NCT07334535

Brief Summary

This is a multicenter, prospective, randomized controlled trial designed to compare the quadruplet regimen of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRD) with the standard triplet regimen (VRD) in newly diagnosed, transplant-ineligible patients with high-risk multiple myeloma (HRMM). Primary Hypothesis: The addition of isatuximab to VRD will significantly improve the MRD negativity rate at 12 months compared to VRD alone in HR-NDMM patients. Secondary Hypotheses: Isa-VRD will lead to higher overall response rates (ORR), deeper responses, and improved progression-free survival (PFS) and overall survival (OS). The safety profile of Isa-VRD will be manageable and consistent with the known safety profiles of its individual components.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
117

participants targeted

Target at P50-P75 for phase_4 multiple-myeloma

Timeline
31mo left

Started Jan 2026

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress13%
Jan 2026Jan 2029

First Submitted

Initial submission to the registry

January 3, 2026

Completed
9 days until next milestone

First Posted

Study publicly available on registry

January 12, 2026

Completed
18 days until next milestone

Study Start

First participant enrolled

January 30, 2026

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2029

Last Updated

January 13, 2026

Status Verified

January 1, 2026

Enrollment Period

2.4 years

First QC Date

January 3, 2026

Last Update Submit

January 11, 2026

Conditions

Multiple Myeloma

Keywords

multiple myelomaisatuximabRCT

Outcome Measures

Primary Outcomes (1)

  • MRD negativity rate at 12 months

    MRD negativity rate at 12 months post-treatment initiation, assessed by EuroFlow (NGF) with a sensitivity of at least 10-5

    at 12 months post-treatment initiation

Secondary Outcomes (4)

  • MRD negativity rate at 18 months

    at 18 months post-treatment initiation

  • Progression-free survival

    From date of enrollment until the date of first documented progression

  • overall survival

    : From date of enrollment until the date of death from any cause

  • Overall response rate

    From randomization until the end of the induction-consolidation phase

Study Arms (2)

IsaVRD group

EXPERIMENTAL

Participants in this group will receive the quadruplet induction-consolidation regimen of Isatuximab in combination with Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRD) for 12 cycles (each cycle is 28 days). This will be followed by a maintenance therapy with Isatuximab, Bortezomib and Lenalidomide until disease progression or unacceptable toxicity.

Drug: Isatuximab, bortezomib, lenalidomide, dexamethason

VRD group

ACTIVE COMPARATOR

Participants in this group will receive the standard triplet induction-consolidation regimen of Bortezomib, Lenalidomide, and Dexamethasone (VRD) for 12 cycles (each cycle is 28 days). This will be followed by a maintenance therapy with Bortezomib and Lenalidomide until disease progression or unacceptable toxicity.

Drug: Bortezomib, Lenalidomide, Dexamethasone

Interventions

Isatuximab, bortezomib, lenalidomide, dexamethasonDRUG

Participants in this group will receive the quadruplet induction-consolidation regimen of Isatuximab in combination with Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRD) for 12 cycles (each cycle is 28 days). This will be followed by a maintenance therapy with Isatuximab, Bortezomib and Lenalidomide until disease progression or unacceptable toxicity.

IsaVRD group
Bortezomib, Lenalidomide, DexamethasoneDRUG

Participants in this group will receive the standard triplet induction-consolidation regimen of Bortezomib, Lenalidomide, and Dexamethasone (VRD) for 12 cycles (each cycle is 28 days). This will be followed by a maintenance therapy with Bortezomib and Lenalidomide until disease progression or unacceptable toxicity.

VRD group

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Newly diagnosed Multiple myeloma ，meeting the IMWG 2025 definition of high-risk MM (any one criterion):
  • (1) Del(17p) (\>20% of plasma cells) and/orTP53 mutation or（2）One of these translocations cooccurring with 1q+ and/or del(1p32) , or t(4;14), or t(14;16), or t(14;20) or （3） Monoallelic del(1p32) along with 1q+ or biallelic del(1p32) or（4） High β2M (\>5.5 mg/dL) with normal creatinine (\<1.2 mg/dL) or（5）Or presents with any other high-risk feature: meeting diagnostic criteria for primary plasma cell leukemia or presence of extramedullary plasmacytoma at baseline;
  • Age ≥18 years and ≤80 years;
  • Not eligible for autologous hematopoietic stem cell transplantation or has declined transplantation for other reasons.
  • ECOG score 0-2
  • Expected survival time \> 3 months
  • Sufficient organ function is defined as follows: absolute neutrophil count ≥ 1.0×10\^9/L, platelet count ≥ 50×10\^9/L (when the proportion of bone marrow plasma cells is \<50%), hemoglobin ≥ 7.5 g/dL; total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the upper limit of normal; creatinine clearance rate ≥ 30 mL/min; left ventricular ejection fraction ≥ 50%.
  • Fertile female or male subjects must agree to take effective contraceptive measures during the study period and within the specified time after the last administration.
  • Voluntarily participated in this study, signed the informed consent form, had good compliance, and was cooperative during the follow-up.

