Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Relapsed or Refractory Multiple Myeloma

A Single-Arm, Single-Center Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Relapsed or Refractory Multiple Myeloma

This is a single arm, single center clinical study evaluating the safety and efficacy of CAR-T treatment for relapsed or refractory multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Biological: BCMA/GPRC5D dual CAR-T

Detailed Description

This study is a single arm, single center study targeting patients with relapsed or refractory multiple myeloma (r/rMM). The study plans to enroll 40 subjects, with a sample size based on actual occurrence and a dosage of 3×10^6/kg±20%~1×10^7/kg ±20% CAR positive T cells.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Qianhai Shekou Free Trade Zone Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Patients or their guardians understand and voluntarily sign an informed consent form and are expected to complete the follow-up examinations and treatments related to the study.
• 2. Aged 18-75 years, any gender.
• 3. Diagnosed with multiple myeloma according to IMWG diagnostic criteria.

• 4. Documented evidence that the patient's multiple myeloma is refractory or relapsed, defined as:

  • a) Refractory: No response to salvage therapy (no response defined as no achievement of minimal response [MR] or disease progression during treatment), or disease progression within 60 days of the last treatment, or patients who achieved MR or higher but experienced disease progression.
  • b) Relapsed: No response to any treatment, including no achievement of MR or higher in any prior treatment, but with minimal changes in M-protein without clinical progression or relapse as per the progression definition.
• 5. Measurable disease at screening based on any of the following criteria: serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours, or diagnosed with light-chain multiple myeloma in the absence of measurable disease in serum or urine: serum immunoglobulin free light chain ≥10 mg/dL and an abnormal κ/γ free light chain ratio, extramedullary measurable lesions, or presence of tumor cells in bone marrow biopsy.
• 6. Patients have recovered from toxicity of prior treatment, with CTCAE toxicity grade ≤2 (unless the abnormality is related to the tumor or is deemed stable by the investigator with no significant impact on safety or efficacy).
• 7. ECOG performance status score of 0-2 and an expected survival of more than 3 months.

• 8. Adequate organ function, including:

  • ALT (alanine transaminase) ≤3 times the upper limit of normal (ULN).
  • AST (aspartate transaminase) ≤3 times ULN.
  • Total bilirubin ≤1.5 times ULN.
  • Serum creatinine ≤1.5 times ULN or creatinine clearance ≥30 mL/min (calculated by Cockcroft-Gault formula).
  • Oxygen saturation ≥92%.
  • Left ventricular ejection fraction (LVEF) ≥45%, confirmed by echocardiography with no evidence of pericardial effusion and no clinically significant electrocardiographic findings.
  • No clinically significant pleural effusion.
• 9. Establishing a required venous access for collection without any leukapheresis contraindications.

Exclusion Criteria:

• 1. Diagnosis or treatment of invasive malignancies other than multiple myeloma within 3 years, unless the malignancy has been curatively treated and there is no known active disease within 3 years before enrollment, or unless the patient has been fully treated for non-melanoma skin cancer with no evidence of disease.
• 2. Prior treatment with the following anti-cancer therapies (before leukapheresis for CAR-T cell production): received targeted therapy, epigenetic therapy, or investigational drug treatment within 14 days or at least 5 half-lives (whichever is shorter); received monoclonal antibody therapy within 21 days; received proteasome inhibitor therapy within 14 days; received immunomodulatory drug therapy within 7 days; received radiation therapy within 14 days (excluding bone marrow radiation ≤5% of bone marrow reserve).
• 3. Underwent hematopoietic stem cell transplantation within 2 months prior to screening.
• 4. History of central nervous system disorders.
• 5. Clinical signs of active central nervous system (CNS) involvement or manifestations of multiple myeloma meningeal involvement.
• 6. Diagnosed with Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or primary AL amyloidosis.
• 7. Positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA quantification, positive for hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, cytomegalovirus (CMV) DNA, syphilis test, or Epstein-Barr virus DNA.
• 8. History of severe allergies (defined as Grade 2 or higher reactions) or known hypersensitivity to any active ingredients, excipients, mouse-derived products, or heterologous proteins included in this trial, including the conditioning regimen.
• 9. Severe cardiac diseases, including but not limited to severe arrhythmias, unstable angina, extensive myocardial infarction, New York Heart Association class III or IV heart failure, myocardial infarction within ≤6 months prior to screening, coronary artery bypass grafting (CABG) performed, except for non-vascular vagal syncope or dehydration, severe non-ischemic cardiomyopathy, and resistant hypertension.
• 10. Unstable systemic diseases, as judged by the investigator, including but not limited to severe liver, kidney, or metabolic diseases requiring drug treatment.
• 11. Had acute or chronic graft-versus-host disease (GVHD) within 6 months prior to screening or required immunosuppressive treatment for GVHD.
• 12. Active autoimmune or inflammatory neurological diseases (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis) and clinically significant active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome) at screening.
• 13. Requires emergency treatment for tumor emergencies at screening (e.g., spinal cord compression, intestinal obstruction, leukostasis, tumor lysis syndrome).
• 14. Has uncontrollable bacterial, fungal, viral, or other infections requiring antibiotic treatment.
• 15. Received blood transfusions or hematopoietic cytokine drugs affecting the patient's blood counts within 2 weeks prior to screening for planned CAR-T cell production, as determined by the investigator to affect cell preparation.

