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

Phase 2RecruitingNCT07106736

Institute of Hematology & Blood Diseases Hospital, China60 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma, Newly Diagnosed

Interventions

BCMA CAR-TBIOLOGICAL

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 BiTEsDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (1)

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

Tianjin, Tianjin Municipality, China

RECRUITING

Outcomes

Primary Outcomes

Sustained MRD-negative rate

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

Time frame: 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

Time frame: Up to 3 year

Secondary Outcomes

Complete response rate (CRR)

CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response accoording to the IMWG criteria.

Time frame: Up to 2 years

MRD negativity rate

Rate of patients achieving MRD negativity

Time frame: Up to 2 years

Overall survival (OS)

Overall survival is defined as the time from the date of diagnosis to the date of death due to any cause

Time frame: Up to 5 year

Central Contacts

Gang An, PhD&MD

CONTACT

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

Data from ClinicalTrials.gov

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