You may not qualify if:

  • Prior systemic anti-myeloma therapy;
  • Viral infections including HBV, HCV, HIV, etc.;
  • Serious cardiovascular and cerebrovascular diseases, such as: within 6 months before screening, myocardial infarction, unstable angina pectoris, severe arrhythmia, New York Heart Function Classification III-IV grade, or left ventricular ejection fraction \<50%.
  • Severe neurological or mental disorders that affect the ability to give informed consent or comply with the protocol.
  • Had an allergic reaction to isatuximab, bortezomib, lenalidomide, dexamethasone or any excipients
  • Pregnant or lactating women.
  • Participated in other interventional clinical studies, or had received other anti-tumor treatments within the specified time before the first administration of this study.
  • The researcher believes that there are any other circumstances unsuitable for participating in this study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Junling Zhuang

Beijing, Beijing Municipality, 100730, China

Location

Related Publications (4)

  • Davies FE, Pawlyn C, Usmani SZ, San-Miguel JF, Einsele H, Boyle EM, Corre J, Auclair D, Cho HJ, Lonial S, Sonneveld P, Stewart AK, Bergsagel PL, Kaiser MF, Weisel K, Keats JJ, Mikhael JR, Morgan KE, Ghobrial IM, Orlowski RZ, Landgren CO, Gay F, Caers J, Chng WJ, Chari A, Walker BA, Kumar SK, Costa LJ, Anderson KC, Morgan GJ. Perspectives on the Risk-Stratified Treatment of Multiple Myeloma. Blood Cancer Discov. 2022 Jul 6;3(4):273-284. doi: 10.1158/2643-3230.BCD-21-0205.

    PMID: 35653112BACKGROUND

  • Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hajek R, Liu Z, Minarik J, Moreau P, Romejko-Jarosinska J, Spicka I, Vorobyev VI, Besemer B, Ishida T, Janowski W, Kalayoglu-Besisik S, Parmar G, Robak P, Zamagni E, Goldschmidt H, Martin TG, Manier S, Mohty M, Oprea C, Bregeault MF, Mace S, Berthou C, Bregman D, Klippel Z, Orlowski RZ; IMROZ Study Group. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Oct 31;391(17):1597-1609. doi: 10.1056/NEJMoa2400712. Epub 2024 Jun 3.

    PMID: 38832972BACKGROUND

  • Leleu X, Hulin C, Lambert J, Bobin A, Perrot A, Karlin L, Roussel M, Montes L, Cherel B, Chalopin T, Slama B, Chretien ML, Laribi K, Dingremont C, Roul C, Mariette C, Rigaudeau S, Calmettes C, Dib M, Tiab M, Vincent L, Delaunay J, Santagostino A, Macro M, Bourgeois E, Orsini-Piocelle F, Gay J, Bareau B, Bigot N, Vergez F, Lebreton P, Tabrizi R, Waultier-Rascalou A, Frenzel L, Le Calloch R, Chalayer E, Braun T, Lachenal F, Corm S, Kennel C, Belkhir R, Blade JS, Joly B, Richez-Olivier V, Gardeney H, Demarquette H, Robu-Cretu D, Garderet L, Newinger-Porte M, Kasmi A, Royer B, Decaux O, Arnulf B, Belhadj K, Touzeau C, Mohty M, Manier S, Moreau P, Avet-Loiseau H, Corre J, Facon T. Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial. Nat Med. 2024 Aug;30(8):2235-2241. doi: 10.1038/s41591-024-03050-2. Epub 2024 Jun 3.

    PMID: 38830994BACKGROUND

  • Deckert J, Wetzel MC, Bartle LM, Skaletskaya A, Goldmacher VS, Vallee F, Zhou-Liu Q, Ferrari P, Pouzieux S, Lahoute C, Dumontet C, Plesa A, Chiron M, Lejeune P, Chittenden T, Park PU, Blanc V. SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin Cancer Res. 2014 Sep 1;20(17):4574-83. doi: 10.1158/1078-0432.CCR-14-0695. Epub 2014 Jul 1.

    PMID: 24987056BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximabBortezomibLenalidomideDexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Boronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsOrganic ChemicalsPyrazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsPiperidonesPiperidinesIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Study Officials

  • Junling Zhuang

    Peking Union Medical College, department of hematology

    STUDY CHAIR

Central Study Contacts

Zhuang Junling, PhD.MD

CONTACT

+86 13910118511zhuangjunling@pumch.cn

Fujing Zhang, MD.

CONTACT

+86 15701569090

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

January 3, 2026

First Posted

January 12, 2026

Study Start

January 30, 2026

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

January 1, 2029

Last Updated

January 13, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

individual baseline characteristic, treatment and follow-up results will be shared after publication

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
After publication, the data will become available

Locations

CN(1)