Phase 3
Completed N=302
Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients
Plasma Cell Myeloma
Source: ClinicalTrials.gov NCT03275285 ↗
Enrolled (actual)
302
Serious AEs
67.9%
Results posted
Feb 2023
Primary outcomePrimary: Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis — 19.15; NA months — p=0.0007
◆ Published Evidence
Highly cited
378citations · ~76 / year
Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.
Summary
The purpose of this study it to compare the efficacity of isatuximab when combined to carfilzomib and dexamethasone versus carfilzomib and dexamethasone in patients with multiple myeloma already treated with 1 to 3 prior lines of therapy.
Linked Publications (5)
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Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.
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Anti-CD38 monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping.
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Isatuximab Plus Carfilzomib and Dexamethasone Versus Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: IKEMA Subgroup Analysis by Prior Transplantation.
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Isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma (IKEMA): overall survival analysis of a phase 3, randomised, controlled trial.
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Isatuximab-Specific Immunofixation Electrophoresis Assay to Remove Interference in Serum M-Protein Measurement in Patients with Multiple Myeloma.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis |
19.15; NA | 0.0007 sig |
| PRIMARY Progression Free Survival as Determined by Independent Response Committee: [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Primary Analysis |
20.27; NA | 0.0016 sig |
| PRIMARY Progression Free Survival as Determined by Independent Response Committee: Final Analysis |
19.15; 35.65 | — |
| PRIMARY Progression Free Survival as Determined by Independent Response Committee [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Final Analysis |
20.76; 41.66 | — |
| SECONDARY Percentage of Participants With Overall Response (OR) as Determined by Independent Response Committee: Primary Analysis |
82.9; 86.6 | 0.1930 |
| SECONDARY Percentage of Participants With Very Good Partial Response (VGPR) or Better as Determined by Independent Response Committee: Primary Analysis |
56.1; 72.6 | — |
| SECONDARY Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Primary Analysis |
13.0; 29.6 | — |
| SECONDARY Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Final Analysis |
13.8; 33.5 | — |
| SECONDARY Percentage of Participants With Complete Response (CR) as Per Independent Response Committee: Final Analysis |
28.5; 44.1 | — |
| SECONDARY Percentage of Participants With Complete Response With MRD Negativity: Final Analysis |
12.2; 26.3 | — |
| SECONDARY Overall Survival (OS) |
50.60; NA | — |
| SECONDARY Duration of Response (DOR): Primary Analysis |
NA; NA | — |
| SECONDARY Time to Progression (TTP): Primary Analysis |
20.27; NA | — |
| SECONDARY Time to First Response: Primary Analysis |
1.12; 1.08 | — |
| SECONDARY Time to Best Response: Primary Analysis |
3.78; 4.60 | — |
| SECONDARY Second Progression Free Survival (PFS2): Final Analysis - Data Cut-off Date of 14 Jan 2022 |
35.58; 47.18 | — |
| SECONDARY Second Progression Free Survival (PFS2): Overal Survival Analysis - Data Cut-off Date of 07 Feb 2023 |
32.36; 47.18 | — |
| SECONDARY Number of Participants With Renal Response (RR): Primary Analysis |
4; 13; 1; 4 | — |
| SECONDARY Health Related Quality of Life (HRQL): Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status Score at Specified Timepoints |
1.52; -1.60; 4.17; 0.05; 3.58; -1.89 | — |
| SECONDARY HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score at Specified Timepoints: Primary Analysis |
-5.34; -3.40; -8.28; -7.42; -5.45; -7.46 | — |
| SECONDARY HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment at Specified Timepoints: Primary Analysis |
1.23; 1.41; 0.44; 0.84; 0.83; 0.99 | — |
| SECONDARY HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Body Image Score at Specified Timepoints: Primary Analysis |
-1.29; -1.27; 1.98; 1.27; -1.65; -1.10 | — |
| SECONDARY HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Future Perspective at Specified Timepoints: Primary Analysis |
0.54; 7.57; 4.84; 9.70; 6.60; 8.55 | — |
| SECONDARY HRQL: Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints: Primary Analysis |
0.05; 0.04; 0.06; 0.05; 0.02; 0.05 | — |
| SECONDARY HRQL: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints: Primary Analysis |
2.42; 0.60; 4.70; 3.47; 6.03; 2.29 | — |
| SECONDARY Pharmacokinetics: Plasma Concentration at End of Infusion (Ceoi) of Isatuximab: Primary Analysis |
274.01; 380.28; 522.74 | — |
| SECONDARY Pharmacokinetics: Plasma Concentration of Isatuximab at Ctrough: Primary Analysis |
3.66; 82.14; 180.02; 252.63; 324.28; 295.78 | — |
| SECONDARY Pharmacokinetics: Maximum Observed Concentration (Cmax) of Carfilzomib: Primary Analysis |
2090 | — |
| SECONDARY Pharmacokinetics: Clast of Carfilzomib: Primary Analysis |
3.00 | — |
| SECONDARY Pharmacokinetics: Tmax of Carfilzomib: Primary Analysis |
0.54 | — |
| SECONDARY Pharmacokinetics: Tlast of Carfilzomib: Primary Analysis |
4.50 | — |
| SECONDARY Pharmacokinetics: Area Under the Plasma Concentration Time Curve (AUC) of Carfilzomib: Primary Analysis |
784 | — |
| SECONDARY Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time 0 to Last Quantifiable Concentration (AUClast) of Carfilzomib: Primary Analysis |
779 | — |
| SECONDARY Pharmacokinetics: Percentage of Extrapolation of AUC (AUCext) of Carfilzomib: Primary Analysis |
— | — |
| SECONDARY Pharmacokinetics: Terminal Half-life (t1/2z) of Carfilzomib: Primary Analysis |
0.860 | — |
| SECONDARY Pharmacokinetics: Clearance at Steady State (CLss) of Carfilzomib: Primary Analysis |
466 | — |
| SECONDARY Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Carfilzomib: Primary Analysis |
453 | — |
| SECONDARY Number of Participants With Anti-Drug Antibodies (ADA): Primary Analysis |
0; 0; 0 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs): LPLV Analysis |
119; 175; 74; 129 | — |
Eligibility Criteria
Inclusion criteria
- Participants with MM previously treated with prior 1 to 3 lines and with measurable serum M-protein (>= 0.5 gram/deciliter) and/or urine M-protein (>= 200 milligram/24 hours).
Exclusion criteria
- Participants previously pretreated with carfilzomib, who never achieved at least one minor response during previous therapies and/or last previous therapy completed within 14 last days.
- Participants with serum free light chain (FLC) measurable disease only.
- Participants less than 18 years old, participants with Eastern Cooperative Oncology Group performance status more than 2.
- Participants with inadequate biological tests.
- Participants with myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association class III or IV congestive heart failure, superior or equal to grade 3 arrhythmias, stroke or transient ischemic attack within last 6 months, and/or left ventricular ejection fraction lower than 40%.
- Participants with previous cancer unless disease free for more than 5 years or in situ cancer curatively treated.
- Participants with known acquired immunodeficiency syndrome related illness or human immunodeficiency virus requiring antiretroviral treatment, or hepatitis A, B, or C active infection.
- Women of childbearing potential or male participant with women of childbearing potential who do not agree to use highly effective method of birth control.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Data sourced from ClinicalTrials.gov (NCT03275285) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.