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

NCT ID: NCT07106736

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-10
• Study Completion Date: 2029-08-01

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.

Detailed Description

All subjects will receive standard induction therapy for up to four cycles prior to screening. Following response evaluation, those who meet the inclusion criteria will be enrolled and subsequently stratified into standard-risk and ultra-high-risk groups based on predefined clinical and molecular features.

Patients in the standard-risk group will receive BCMA CAR-T therapy, 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 in the ultra-high-risk group will also receive BCMA CAR-T therapy, followed by GPRC5D/CD3 bispecific antibody consolidation and maintenance. Patients achieving sCR and sustained MRD negativity (≥12 months) may enter treatment-free observation. Patients who experience MRD resurgence or loss of response will resume maintenance therapy.

Conditions

Multiple Myeloma, Newly Diagnosed

Study Design

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

Study Groups

Standard-risk

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.

Group Type: EXPERIMENTAL

BCMA CAR-T

Intervention Type: 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).

Ultra high risk

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.

Group Type: EXPERIMENTAL

BCMA CAR-T

Intervention Type: 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).

GPRC5D/CD3 BiTEs

Intervention Type: 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.

Interventions

BCMA CAR-T

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

Intervention Type: BIOLOGICAL

GPRC5D/CD3 BiTEs

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years and ≤ 75 years.

2. Participants with documented newly-diagnosed multiple myeloma according to IMWG diagnostic criteria.

3. 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.

4. 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.

5. Tumor cells were BCMA and GPRC5D positive.

6. Serum total bilirubin <2 x upper limit of normal (ULN), serum AST and ALT <3 x ULN, creatinine clearance ≥ 30mL/min (Cockroft-Gault formula).

7. Informed Consent/Assent: All subjects have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

1. Active amyloidosis.

2. Central nervous system involvement.

3. Prior BCMA-targeted therapy or CAR-T therapy.

4. Active hepatitis B or hepatitis C virus infection.

5. Known HIV infection.

6. Life expectancy <6 months.

7. Woman who are pregnant or breastfeeding.

8. Evidence of uncontrolled dysfunction of heart, lung, brain, and other important organs.

9. Any other conditions that are not eligible for the trial in the judgement of the principal investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Gang An, PhD&MD

Role: CONTACT

angang@ihcams.ac.cn

86-022-23909171

Facility Contacts

Gang An

Role: primary

angang@ihcams.ac.cn

86-022-23909171

Other Identifiers

IIT2025064

Identifier Type: -

Identifier Source: org_study_id