Isa-VRD in TIE HRMM

NCT ID: NCT07334535

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-30
• Study Completion Date: 2029-01-31

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.

Detailed Description

This is a prospective, multicenter, randomized, open-label, Phase IIIb clinical trial. The study aims to evaluate the efficacy and safety of the quadruplet regimen Isatuximab in combination with Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRD) compared to the standard triplet regimen of Bortezomib, Lenalidomide, and Dexamethasone (VRD) in newly diagnosed high-risk multiple myeloma (HRMM) patients who are not candidates for autologous stem cell transplantation.

A total of 117 participants will be enrolled and randomly assigned in a 2:1 ratio to receive either Isa-VRD (78 participants) or VRD (39 participants). The study consists of an induction-consolidation phase (cycles 1-12) followed by a maintenance phase (from cycle 13 onwards until disease progression or unacceptable toxicity).

The primary endpoint is the rate of minimal residual disease (MRD) negativity in the bone marrow assessed by flow cytometry at 12 months of treatment. Key secondary endpoints include MRD negativity rate at 18 months, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IsaVRD group

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.

Group Type: EXPERIMENTAL

Isatuximab, bortezomib, lenalidomide, dexamethason

Intervention Type: DRUG

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.

VRD group

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.

Group Type: ACTIVE_COMPARATOR

Bortezomib, Lenalidomide, Dexamethasone

Intervention Type: DRUG

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.

Interventions

Isatuximab, bortezomib, lenalidomide, dexamethason

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.

Intervention Type: DRUG

Bortezomib, Lenalidomide, Dexamethasone

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Handan Central Hospital

OTHER

Sponsor Role: collaborator

Inner Mongolia People's Hospital

OTHER

Sponsor Role: collaborator

The Affiliated Hospital of Qingdao University

OTHER

Sponsor Role: collaborator

Hebei Medical University Third Hospital

OTHER

Sponsor Role: collaborator

North China University of Science and Technology

OTHER

Sponsor Role: collaborator

China-Japan Union Hospital, Jilin University

OTHER

Sponsor Role: collaborator

Cangzhou Central Hospital

OTHER

Sponsor Role: collaborator

Yantai Yuhuangding Hospital

OTHER

Sponsor Role: collaborator

Shengjing Hospital

OTHER

Sponsor Role: collaborator

Second Hospital of Shanxi Medical University

OTHER

Sponsor Role: collaborator

Beijing Chao Yang Hospital

OTHER

Sponsor Role: collaborator

Beijing Jishuitan Hospital

OTHER

Sponsor Role: collaborator

Henan Cancer Hospital

OTHER_GOV

Sponsor Role: collaborator

Beijing Hospital

OTHER_GOV

Sponsor Role: collaborator

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: collaborator

Shandong Cancer Hospital and Institute

OTHER

Sponsor Role: collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Junling Zhuang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Junling Zhuang

Role: STUDY_CHAIR

Peking Union Medical College, department of hematology

Locations

Junling Zhuang

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Zhuang Junling, PhD.MD

Role: CONTACT

zhuangjunling@pumch.cn

+86 13910118511

Fujing Zhang, MD.

Role: CONTACT

+86 15701569090

Facility Contacts

Junling Zhuang

Role: primary

zhuangjunling@pumch.cn

+8613910118511

References

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.

Reference Type: BACKGROUND

PMID: 35653112 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38832972 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38830994 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24987056 (View on PubMed)

Other Identifiers

2025-PUMCH-C-040

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

K9520

Identifier Type: -

Identifier Source: org_study_id