Safety and Efficacy of GPRC5D CAR-T Cell Therapy in Relapsed/Refractory Plasma Cell Disorders

Official title

Clinical Study on Safety and Efficacy of GPRC5D CAR-T Cell Therapy in Relapsed/Refractory Plasma Cell Disorders

Overview

This study is an open-label, single-arm, dose-escalation and expansion, prospective clinical trial. It enrolls patients with relapsed/refractory plasma cell disorders, administers GPRC5D CAR-T cell therapy, follows up to observe adverse reactions after medication, collects relevant data on treatment efficacy, evaluates the safety and efficacy of CAR-T cells, and simultaneously investigates the cellular kinetic characteristics of CAR-T cells.

Interventions

• Biological GPRC5D CAR-T cell intravenous infusion
  GPRC5D CAR-T cell intravenous infusion

Primary outcome measures

• Monitor and record adverse events [Time frame: up to two years after the CAR-T cell infusion]
• Overall Response Rate [Time frame: up to two year after the CAR-T cell infusion]

Secondary outcome measures (1)

• Cell pharmacokinetics Dynamic indicators [Time frame: up to one month after the CAR-T infusion]

Eligibility criteria

Inclusion criteria

Subjects must meet all of the following criteria：

• According to the World Health Organization (WHO) Classification of Haematopoietic and Lymphoid Tissue Tumours (2022), patients with relapsed/refractory plasma cell disorders that have received adequate treatment and lack effective therapeutic options, including: multiple myeloma, plasma cell leukemia, extramedullary plasmacytoma, solitary plasmacytoma, or primary amyloidosis.i) Relapsed: Disease progression occurs after one or more prior treatments, requiring salvage therapy, and does not meet the criteria for refractory disease.ii) Refractory: No response to initial treatment regimen or salvage therapy, or disease progression within 60 days after treatment. No response is defined as failure to achieve minimal response (MR) or disease progression during treatment.
• The subject's predicted survival time is not less than three months.
• Tumor cells confirmed to be GPRC5D positive by Flow Cytometry (FCM) or Immunohistochemistry.
• The subject failed autologous and allogeneic hematopoietic stem cell transplantation.
• Age 14-75 years (inclusive), both genders eligible.
• ECOG performance status ≤ 2.
• HGB≥70g/L(transfusion permitted).
• The functions of vital organs need to meet the following conditions: ①Creatinine ≤ 2.5 × ULN or Cockcroft-Gault creatinine clearance > 50 ml/min (excluding decreased serum creatinine clearance due to lymphoma mass compression), Combination with hemodialysis treatment is permitted. ②LVEF≥50%,② Oxygen saturation ≥90%,③ SCr≤2.5ULN,④ALT and AST≤3ULN,TBil≤2ULN. In the investigator's judgment, if organ dysfunction is associated with the current disease, the enrollment decision will be made by the investigator.
• Subjects intending to conceive must agree to use contraception prior to study enrollment and for six months post-study. In the event of pregnancy or suspected pregnancy, they should promptly notify the investigator.
• The subject or guardian understands and signs the Informed Consent Form (ICF).

Exclusion criteria

Any of the following conditions will not be eligible for enrolment:

• Severe heart failure with left ventricular ejection fraction (LVEF) < 50%.
• History of severe pulmonary function impairment.
• Concurrent other progressive malignant tumors.
• Concurrent severe infection that cannot be effectively controlled.
• Concurrent severe autoimmune disease or congenital immunodeficiency.
• Active hepatitis (hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) positive with HBV DNA copy number greater than the upper limit of normal at the study center; Anti-HCV positive with HCV-RNA copy number greater than the upper limit of normal at the study center).
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection.
• History of severe allergy to biological products (including antibiotics).
• Received inactivated vaccines such as influenza vaccine, COVID-19 vaccine within 4 weeks prior to screening, or received live attenuated vaccines (such as measles, varicella vaccines) within 8 weeks.
• Allogeneic hematopoietic stem cell transplant patients with persistent acute graft-versus-host disease (GVHD) one month after discontinuation of immunosuppressive agents.
• Patients with other severe physical or mental illnesses or laboratory abnormalities that may increase the risk of study participation or interfere with study results, and patients considered unsuitable for this study 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

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07365059 · XBAP2025-9

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