Last reviewed · How we verify

NCT03170882

A Study of Ixazomib, Given With Dexamethasone in Adults With Multiple Myeloma

Completed Phase 2 Results posted Last updated 20 December 2022
What this trial tests

Phase 2 trial testing Ixazomib in Relapsed and/or Refractory Multiple Myeloma in 122 participants. Completed in 26 November 2021.

Timeline
1 August 2017
Primary endpoint
1 August 2020
26 November 2021

Quick facts

Lead sponsorMillennium Pharmaceuticals, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment122
Start date1 August 2017
Primary completion1 August 2020
Estimated completion26 November 2021
Sites111 locations across Denmark, France, Italy, Netherlands, Greece, Russia, Belgium, Sweden

Drugs / interventions tested

Conditions studied

Sponsor

Millennium Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Relapsed and/or Refractory Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Primary · From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)

PFS: Time from randomization to first occurrence of confirmed progressive disease (PD) as assessed by investigator by International Myeloma Working Group(IMWG) response criteria/death from any cause, whichever occurs first. PD requires following: Increase of \>=25 % from nadir in: Serum M component (increase must be \>=0.5 gram per deciliter \[g/dl\]); Urine M-component (increase must be \>=200 milligram \[mg\]/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved free light chain (FLC) increase of \>10 mg/dl; In participants w

GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg4.83.745 – 8.542
Ixazomib 4 mg + Dexamethasone 20 mg7.13.943 – 11.138
Overall Survival (OS) Secondary · From date of randomization to death due to any cause (Up to approximately 3 years)

OS was defined as the time from randomization to death from any cause, up to 3 years are reported.

GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mgNA13.963 – NA
Ixazomib 4 mg + Dexamethasone 20 mg18.810.973 – NA
Percentage of Participants With Overall Response Secondary · From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)

Overall Response Rate (ORR) was defined as the percentage of participants who achieved partial response (PR), very good partial response (VGPR), or complete response (CR) based on laboratory results and IRC assessment using modified IMWG criteria. PR: \>=50% reduction of serum M protein + reduction in 24-hour urinary M protein by \>=90% or to \<200 mg/24-hour; if M protein is not measurable, \>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, \>=50% reduction in bone marrow plasma cells, when baseline value \>=30% and; if present at b

GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg4127 – 56
Ixazomib 4 mg + Dexamethasone 20 mg3827 – 50
Duration of Response (DOR) Secondary · From date of first documentation of CR, VGPR or PR until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)

DOR: Time from first documentation of CR/PR/VGPR to first documentation of PD. Per IMWG criteria, PR:\>=50% reduction of serum M protein+reduction in 24-hour urinary M protein by \>=90% to \<200 mg/24-hour or \>=50% decrease in difference between involved and uninvolved FLC levels/ \>=50% reduction in bone marrow plasma cells, if \>=30% at Baseline/ \>=50% reduction in size of soft tissue plasmacytomas. VGPR: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR:negative immunofixation on

GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg14.33.713 – NA
Ixazomib 4 mg + Dexamethasone 20 mg14.810.152 – 19.614
Time to Response Secondary · From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)

Time to response was defined as the time from randomization to the first documentation of PR/VGPR/CR. Per IMWG criteria, PR: \>=50% reduction of serum M protein + reduction in 24-hour urinary M protein by \>=90% or to \<200 mg/24-hour; if M-protein is not measurable, \>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, \>=50% reduction in bone marrow plasma cells, when Baseline value \>=30% and; if present at Baseline, \>=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immun

GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg1.10.953 – 2.037
Ixazomib 4 mg + Dexamethasone 20 mg2.01.906 – 2.858
Time to Progression (TTP) Secondary · From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)

TTP was defined as the time from the date of randomization to first documentation of PD. Per IMWG criteria, PD required 1 of the following: Increase of \>=25% from nadir in: Serum M-component (increase must be \>=0.5 g/dl; Urine M-component (increase must be \>=200 mg/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved FLC levels increase of \>10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: Bone marrow plasma cell percentage must be \>=10%; Development

GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg5.13.844 – 12.485
Ixazomib 4 mg + Dexamethasone 20 mg8.45.684 – 13.306
Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score Secondary · Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

The 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/quality of life (QOL) scale. The physical domain consisted of 5 items covering participant's daily physical activities on a scale from 1 (not at all) to 4 (very much). Raw scores were linearly transformed to a total score between 0-100, with a high score indicating better physical functioning.

Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg67.0± 21.97
Ixazomib 4 mg + Dexamethasone 20 mg67.9± 22.08
End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg52.4± 28.03
Ixazomib 4 mg + Dexamethasone 20 mg56.5± 26.10
HRQOL Based on EORTC QLQ-C30 SubScale Score Secondary · Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

The 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 QOL scale. Most of the 30 items had 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Each subscale raw score were linearly transformed to a total score between 0 to 100. For the functional scales and the global health status/QOL scale, higher scores

Global Health Status/QoL: Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg57.0± 20.72
Ixazomib 4 mg + Dexamethasone 20 mg60.8± 21.16
Global Health Status/QoL: End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg47.8± 19.56
Ixazomib 4 mg + Dexamethasone 20 mg48.2± 19.61
Role (Functional Scale): Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg67.4± 28.42
Ixazomib 4 mg + Dexamethasone 20 mg67.9± 29.67
Role (Functional Scale): End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg47.6± 27.86
Ixazomib 4 mg + Dexamethasone 20 mg49.2± 27.04
Emotional (Functional Scale): Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg74.9± 21.19
Ixazomib 4 mg + Dexamethasone 20 mg83.1± 21.70
Emotional (Functional Scale): End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg67.6± 25.19
Ixazomib 4 mg + Dexamethasone 20 mg72.8± 22.62
Cognitive(Functional Scale): Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg79.6± 20.38
Ixazomib 4 mg + Dexamethasone 20 mg84.0± 20.74
Cognitive (Functional Scale): End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg69.6± 27.61
Ixazomib 4 mg + Dexamethasone 20 mg77.4± 22.64
HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score Secondary · Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 symptoms scales (disease symptoms, side effects of treatment), and 2 functional subscales (body image, future perspective). Scores were averaged and transformed to 0-100 scale. Higher scores for the future perspective scale indicate better perspective of the future, for the body image scale indicate better body image and for the disease symptoms scale indicate higher level of symptomatology.

Disease Symptoms: Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg73.2± 17.06
Ixazomib 4 mg + Dexamethasone 20 mg72.4± 21.31
Disease Symptoms: End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg73.5± 17.75
Ixazomib 4 mg + Dexamethasone 20 mg68.9± 23.09
Side Effects of Treatment: Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg81.0± 13.45
Ixazomib 4 mg + Dexamethasone 20 mg81.4± 13.30
Side Effects of Treatment: End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg74.4± 17.84
Ixazomib 4 mg + Dexamethasone 20 mg77.8± 14.47
Body Image: Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg81.5± 23.09
Ixazomib 4 mg + Dexamethasone 20 mg82.9± 23.90
Body Image: End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg75.0± 30.93
Ixazomib 4 mg + Dexamethasone 20 mg83.7± 23.71
Future Perspective: Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg58.8± 23.29
Ixazomib 4 mg + Dexamethasone 20 mg67.5± 24.03
Future Perspective: End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg57.9± 28.26
Ixazomib 4 mg + Dexamethasone 20 mg64.0± 19.21
Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score Secondary · End of Treatment (Up to 28 cycles, each cycle was of 28 days)

EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions.

Mobility: 1 = I Have no Problems in Walking About
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg5
Ixazomib 4 mg + Dexamethasone 20 mg9
Mobility: 2 = I Have Slight Problems in Walking About
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg6
Ixazomib 4 mg + Dexamethasone 20 mg12
Mobility: 3 = I Have Moderate Problems in Walking About
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg8
Ixazomib 4 mg + Dexamethasone 20 mg11
Mobility: 4 = I Have Severe Problems in Walking About
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg8
Ixazomib 4 mg + Dexamethasone 20 mg8
Mobility: 5 = I am Unable to Walk About
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg0
Ixazomib 4 mg + Dexamethasone 20 mg1
Self-Care: 1 = I Have no Problems Washing or Dressing Myself
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg13
Ixazomib 4 mg + Dexamethasone 20 mg21
Self-Care: 2 = I Have Slight Problems Washing or Dressing Myself
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg6
Ixazomib 4 mg + Dexamethasone 20 mg10
Self-Care: 3 = I Have Moderate Problems Washing or Dressing Myself
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg5
Ixazomib 4 mg + Dexamethasone 20 mg4
HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score Secondary · Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores from all dimensions were combined into a single index score that was reported, where higher score was better quality of life.

Baseline
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg59.2± 20.96
Ixazomib 4 mg + Dexamethasone 20 mg64.4± 18.21
End of Treatment
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg46.9± 19.07
Ixazomib 4 mg + Dexamethasone 20 mg55.9± 19.60
Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter Secondary · Up to approximately 3 years

Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice).

