Safety and Efficacy of Anti-BCMA-GPRC5D CAR-T Cells Therapy in the Treatment of r/r MM

A Clinical Study to Evaluate the Safety and Efficacy of BCMA-GPRC5D CAR-T in Patients With Relapsed/Refractory Multiple Myeloma Who Received Three or More Lines of Therapy

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific BCMA-GPRC5D CAR-T cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Biological: Anti-BCMA-GPRC5D CAR-T cells infusion

Detailed Description

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific BCMA-GPRC5D CAR-T cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.A leukapheresis procedure will be performed to manufacture Anti-BCMA-GPRC5D chimeric antigen receptor (CAR) modified T cells. Prior to Anti-BCMA-GPRC5D CAR-T cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the safety and efficacy of CAR-T therapy was evaluated by investigators.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sanbin Wang, MD
• Study Contact Backup: Name: Sanbin Wang, MD; Phone Number: 13187424131; Email: Sanbin1011@163.com

Study Locations

• China
  • Kunming, Yunnan
    • Kunming, Kunming, Yunnan, China, 650100
      • Recruiting
      • Sanbin Wang
      • Contact: Sanbin Wang, MD; Phone Number: 13187424131; Email: Sanbin1011@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient or his/her guardian understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure;
2. Age 18-75 years old, gender unlimited;
3. Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG);
4. The presence of measurable disease at screening meets one of the following criteria:Serum M-protein ≥ 1.0 g/dL or Urine M-protein ≥ 200 mg/24h or diagnosed as Light-chain MM without measurable disease in serum and urine; Serum free light chain ≥ 10 mg/dL with an abnormal κ/λ ratio;
5. Patients must relapse or be refractory after three or more lines of therapy, which at least include: one Proteasome Inhibitor (PI), one Immunomodulatory Drug (IMiD), and one anti-CD38 monoclonal antibody;
6. diagnosed as relapsed/refractory disease or primary refractory disease;
7. The last treatment is ineffective, or the disease progresses within 60 days after the end of the last therapy;
8. The patient has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade < 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy);
9. ECOG score 1-2 points and the expected survival period ≥ 3 months;

10. Liver, kidney and cardiopulmonary functions meet the following requirements:

    1. Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate aminotransferase (AST) ≤ 3 × ULN;
    2. Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min;
    3. Hemoglobin (Hb) ≥ 50 g/L without prior blood transfusion within 7 days;
    4. Baseline peripheral oxygen saturation > 92%;
    5. Corrected serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free (ionized, ionic) calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L);
    6. Left ventricular ejection fraction (LVEF) > 45%, without confirmed pericardiac effusion and abnormal electrocardiography with clinical significance;
    7. Without clinically significant pleural effusion;
11. Venous access could be established; without contraindications of apheresis.

Exclusion Criteria:

1. Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma;
2. Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter;
3. It is suspected that MM has involved the central nervous system or meninges and has been confirmed by MRI or CT, or there are other active central nervous system diseases;
4. Patients with Fahrenheit macroglobulinemia, POEMS syndrome, or primary AL, amyloidosis;
5. Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive; HIV antibody positive; CMV DNA titer is higher than the lower limit of detection of the research institution; EBV DNA titer is higher than the lower limit of detection of the research institution;
6. Patients have a severe allergic history;
7. Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure [New York Heart Association (NYHA) classification ≥ grade III];
8. Systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
9. Patients with acute/chronic graft-versus-host disease (GVHD) or requiring immunosuppressive therapy for GVHD within 6 months prior to screening;
10. Active autoimmune or inflammatory diseases of the nervous system;
11. Patients develop oncology emergencies and need to be treated before screening or infusion;
12. Uncontrolled infections that need antibiotics treatment;
13. Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis;
14. Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before apheresis;
15. Patients receive a major surgical operation within 4 weeks before lymphodepletion or do not recover completely before the enrollment; or plan to receive a major surgical operation during the study period;
16. Live attenuated vaccine within 4 weeks before screening;
17. Persons with serious mental illness;
18. Alcoholics or persons with a history of drug abuse;
19. Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion;
20. Any unsuitable to participate in this trial judged by the investigator.

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: Anti-BCMA CAR-T; BCMA-GPRC5D CAR-T is a novel CAR cell therapy for the treatment of relapsed/refractory multiple myeloma.	Biological: Anti-BCMA-GPRC5D CAR-T cells infusion; Subiects who meet the enrollment conditions will receive intravenous infusion of anti-BCMA-GPRC5D CAR-T Cells after lymphodepleting therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events(AE) after infusion	The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome are graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria.	within 2 years after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Overall Response Rate (ORR) is defined as the proportion of subjects achieving strict complete remission(sCR), complete response(CR), very good partial response(VGPR） and partial response(PR).	within 2 years after infusion
Concentration of CAR-T cells	Concentration of CAR-T cells measured by Flow cytometry after CAR-T infusion	Days 1,4, 7, 10, 14 ,21,28and months 2, 3, 6, 9, 12,18,24 after infusion
Progression-free survival(PFS)	Progression-free survival(PFS) refers to the time from cell reinfusion to the first assessment of tumor progression or death from any cause.	within 2 years after infusion
Overall survival(OS)	Overall survival (OS) refers to the time from the time the patient received an infusion of CAR-T cells until death (from any cause).	within 2 years after infusion

Collaborators and Investigators

• Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
• Collaborators: Guangzhou Bio-gene Technology Co., Ltd
• Investigators: Principal Investigator: Sanbin Wang, 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 17, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: BCMA-GPRC5D CAR-T
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: BG-CT-23-015

Drug and device information, study documents

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