0 to 72.0) | 11.01 (0.0 to 71.1) |
Duration of hematologic response (DOR) was defined as the time from the date of first documentation of a hematologic response to the date of first documented hematologic disease progression as determined by the investigator. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| months | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Duration of Hematologic Response | NA (1.8 to 71.1) | 21.19 (0.0 to 69.0) |
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect or medically important event.
| Participants | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide |
|---|---|---|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) | 44 | 11 | 2 | 0 | 17 |
TTF was defined as the time from randomization to the date of first documented treatment failure. Treatment failure was defined as: 1) death due to any cause; 2) hematologic progression or major organ progression according to central laboratory results and ISA criteria as evaluated by the investigator; 3) clinically morbid organ disease requiring additional therapy; or 4) withdrawn for any reason. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| months | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Time To Treatment Failure (TTF) | 10.32 (7.52 to 14.82) | 5.32 (4.14 to 7.82) |
Time to subsequent anticancer therapy was defined as the time from randomization to the first date of subsequent anticancer therapy. Participants without subsequent anticancer therapy were censored at the date of death or last known to be alive. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| months | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Time To Subsequent Anticancer Treatment | 26.48 (0.8 to 95.5) | 12.45 (0.0 to 72.7) |
SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| score on a scale | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Change From Baseline in 36-item Short Form General Health Survey (SF-36) Mental Component Summary Score at Week 28 of the PFS Follow-up | — | 2.0 ± NA |
SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| score on a scale | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Change From Baseline in SF-36 Physical Component Summary Score at Week 28 of the PFS Follow-up | — | 10.3 ± NA |
The FACT/GOG-Ntx is a participant completed questionnaire that comprises 11 individual items evaluating symptoms of neurotoxicity on a 5-point scale where: 0=not at all (best) to 4=very much for a total possible score of 0 to 44. Symptom scores are inverted so that higher scores of FACT/GOG-Ntx indicate higher quality of life or functioning. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| score on a scale | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Score at Week 28 of the PFS Follow-up | — | 0.0 ± NA |
The amyloidosis symptom scale questionnaire is a participant completed questionnaire that evaluates symptom severity of 3 symptoms: Swelling, Shortness of Breath and Dizziness, each rated on an 11-point scale where: 0=no symptoms to 10=very severe symptoms. Higher scores indicate worsening of symptoms. Total Score is the sum of all responses from the amyloidosis symptom scale ranging from 0 to 30. Higher scores represent higher levels of symptomatology or problems and a negative change from baseline indicates improvement. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| score on a scale | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Change From Baseline in Amyloidosis Symptom Scale Total Score at Week 28 of the PFS Follow-up | — | -16.0 ± NA |
The European Quality of Life (EuroQOL) 5-Dimensional (EQ-5D) is a patient completed questionnaire consisting of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 3 possible choices: no problems to extreme problems. Higher scores=worsening of the quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| Participants | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Mobility: No Problems in Walking About | 0 | 0 |
| Mobility: Some Problem in Walking About | 0 | 1 |
| Mobility: Confined to Bed | 0 | 0 |
| Self-Care: No Problems With Self- Care | 0 | 0 |
| Self-Care: Some Problems Washing or Dressing | 0 | 1 |
| Self-Care: Unable to Wash or Dress | 0 | 0 |
| Usual Activities: No Problems With Performing Usual Activities | 0 | 0 |
| Usual Activities: Some Problem With Performing Usual Activities | 0 | 1 |
| Usual Activities: Unable to Performing Usual Activities | 0 | 0 |
| Pain/Discomfort: No Pain or Discomfort | 0 | 0 |
| Pain/Discomfort: Moderate Pain or Discomfort | 0 | 1 |
| Pain/Discomfort: Extreme Pain or Discomfort | 0 | 0 |
| Anxiety/Depression: Not Anxious or Depressed | 0 | 0 |
| Anxiety/Depression: Moderately Anxious or Depressed | 0 | 0 |
| Anxiety/Depression: Extremely Anxious or Depressed | 0 | 1 |
The EQ visual analogue scale (VAS) records the participant's self-rated health on a 20 centimeter vertical VAS that ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Baseline is defined as the value collected at the time closest to, but prior to, the start of study drug administration. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| score on a scale | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| EuroQol 5-Dimension 3-Level (EQ-5D-3L) Visual Analogue Scale Score | — | 23.0 ± NA |
As prespecified in the protocol, data for this outcome measure was planned to be collected for ixazomib arm group only.
| nanogram per milliliter (ng/mL) | Arm A: Ixazomib + Dexamethasone |
|---|---|
| Cycle 1 Day 1: 1 Hour Post-dose | 16.518 ± 97.0462 |
| Cycle 1 Day 14: 4 Hours Post-dose | 10.652 ± 121.7231 |
| Cycle 1 Day 14: 144 Hours Post-dose | 3.875 ± 100.3055 |
| Cycle 2 Day 1: Pre-dose | 2.000 ± 59.4061 |
| Cycle 2 Day 14: 144 Hours Post-dose | 4.726 ± 115.5653 |
| Cycle 3 Day 1: Pre-dose | 2.187 ± 59.1378 |
| Cycle 4 Day 1 Pre-dose | 2.276 ± 59.3690 |
| Cycle 5 Day 1 Pre-dose | 2.264 ± 54.8881 |
| Cycle 6 Day 1: Pre-dose | 2.235 ± 60.4723 |
| Cycle 7 Day 1: Pre-dose | 2.299 ± 53.7147 |
| Cycle 8 Day 1: Pre-dose | 2.038 ± 58.6811 |
| Cycle 9 Day 1: Pre-dose | 2.143 ± 55.0715 |
| Cycle 10 Day 1: Pre-dose | 2.232 ± 57.4067 |
A hospitalization was defined as at least one overnight stay in an intensive care unit and/or non-intensive care unit. If a single hospitalization included both an intensive care unit stay and a non-intensive care unit stay, the hospitalization was counted only once (as an intensive care unit stay). The mean number of hospitalizations is reported in this outcome measure. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
| hospitalizations | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide |
|---|---|---|
| Number of Hospitalizations | 1.8 ± 1.34 | 1.4 ± 0.80 |
Collected over From first dose of study drug through 30 days after administration of the last dose of study drug (up to 115 months). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A: Ixazomib + Dexamethasone | 40/90 (44.4%) | 44/90 (48.9%) | 86/90 (95.6%) |
| Arm B: Dexamethasone + Melphalan | 14/26 (53.8%) | 11/26 (42.3%) | 24/26 (92.3%) |
| Arm B: Dexamethasone + Cyclophosphamide | 4/10 (40%) | 2/10 (20%) | 9/10 (90%) |
| Arm B: Dexamethasone + Thalidomide | 0/2 (0%) | 0/1 (0%) | 1/1 (100%) |
| Arm B: Dexamethasone + Lenalidomide | 22/49 (44.9%) | 17/47 (36.2%) | 46/47 (97.9%) |
| Event | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide |
|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 5/90 | 4/26 | 0/10 | 0/1 | 2/47 |
| Acute kidney injuryRenal and urinary disorders | 2/90 | 0/26 | 1/10 | 0/1 | 0/47 |
| Cardiac failureCardiac disorders | 4/90 | 0/26 | 1/10 | 0/1 | 1/47 |
| CellulitisInfections and infestations | 4/90 | 0/26 | 0/10 | 0/1 | 0/47 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 4/90 | 0/26 | 0/10 | 0/1 | 1/47 |
| Lower respiratory tract infectionInfections and infestations | 0/90 | 1/26 | 0/10 | 0/1 | 2/47 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 2/90 | 1/26 | 0/10 | 0/1 | 2/47 |
| Septic shockInfections and infestations | 0/90 | 0/26 | 0/10 | 0/1 | 2/47 |
| Abscess limbInfections and infestations | 0/90 | 1/26 | 0/10 | 0/1 | 0/47 |
| Angina pectorisCardiac disorders | 0/90 | 1/26 | 0/10 | 0/1 | 0/47 |
| Event | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide |
|---|---|---|---|---|---|
| ConstipationGastrointestinal disorders | 18/90 | 3/26 | 4/10 | 1/1 | 13/47 |
| Dry skinSkin and subcutaneous tissue disorders | 4/90 | 1/26 | 0/10 | 1/1 | 1/47 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 19/90 | 3/26 | 0/10 | 1/1 | 12/47 |
| FatigueGeneral disorders | 40/90 | 7/26 | 3/10 | 1/1 | 24/47 |
| InfluenzaInfections and infestations | 7/90 | 1/26 | 1/10 | 1/1 | 3/47 |
| InsomniaPsychiatric disorders | 32/90 | 3/26 | 2/10 | 1/1 | 8/47 |
| Muscle spasmsMusculoskeletal and connective tissue disorders | 9/90 | 1/26 | 0/10 | 1/1 | 7/47 |
| MyopiaEye disorders | 0/90 | 0/26 | 0/10 | 1/1 | 0/47 |
| Peripheral sensory neuropathyNervous system disorders | 20/90 | 0/26 | 0/10 | 1/1 | 10/47 |
| PneumoniaInfections and infestations | 3/90 | 0/26 | 0/10 | 1/1 | 0/47 |
Intent-to-Treat (ITT) Population included all participants who were randomized.
| Age, Continuous(years) | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide | Total |
|---|---|---|---|---|---|---|
| Mean | 63.4 ± 9.83 | 64.8 ± 8.73 | 60.0 ± 14.97 | 65.0 ± 2.83 | 64.9 ± 8.68 | 63.9 ± 9.65 |
| Sex: Female, Male(Participants) | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide | Total |
|---|---|---|---|---|---|---|
| Female | 35 | 11 | 4 | 2 | 22 | 74 |
| Male | 55 | 15 | 6 | 0 | 27 | 103 |
| Ethnicity (NIH/OMB)(Participants) | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 0 | 0 | 2 | 3 |
| Not Hispanic or Latino | 85 | 25 | 9 | 2 | 40 | 161 |
| Unknown or Not Reported | 5 | 0 | 1 | 0 | 7 | 13 |
| Race (NIH/OMB)(Participants) | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 16 | 9 | 5 | 1 | 1 | 32 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 0 | 0 | 0 | 1 |
| White | 70 | 17 | 5 | 1 | 48 | 141 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 0 | 0 | 0 | 0 | 3 |
| Region of Enrollment(Participants) | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide | Total |
|---|---|---|---|---|---|---|
| Canada | 5 | 0 | 1 | 0 | 3 | 9 |
| United States | 24 | 2 | 3 | 0 | 13 | 42 |
| Czechia | 2 | 0 | 0 | 0 | 1 | 3 |
| Denmark | 0 | 0 | 0 | 1 | 2 | 3 |
| France | 3 | 1 | 0 | 0 | 1 | 5 |
| Germany | 8 | 5 | 0 | 0 | 3 | 16 |
| United Kingdom | 10 | 4 | 0 | 0 | 3 | 17 |
| Greece | 6 | 0 | 2 | 0 | 7 | 15 |
| Italy | 3 | 0 | 0 | 0 | 4 | 7 |
| Netherlands | 3 | 1 | 0 | 0 | 0 | 4 |
| Spain | 1 | 1 | 0 | 0 | 3 | 5 |
| Turkey | 1 | 0 | 0 | 0 | 0 | 1 |
| Australia | 8 | 0 | 0 | 0 | 6 | 14 |
| Brazil | 0 | 0 | 0 | 1 | 0 | 1 |
| China | 4 | 2 | 0 | 0 | 0 | 6 |
| Israel | 3 | 3 | 0 | 0 | 2 | 8 |
| Japan | 2 | 5 | 0 | 0 | 0 | 7 |
| Korea, Republic of | 7 | 2 | 4 | 0 | 1 | 14 |
| Height(centimeters (cm)) | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide | Total |
|---|---|---|---|---|---|---|
| Mean | 170.40 ± 10.507 | 167.07 ± 8.662 | 170.65 ± 13.274 | 160.50 ± 13.435 | 169.17 ± 10.532 | 169.48 ± 10.444 |
| Weight(kilograms (kg)) | Arm A: Ixazomib + Dexamethasone | Arm B: Dexamethasone + Melphalan | Arm B: Dexamethasone + Cyclophosphamide | Arm B: Dexamethasone + Thalidomide | Arm B: Dexamethasone + Lenalidomide | Total |
|---|---|---|---|---|---|---|
| Mean | 77.33 ± 16.740 | 70.95 ± 12.476 | 70.20 ± 21.815 | 50.10 ± 15.415 | 75.35 ± 17.144 | 75.13 ± 16.830 |
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 Dec 2012 to primary completion in Jul 2022, 114 months.
Results were first posted in Sep 2023, 1 year 2 months after primary completion.
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Studies of the drug tested here: Ixazomib
Millennium Pharmaceuticals, Inc. →