Recipient organisationNIHR Nottingham Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodJan 2025 — Sept 2027
In plain English
AI plain-English summary
A clinical trial is testing whether a two-drug combination can stop a precancerous blood condition from turning into full-blown multiple myeloma. The condition, called high-risk smouldering myeloma, sits in a grey zone: patients have abnormal plasma cells in their bone marrow but no symptoms of active cancer. Currently, doctors watch and wait until the disease progresses. This trial aims to intervene earlier, using the drugs iberdomide and isatuximab to kill or suppress the abnormal cells before they cause organ damage. The study will also track why some patients decline to participate, addressing a real-world gap in trial design. If the treatment proves safe and effective, it could shift the standard of care from passive monitoring to active prevention for this high-risk group. That would mean fewer patients developing the painful bone lesions, kidney failure, and anaemia that define active myeloma. The trial also includes extensive biological analysis—genomics, immune profiling, and bone marrow organoids—to understand why some patients respond and others do not, which could guide future therapies.
View original technical description
The overall aims of the study are: •To determine if the combination of iberdomide and isatuximab with dexamethasone is safe and well tolerated •To determine if the treatment is efficacious in inducing disease response in high-risk smouldering myeloma,thus preventing the development of active multiple myeloma The primary endpoints are: •Treatment deliverability,measured by treatment discontinuation before completion of 26 cycles •Efficacy measured by best overall response rate =by the end of treatment The secondary endpoints are: •Progression Free Survival •Time to biochemical progression •Progression Free Survival 2 •Best overall response to subsequent line of therapy •Overall Survival •Minimal Residual Disease negativity rates •Very Good Partial Response and Complete Response + Minimal Residual Disease negative rates •Adverse Event and Adverse Device Effect rates •Median and cumulative doses of Iberdomide and Isatuximab •Treatment compliance (including study drugs and device deficiencies) •Patient Reported Outcome Measures The translational biological and exploratory studies include: •Immune phenotype and function,including T-cells,natural killer cells and myeloid cells,T cell receptor sequence and clonality,cytokines in serum.•Tumour genomics. Genomic structural variants,short nucleotide variants,epigenetic modifications and expression changes at baseline and on therapy. Subclonal architecture,neo-antigen burden,transcriptional profile pre and post-therapy. •Examination of stromal elements including bone forming and resorbing cells. •Spatial analysis of tumour and non-tumour cells in bone marrow and effect of therapy. •Establish organoids from bone marrow cells to study effect of treatment.•Proteomic,cell-free DNA and circulating tumour cells analysis in blood samples. •Genomic,cytogenetic and immune features correlation with response to treatment and risk of progression (defined as biochemical progression). •Comparisons will be made with the matched untreated patients in the observational cohort study COSMOS.•Compare clinical outcomes and translational data with results obtained in the phase 2 study comparing iberdomide vs iberdomide/dexamethasone to treat high risk smouldering myeloma(NCT04776395). •Describe reasons why eligible patients choose not to take part in the study.
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