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

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Incidence of adverse events(AE) after infusion [Time frame: within 2 years after infusion]

Secondary outcome measures (4)

• Overall Response Rate (ORR) [Time frame: within 2 years after infusion]
• Concentration of CAR-T cells [Time frame: Days 1,4, 7, 10, 14 ,21,28and months 2, 3, 6, 9, 12,18,24 after infusion]
• Progression-free survival(PFS) [Time frame: within 2 years after infusion]
• Overall survival(OS) [Time frame: within 2 years after infusion]

Eligibility criteria

Inclusion criteria

• 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;
• Age 18-75 years old, gender unlimited;
• Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG);
• 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;
• 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;
• diagnosed as relapsed/refractory disease or primary refractory disease;
• The last treatment is ineffective, or the disease progresses within 60 days after the end of the last therapy;
• 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);
• ECOG score 1-2 points and the expected survival period ≥ 3 months;
• Liver, kidney and cardiopulmonary functions meet the following requirements:

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

Exclusion criteria

• Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma;
• 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;
• 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;
• Patients with Fahrenheit macroglobulinemia, POEMS syndrome, or primary AL, amyloidosis;
• 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;
• Patients have a severe allergic history;
• 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 \[New York Heart Association (NYHA) classification ≥ grade III\];
• Systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
• Patients with acute/chronic graft-versus-host disease (GVHD) or requiring immunosuppressive therapy for GVHD within 6 months prior to screening;
• Active autoimmune or inflammatory diseases of the nervous system;
• Patients develop oncology emergencies and need to be treated before screening or infusion;
• Uncontrolled infections that need antibiotics treatment;
• Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis;
• Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before apheresis;
• 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;
• Live attenuated vaccine within 4 weeks before screening;
• Persons with serious mental illness;
• Alcoholics or persons with a history of drug abuse;
• Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion;
• Any unsuitable to participate in this trial judged by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sanbin Wang — Kunming

Identifiers

NCT: NCT06515262 · BG-CT-23-015

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