RecruitingPhase 1Phase 2NCT07032129

Sequential CAR-T Cells Targeting BCMA/GPRC5D in Patients With Relapsed/ Refractory Multiple Myeloma


Sponsor

Essen Biotech

Enrollment

60 participants

Start Date

Apr 29, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This is an open, single-arm, clinical study to evaluate the efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) targeting BCMA or GPRC5D or both sequentially in the treatment of Relapsed/ Refractory Multiple myeloma


Eligibility

Min Age: 21 YearsMax Age: 90 Years

Inclusion Criteria9

  • Expected survival time ≥3 months;
  • Subjects with recurrent/refractory Multiple Myeloma who have failed standard treatment or lack effective treatment, Including but not limited to systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, IGG4-associated diseases, primary Sjogren's syndrome, rheumatoid arthritis, connective tissue disease-associated interstitial lung disease, immune thrombocytopenia, primary biliary cholangitis, etc.
  • Histological evidence of non-suppurative destructive cholangitis and small bile duct destruction.
  • Liver and kidney function, cardiopulmonary function meet the following requirements:
  • Creatinine ≤1.5×ULN; (2) Electrocardiogram showed no clinically significant abnormal bands;
  • Blood oxygen saturation \>91% in non-oxygen state;
  • Total bilirubin ≤2×ULN; ALT and AST≤2.5 x ULN; ALT and AST abnormalities due to disease, such as liver infiltration or bile duct obstruction, were determined to be less than 5×ULN. If Gilbert syndrome is diagnosed, the total bilirubin index can be relaxed to ≤3.0×ULN and the direct bilirubin ≤1.5×ULN.
  • No serious mental disorders;
  • Can understand this test and has signed the informed consent.

Exclusion Criteria11

  • Malignant tumors other than R/R AID disease in the 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
  • Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference value range; Hepatitis C virus (HCV) Antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) Antibody positive; Syphilis positive;
  • Serious heart disease, including but not limited to unstable angina, myocardial infarction or bypass or stent surgery (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmia;
  • Systemic diseases that are deemed unstable by researchers: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment;
  • Active or uncontrollable infections (except mild genitourinary and upper respiratory tract infections) that require systemic treatment within 7 days prior to administration;
  • Pregnant or lactating women, and female subjects who plan pregnancy within 2 years after cell transfusion or male subjects whose partners plan pregnancy within 2 years after cell transfusion;
  • Patients who received CAR-T therapy or other gene-modified cell therapy before screening;
  • Participated in other clinical studies 1 month before screening;
  • Evidence of central nervous system invasion during subject screening;
  • Mental patients with depression or suicidal thoughts;
  • Situations considered unsuitable for inclusion by other researchers.

Interventions

BIOLOGICALBCMA/GPRC5D CAR-T cells

The intervention in this clinical trial involves a novel approach using BCMA/GPRC5D Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Patients in the trial will undergo the following regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. BCMA/GPRC5D Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, BCMA/GPRC5D CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial BCMA/GPRC5D CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.


Locations(1)

District One Hospital

Beijing, Beijing Municipality, China

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NCT07032129


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