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NCT03416374

A Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome Inhibitor-Based Therapy

Completed Phase 4 Results posted Last updated 27 September 2022
What this trial tests

Phase 4 trial testing Ixazomib in Relapsed and/or Refractory Multiple Myeloma in 45 participants. Completed in 28 May 2021.

Timeline
18 February 2018
Primary endpoint
28 May 2021
28 May 2021

Quick facts

Lead sponsorTakeda
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment45
Start date18 February 2018
Primary completion28 May 2021
Estimated completion28 May 2021
Sites23 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

20 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) Rate at 12 Months From the Start of Study Treatment Primary · Up to 12 months

PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase \>10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft ti

GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy50.015.3 – 84.7
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy48.734.7 – 62.9
[Overall]; Combination Therapy + Ixazomib Therapy48.935.9 – 62.0
Overall Survival (OS) From the Start of Study Treatment Secondary · Up to 39 months as a maximum

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.

GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone TherapyNA16.00 – NA
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone TherapyNANA – NA
[Overall]; Combination Therapy + Ixazomib TherapyNANA – NA
PFS From the Start of Study Treatment Secondary · Up to 39 months as a maximum

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.

GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone TherapyNA4.86 – NA
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy28.9621.32 – NA
[Overall]; Combination Therapy + Ixazomib Therapy28.9621.32 – NA
Percentage of Participants Who Achieved VGPR or Better (CR + VGPR) Secondary · Up to 39 months as a maximum

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

GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy33.34.3 – 77.7
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy43.627.8 – 60.4
[Overall]; Combination Therapy + Ixazomib Therapy42.227.7 – 57.8
Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR Secondary · Up to 39 months as a maximum

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

Sensitivity Level; 10^-4=< - Max
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy0
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy1
[Overall]; Combination Therapy + Ixazomib Therapy1
Sensitivity Level; 10^-5=< - <10^-4
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy1
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy2
[Overall]; Combination Therapy + Ixazomib Therapy3
Sensitivity Level; 10^-6=< - <10^-5
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy1
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy1
[Overall]; Combination Therapy + Ixazomib Therapy2
Negative
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy0
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy5
[Overall]; Combination Therapy + Ixazomib Therapy5
Percentage of Participants Who Achieve or Maintain Any Best Response Secondary · Up to 39 months as a maximum

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 detectab

CR
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy33.3
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy23.1
[Overall]; Combination Therapy + Ixazomib Therapy24.4
VGPR
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy0
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy20.5
[Overall]; Combination Therapy + Ixazomib Therapy17.8
PR
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy50.0
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy28.2
[Overall]; Combination Therapy + Ixazomib Therapy31.1
Overall Response Rate (ORR) Secondary · Up to 39 months as a maximum

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): seru

GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy83.335.9 – 99.6
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy71.855.1 – 85.0
[Overall]; Combination Therapy + Ixazomib Therapy73.358.1 – 85.4
Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment Secondary · 12 months
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy50.011.8 – 88.2
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy35.921.2 – 52.8
[Overall]; Combination Therapy + Ixazomib Therapy37.823.8 – 53.5
Duration of Response (DOR) Secondary · Up to 39 months as a maximum

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 detect

GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy15.313.64 – NA
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy28.0320.4 – NA
[Overall]; Combination Therapy + Ixazomib Therapy28.0320.4 – NA
Time to Next Treatment (TTNT) Secondary · Up to 39 months as a maximum

TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment.

GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy21.594.99 – NA
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy32.2612.43 – 35.44
[Overall]; Combination Therapy + Ixazomib Therapy32.2614.88 – 35.44
Duration of Therapy (DOT) Secondary · Up to 39 months as a maximum

DOT is defined as the treatment duration of study drug at study treatment Period I.

GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy14.694.86 – NA
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy12.437.74 – 24.79
[Overall]; Combination Therapy + Ixazomib Therapy12.438.86 – 24.79
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) Secondary · 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)

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 sca

Baseline
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy44.44± 40.369
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy63.25± 24.085
[Overall]; Combination Therapy + Ixazomib Therapy60.74± 26.981
Cycle 23
GroupValue95% CI
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy0± NA
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy54.17± 8.740
[Overall]; Combination Therapy + Ixazomib Therapy46.43± 21.973
Cycle 32
GroupValue95% CI
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy50.00± 23.750
[Overall]; Combination Therapy + Ixazomib Therapy50.00± 23.750

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 39 months as a maximum. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy
Serious: 3/6 (50%)
Deaths: 0/6
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy
Serious: 14/39 (36%)
Deaths: 2/39
[Overall]; Combination Therapy + Ixazomib Therapy
Serious: 17/45 (38%)
Deaths: 2/45

Serious adverse events (18 terms)

ReactionSystem[VRd]; Bortezomib + Lenali…[KRd]; Carfilzomib + Lenal…[Overall]; Combination The…
PneumoniaInfections and infestations
InfluenzaInfections and infestations
Acute kidney injuryRenal and urinary disorders
Febrile neutropeniaBlood and lymphatic system disorders
Prinzmetal anginaCardiac disorders
Duodenal ulcerGastrointestinal disorders
EnterocolitisGastrointestinal disorders
PyrexiaGeneral disorders
Bile duct stoneHepatobiliary disorders
GastroenteritisInfections and infestations
Pneumonia bacterialInfections and infestations
Compression fractureInjury, poisoning and procedural complications
Spinal compression fractureInjury, poisoning and procedural complications
Tibia fractureInjury, poisoning and procedural complications
Tumour lysis syndromeMetabolism and nutrition disorders
Bone painMusculoskeletal and connective tissue disorders
Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Other adverse events (12 terms — click to expand)

ReactionSystem[VRd]; Bortezomib + Lenali…[KRd]; Carfilzomib + Lenal…[Overall]; Combination The…
DiarrhoeaGastrointestinal disorders
White blood cell count decreasedInvestigations
Platelet count decreasedInvestigations
Neutrophil count decreasedInvestigations
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
MalaiseGeneral disorders
PyrexiaGeneral disorders
NasopharyngitisInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Taste disorderNervous system disorders

Most-reported serious reactions: Pneumonia, Influenza, Acute kidney injury, Febrile neutropenia, Prinzmetal angina, Duodenal ulcer, Enterocolitis, Pyrexia.

Data from ClinicalTrials.gov NCT03416374 adverse events section.

Sponsor's own description

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.

Publications & conference data

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

  1. Ezh2 inhibition in Kras-driven lung cancer amplifies inflammation and associated vulnerabilities.
    Serresi M, Siteur B, Hulsman D, Company C, et al · · 2018 · cited 34× · PMID 30487290 · DOI 10.1084/jem.20180801
  2. The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.
    Paradzik T, Bandini C, Mereu E, Labrador M, et al · · 2021 · cited 28× · PMID 33799793 · DOI 10.3390/cancers13061235
  3. In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management.
    Rifkin RM, Girnius SK, Noga SJ, Birhiray RE, et al · · 2023 · cited 2× · PMID 37726298 · DOI 10.1038/s41408-023-00912-9
  4. Efficacy and Safety of Ixazomib Plus Lenalidomide and Dexamethasone Following Injectable PI-Based Therapy in Relapsed/Refractory Multiple Myeloma.
    Abe Y, Sasaki M, Takezako N, Ito S, et al · · 2023 · cited 1× · PMID 37341778 · DOI 10.1007/s00277-023-05212-7

Verify or expand the search:

Other trials of Ixazomib

Trials testing the same drug.

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Trials by the same sponsor.

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