Hospitalizations
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg16
Ixazomib 4 mg + Dexamethasone 20 mg23
Emergency Room Stays
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg9
Ixazomib 4 mg + Dexamethasone 20 mg11
Outpatient Visits
GroupValue95% CI
Pomalidomide 4 mg + Dexamethasone 40 mg29
Ixazomib 4 mg + Dexamethasone 20 mg32

Adverse events — posted to ClinicalTrials.gov

Time frame: From signing of the informed consent up to 30 days after last dose of the study drug (Up to approximately 4 years 3 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pomalidomide 4 mg + Dexamethasone 40 mg
Serious: 26/47 (55%)
Deaths: 17/49
Ixazomib 4 mg + Dexamethasone 20 mg
Serious: 40/72 (56%)
Deaths: 29/73

Serious adverse events (75 terms)

ReactionSystemPomalidomide 4 mg + Dexame…Ixazomib 4 mg + Dexamethas…
PneumoniaInfections and infestations
Plasma cell myelomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Urinary tract infectionInfections and infestations
Atrial fibrillationCardiac disorders
ThrombocytopeniaBlood and lymphatic system disorders
BronchitisInfections and infestations
Respiratory syncytial virus infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
Gastrointestinal toxicityGastrointestinal disorders
HypercalcaemiaMetabolism and nutrition disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Lower respiratory tract infectionInfections and infestations
InfluenzaInfections and infestations
H1N1 influenzaInfections and infestations
Pneumonia influenzalInfections and infestations
Respiratory syncytial virus bronchitisInfections and infestations
Febrile infectionInfections and infestations
InfectionInfections and infestations
Neutropenic infectionInfections and infestations
SepsisInfections and infestations
BacteraemiaInfections and infestations
Respiratory tract infection viralInfections and infestations
Viral infectionInfections and infestations
DiverticulitisInfections and infestations
Other adverse events (42 terms — click to expand)

ReactionSystemPomalidomide 4 mg + Dexame…Ixazomib 4 mg + Dexamethas…
DiarrhoeaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
Peripheral sensory neuropathyNervous system disorders
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
InsomniaPsychiatric disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
ConstipationGastrointestinal disorders
Platelet count decreasedInvestigations
AstheniaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
Upper respiratory tract infectionInfections and infestations
BronchitisInfections and infestations
Bone painMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Urinary tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
HypokalaemiaMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Atrial fibrillationCardiac disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
PneumoniaInfections and infestations
HeadacheNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
Neutrophil count decreasedInvestigations
Rash maculo-papularSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
Influenza like illnessGeneral disorders
NasopharyngitisInfections and infestations

Most-reported serious reactions: Pneumonia, Plasma cell myeloma, Urinary tract infection, Atrial fibrillation, Thrombocytopenia, Bronchitis, Respiratory syncytial virus infection, Diarrhoea.

Data from ClinicalTrials.gov NCT03170882 adverse events section.

Sponsor's own description

The main aim of this study is to learn if ixazomib, given with dexamethasone, stops the cancer from getting worse in people with relapsed or refractory multiple myeloma. It will be compared to another medicine called pomalidomide, given with dexamethasone with people with the same condition. Relapsed means the previous cancer treatment stopped working, over time. Refractory means they did not respond to previous cancer treatment. Another aim is to check for side effects from the study medicines. At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 treatments by chance. * Ixazomib capsules, given with dexamethasone tablets * Pomalidomide capsules, given with dexamethasone tablets All participants will take their study medicine on specific days during a 28-day cycle. The 1st dose of study medicines in each 28-day cycle will take place in the clinic, The other doses of the study medicines will be taken at home. This will happen for 6 cycles. After this, all study medicines will be taken at home. After treatment, participants will visit the clinic every 12 weeks for a check-up. If participants cannot attend their clinic for an important reason (for example, due to the COVID-19 pandemic), the clinic will make alternative arrangements using their local procedures.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review.
    Hu S, Jiang S, Qi X, Bai R, et al · · 2022 · cited 68× · PMID 34762760 · DOI 10.1002/ddr.21895
  2. The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies.
    Hernández-Rivas JÁ, Ríos-Tamayo R, Encinas C, Alonso R, et al · · 2022 · cited 28× · PMID 35000618 · DOI 10.1186/s40364-021-00344-2
  3. Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase 2 trial.
    Dimopoulos MA, Schjesvold F, Doronin V, Vinogradova O, et al · · 2022 · cited 13× · PMID 35075109 · DOI 10.1038/s41408-021-00593-2
  4. Ikaros Proteins in Tumor: Current Perspectives and New Developments.
    Xia R, Cheng Y, Han X, Wei Y, et al · · 2021 · cited 12× · PMID 34950704 · DOI 10.3389/fmolb.2021.788440
  5. Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.
    Mina R, Mylin AK, Yokoyama H, Magen H, et al · · 2025 · cited 8× · PMID 39756844 · DOI 10.1016/s2352-3026(24)00320-x

Verify or expand the search:

Other trials of Ixazomib

Trials testing the same drug.

Other recruiting trials for Relapsed and/or Refractory Multiple Myeloma

Currently open trials in the same condition.

Other Millennium Pharmaceuticals, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03170882.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing