Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma

NCT06762769 | Recruiting Phase 2 DMC

• 1 other identifier: UCL/153707
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 2

Brief Summary

The study will test a new combination of 3 drugs: Isatuximab (Isa), Iberdomide (Iber) and Dexamethasone (Dex), in patients who have intermediate or high risk smouldering myeloma. Smouldering myeloma is an early form of myeloma which may progress to active multiple myeloma, but at a slow rate. Patients with smouldering myeloma do not usually receive any treatment but will have regular check-ups and observation. Some patients have a diagnosis of smouldering myeloma which has a higher risk of progressing to active myeloma. The study will test if the combination of drugs is effective at preventing or delaying the disease progressing into active multiple myeloma. The study will also test if the combination is tolerated and accepted by patients.

Conditions

Smouldering Myeloma

Keywords

Isatuximab; Iberdomide; OBDS; Dexamethasone; MODIFY; Smouldering Myeloma; On Body Delivery System

Outcome Measures

Primary Outcomes (2)

• Treatment deliverability, measured by treatment discontinuation before completion of 26 cycles

  The number and proportion of patients who complete all 26 cycles of trial treatment per protocol (allowing for delays/reductions/omissions deemed acceptable by the protocol) will be presented with two-sided 90% confidence interval. While the sample size is based off of 57 patients being assessable for this endpoint, all eligible patients will be included in the analysis and conclusions will be based on the lower bound of the 90% confidence interval. Patients who do not complete treatment for reasons unrelated to disease or toxicity will be excluded from this analysis (e.g. patient moving away or becoming pregnant), however sensitivity analyses will be performed where these patients are assumed to complete/not complete treatment.

  From the date of registration until the date of treatment completion/discontinuation (approximately 2 years or earlier if patients discontinue treatment early)

• Treatment efficacy measured by best overall response rate by the end of treatment

  The number and proportion of patients who achieve disease response (PR, VGPR, CR or sCR) at any point over the duration of treatment or at the 1 month FU response assessment will be presented with two-sided 90% confidence interval. While the sample size is based off of 53 patients being assessable for this endpoint, all eligible patients will be included in the analysis and conclusions will be based on the lower bound of the 90% confidence interval. All patients who have completed at least one response assessment or stopped protocol treatment early due to toxicity, insufficient response, progression or death will be included in this analysis.

  From the date of registration until the date of 1 month follow up assessment

Secondary Outcomes (14)

• Progression Free Survival

  From the date of registration until the date of first disease progression or death, whichever comes first, assessed up to 5.5 years

• Time to biochemical progression

  from the date of registration until the date of biochemical disease progression, assessed up to 5.5 years

• Progression Free Survival 2

  from the date of registration assessed up to 5.5 years

• Best overall response to subsequent line of therapy

  From the date of registration until the end of follow up, assessed up to 5.5 years

• Overall Survival

  From the date of registration until the date of death, assessed up to 5.5 years

Study Arms (1)

Study treatment

EXPERIMENTAL

All patients will receive 2 years of treatment, over 26 cycles. A cycle is 28 days. The treatment is split into 3 stages. Induction therapy: Cycle 1-4 * Isatuximab is given once a week in cycle 1. Then twice a week in cycle 2-4. It is given subcutaneously using a medical device called an On Body Delivery System * Iberdomide is given on days 1-21. It is given as an oral capsule. * Dexamethasone is given once a week. It is given as an oral tablet. Consolidation therapy: Cycle 5-13 * Isatuximab is given twice a week. * Iberdomide is given on days 1-21 Maintenance therapy: Cycle 14-26 * Isatuximab is given once a month * Iberdomide is given on days 1-21

Drug: Isatuximab; Drug: Iberdomide; Drug: Dexamethasone

Interventions

Isatuximab DRUG

Subcutaneous isatuximab will be delivered using an unlicensed medical device (On Body Delivery System)

Study treatment

Iberdomide DRUG

Oral iberdomide

Study treatment

Dexamethasone DRUG

Oral dexamethasone

Study treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide written informed consent and comply with protocol-mandated visits, treatment plan, laboratory tests and other study procedures.
• Age ≥ 18 years
• Diagnosed with smouldering myeloma (SMM) within 5 years of study registration AND diagnosed with intermediate or high risk SMM within 2 years of registration.:
• i.e. patients may have been diagnosed de novo with intermediate or high risk smouldering myeloma within 2 years of study registration OR
• patients may have been diagnosed with low or low-intermediate smouldering myeloma within 5 years of study registration and then their risk classification has changed to intermediate or high risk within 2 years of study registration.
• Diagnosed with intermediate or high-risk SMM defined by IMWG diagnostic criteria and IMWG SMM risk stratification. Intermediate or high risk is defined by the presence of 2 or more of the following factors:
• BM plasma cell infiltrate \>20%
• Serum paraprotein \>20g/l
• Serum Free Light Chain (SFLC) Ratio \>20 (but \<100)
• Presence of t(4;14), t(14;16), del 17p, del 13q or 1q gain by fluorescence in situ hybridization (FISH) studies. Copy number abnormalities will be considered significant if present in ≥ 20% of cells.
• Measurable disease with at least one of the following:
• Paraprotein ≥5g/L
• Serum free light chains ≥100mg/L with abnormal light chain ratio
• Bence Jones protein ≥200mg/24hr
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

You may not qualify if:

• Multiple Myeloma requiring treatment, as defined by IMWG SLiM-CRAB or CRAB criteria.
• Monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma, primary amyloid light-chain (AL) amyloidosis.
• Low or Low-intermediate risk smouldering myeloma by IMWG criteria
• Received previous treatment for myeloma, smouldering myeloma or solitary plasmacytoma.
• Treatment with any other standard anti-cancer radiotherapy/chemotherapy/targeted therapy including investigational therapy (defined as treatment for which there is currently no regulatory authority approved indication) within 4 weeks prior to registration.
• Rapidly rising paraprotein or serum free light chains, defined as any of the following occurring within the space of 2 months:
• doubling of serum M-protein (minimum rise 5g/l)
• increase of serum M-protein by ≥10 g/L
• increase of involved serum-free light chains (FLC) level by ≥200 mg/L (plus abnormal ratio)
• increase of Bence Jones protein by ≥500mg/24hr
• Corticosteroid treatment with a dose \>10 mg prednisone or equivalent per day within 28 days of initiation of study drugs.
• Unstable angina or myocardial infarction within 4 months prior to registration, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless patient has a pacemaker.
• Prior or concurrent invasive malignancies except the following:
• Adequately treated basal cell or squamous cell skin cancer.
• Incidental finding of low grade (Gleason 3+3 or less) prostate cancer requiring no intervention. (Hormone monotherapy is permitted if overall survival is anticipated to be \>5 years).

Sponsors & Collaborators

• University College, London: lead
• Sanofi: collaborator
• Bristol Myers Squibb Pharmaceuticals Limited: collaborator

Study Sites (2)

Barts Health Trust

London, EC1A 7BE, United Kingdom

RECRUITING

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

RECRUITING

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

isatuximab; iberdomide; Dexamethasone

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

MODIFY Trial Manager

CONTACT

02076799860; ctc.modify@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: January 8, 2025
• Study Start: June 2, 2025
• Primary Completion (Estimated): November 1, 2032
• Study Completion (Estimated): November 1, 2032
• Last Updated: August 1, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)