• 16. Receiving steroids or immunosuppressive drugs within 2 weeks of screening for planned CAR-T cell production:

  • a) Steroids: Received systemic corticosteroid treatment within 2 weeks of screening and judged by the investigator to require long-term systemic corticosteroid treatment (excluding inhalation or topical use); and received systemic corticosteroid treatment within 72 hours before cell infusion (excluding inhalation or topical use).
  • b) Immunosuppressive drugs: Receiving immunosuppressive drugs within 2 weeks of screening.
• 17. Underwent major surgery (excluding diagnostic surgery and biopsy) within 4 weeks prior to screening or has unhealed surgical wounds before enrollment.
• 18. Received (attenuated) live virus vaccines within 4 weeks before screening.
• 19. Has severe mental illness.
• 20. History of alcohol abuse or substance abuse.
• 21. Pregnant or lactating women and participants planning to become pregnant within 2 years after cell infusion or their partners planning to become pregnant within 2 years after cell infusion.
• 22. Patients who have contraindications to any study procedure or have other medical conditions that may place them at unacceptable risk according to the investigator 's judgment and/or clinical criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCMA/GPRC5D dual CAR-T; The study plans to enroll 40 subjects, with a sample size based on actual occurrence and a dosage of 3 × 106/kg ± 20%~1 × 107/kg ± 20% CAR positive T cells	Biological: BCMA/GPRC5D dual CAR-T; BCMA/GPRC5D dual CAR-T is a new type CAR-T cells therapy for patients with Relapsed or Refractory Multiple Myeloma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Safety	Count the Incidence of adverse events	Up to 2 years after BCMA/GPRC5D dual CAR-T infusion
Changes in cytokine level	Calculate the change of cytokine level in peripheral blood by flow cytometry after BCMA/GPRC5D dual CAR-T infusion. Cytokines include IL-2、IL-6、IL-10、IFN-γ	Up to 2 years after BCMA/GPRC5D dual CAR-T infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate(CR)	Subjects whose serum and urine immunofixation electrophoresis are negative, and there is no soft tissue plasma cell tumor, with bone marrow plasma cells<5%.	Up to 2 years after BCMA/GPRC5D dual CAR-T infusion
Strict complete response rate(SCR)	Subjects who achieved complete response with normal FLC ratio and confirmed absence of clonal plasma cells in bone marrow by immunohistochemistry.	Up to 2 years after BCMA/GPRC5D dual CAR-T infusion
Very good partial response rate(VGPR)	Subjects who detected serum and urine M protein in immunofixation, but did not detect it from electrophoresis; Or M protein decrease ≥ 90% and urine M protein<100 mg/24h.	Up to 2 years after BCMA/GPRC5D dual CAR-T infusion
Partial response(PR)	Subjects who met the following requirements: （1） A decrease of ≥ 50% in serum M protein and ≥ 90% or<200 mg/24h in urine M protein;; （2） If M protein in serum and urine cannot be detected, it is required to reduce the difference between affected and unaffected serum FLC by ≥ 50%;; （3） If M protein and serum FLC in serum and urine cannot be measured, and the baseline bone marrow plasma cell ratio is ≥ 30%, a reduction of ≥ 50% in the number of bone marrow plasma cells is required;; （4） In addition to the above criteria, if there is a baseline presence of soft tissue plasmacytomas, it is required that the sum of the maximum vertical diameter product (SPD) of the measurable lesion be reduced by ≥ 50%.	Up to 2 years after BCMA/GPRC5D dual CAR-T infusion
Minimal response(MR)	Subjects whose serum M protein decreased by 25%~49% and 24-hour urine M protein decreased by 50%~89%; In addition to the above criteria, if there is a baseline presence of soft tissue plasmocytoma, a measurable reduction in lesion SPD of ≥ 50% is required.	Up to 2 years after BCMA/GPRC5D dual CAR-T infusion
Overall response(OR)	Defined as subjects who achieve sCR, CR, VGPR, and PR.	Up to 2 years after BCMA/GPRC5D dual CAR-T infusion

Collaborators and Investigators

• Sponsor: Guangzhou Bio-gene Technology Co., Ltd
• Collaborators: Shenzhen Qianhai Shekou Free Trade Zone Hospital
• Investigators: Principal Investigator: Yang Xiao, MD, Shenzhen Qianhai Shekou Free Trade Zone Hospital

Publications and helpful links

General Publications

• Wei L, Xiao X, Jing X, Zheng Y, Sun X, Bai W, Li M, Luo M, Xiao Y. Case Report: Summary of multiple CAR-T expansions in anti-BCMA/GPRC5D bispecific CAR-T cell therapy for multiple myeloma. Front Immunol. 2025 Jun 6;16:1607778. doi: 10.3389/fimmu.2025.1607778. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2023
• Primary Completion (Actual): February 2, 2024
• Study Completion (Actual): February 2, 2024

Study Registration Dates

• First Submitted: September 28, 2023
• First Submitted That Met QC Criteria: September 28, 2023
• First Posted (Actual): October 5, 2023

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Myeloma; BCMA; GPRC5D
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Multiple Myeloma
• Other Study ID Numbers: BG-CT-22-008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No