MRD-Adaptive Guided Immunotherapy With CAR-T for Transplant-Ineligible Patients With Multiple Myeloma

NCT07106736 | Recruiting Phase 2

• 1 other identifier: IIT2025064
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, clinical study to evaluate the efficacy and safety of a fully immunotherapy-based strategy guided by MRD-driven dynamic risk stratification in transplant-ineligible patients with newly diagnosed multiple myeloma.

Conditions

Multiple Myeloma, Newly Diagnosed

Keywords

Multiple myeloma; MRD; CAR-T; BiTEs

Outcome Measures

Primary Outcomes (2)

• Sustained MRD-negative rate

  Rate of patients achieving sustained MRD negativity for more than 12 months

  Up to 2 year

• Progression free survival (PFS)

  Progression free survival is defined as the time from the date of diagnosis to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first

  Up to 3 year

Secondary Outcomes (3)

• Complete response rate (CRR)

  Up to 2 years

• MRD negativity rate

  Up to 2 years

• Overall survival (OS)

  Up to 5 year

Study Arms (2)

Standard-risk

EXPERIMENTAL

Enrolled patients will be stratified into standard-risk group based on the absence of ultra-high-risk features, defined as: (1) double-hit cytogenetics, (2) presence of extramedullary disease, or (3) circulating tumor cells (CTCs) ≥2%. Patients in the standard-risk group will receive BCMA CAR-T therapy after standard induction, followed by standard consolidation and maintenance. Patients achieving sustained MRD negativity and stringent complete response (sCR) on two consecutive assessments may enter a treatment-free observation phase. Patients who experience MRD resurgence or loss of response will resume maintenance therapy.

Biological: BCMA CAR-T

Ultra high risk

EXPERIMENTAL

Enrolled patients will be stratified into an ultra-high-risk group based on the presence of ultra-high-risk features, defined as: (1) double-hit cytogenetics, (2) presence of extramedullary disease, or (3) circulating tumor cells (CTCs) ≥2%. Patients in the ultra-high-risk group will also receive BCMA CAR-T therapy after induction, followed by GPRC5D/CD3 bispecific antibody consolidation and maintenance. Patients achieving sCR and sustained MRD negativity (≥12 months) may enter treatment-free observation, while those with MRD resurgence or loss of response will resume maintenance therapy.

Biological: BCMA CAR-T; Drug: GPRC5D/CD3 BiTEs

Interventions

BCMA CAR-T BIOLOGICAL

Patients will receive single-dose infusion of autologous BCMA-directed CAR-T cellsBCMA CAR-T single dose (3.0 x 10\^6 cells /kg).

Standard-risk; Ultra high risk

GPRC5D/CD3 BiTEs DRUG

Patients will receive GPRC5D/CD3 BiTEs maintenance therapy at a dose of 54 μg/kg every 4 weeks, starting 3 months after BCMA CAR-T infusion.

Ultra high risk

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤ 75 years.
• Participants with documented newly-diagnosed multiple myeloma according to IMWG diagnostic criteria.
• Measurable disease at screening, defined as: Serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
• Patients deemed ineligible for high-dose chemotherapy with ASCT due to any of the following: Age ≥65 years; Investigator assessment of ineligibility; ECOG performance status 3-4; Repeated failure of hematopoietic stem cell mobilization; Patient's decision to defer ASCT.
• Tumor cells were BCMA and GPRC5D positive.
• Serum total bilirubin \<2 x upper limit of normal (ULN), serum AST and ALT \<3 x ULN, creatinine clearance ≥ 30mL/min (Cockroft-Gault formula).
• Informed Consent/Assent: All subjects have the ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Active amyloidosis.
• Central nervous system involvement.
• Prior BCMA-targeted therapy or CAR-T therapy.
• Active hepatitis B or hepatitis C virus infection.
• Known HIV infection.
• Life expectancy \<6 months.
• Woman who are pregnant or breastfeeding.
• Evidence of uncontrolled dysfunction of heart, lung, brain, and other important organs.
• Any other conditions that are not eligible for the trial in the judgement of the principal investigator.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Bites and Stings

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Central Study Contacts

Gang An, PhD&MD

CONTACT

86-022-23909171; angang@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 6, 2025
• Study Start: August 10, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)