Isa-VRD in TIE HRMM

January 11, 2026 updated by: Junling Zhuang, Peking Union Medical College Hospital

A Prospective, Randomized, Multi-center Study Comparing Isatuximab in Combination With VRD Versus VRD in High-Risk, Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma.

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

117

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Fujing Zhang, MD.
  • Phone Number: +86 15701569090

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100730

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Active Comparator: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MRD negativity rate at 12 months
Time Frame: at 12 months post-treatment initiation
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
MRD negativity rate at 18 months
Time Frame: at 18 months post-treatment initiation
MRD negativity rate at 18 months post-treatment initiation, assessed by EuroFlow (NGF) with a sensitivity of at least 10-5
at 18 months post-treatment initiation
Progression-free survival
Time Frame: From date of enrollment until the date of first documented progression
from enrollment to first disease progression
From date of enrollment until the date of first documented progression
overall survival
Time Frame: : From date of enrollment until the date of death from any cause
from enrollment to death with follow-up
: From date of enrollment until the date of death from any cause
Overall response rate
Time Frame: From randomization until the end of the induction-consolidation phase
The proportion of participants who achieve a predefined response or better according to the International Myeloma Working Group (IMWG) uniform response criteria. The response categories included in the ORR calculation are: stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR). ORR will be calculated as (number of participants with sCR+CR+VGPR+PR) / (total number of response-evaluable participants) * 100%.
From randomization until the end of the induction-consolidation phase

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Henan Cancer Hospital
Shengjing Hospital
The Affiliated Hospital of Qingdao University
Xuanwu Hospital, Beijing
Beijing Chao Yang Hospital
Beijing Hospital
Shandong Cancer Hospital and Institute
Hebei Medical University Third Hospital
Cangzhou Central Hospital
Beijing Jishuitan Hospital
China-Japan Union Hospital, Jilin University
Second Hospital of Shanxi Medical University
Inner Mongolia People's Hospital
Yantai Yuhuangding Hospital
Handan Central Hospital
North China University of Science and Technology

Investigators

  • Study Chair: Junling Zhuang, Peking Union Medical College, department of hematology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 30, 2026

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

January 3, 2026

First Submitted That Met QC Criteria

January 3, 2026

First Posted (Estimated)

January 12, 2026

Study Record Updates

Last Update Posted (Actual)

January 13, 2026

Last Update Submitted That Met QC Criteria

January 11, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • K9520
  • 2025-PUMCH-C-040 (Other Grant/Funding Number: National High Level Hospital Clinical Research)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing Time Frame

After publication, the data will become available

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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