Safety and Efficacy of Anti-CD20/CD30 CAR-T Cells in Subjects With Relapsed/Refractory Lymphoma
- Conditions
- Relapsed/Refractory Lymphoma
- Interventions
- Registration Number
- NCT06532643
- Lead Sponsor
- Shanghai First Song Biotechnology Co., LTD
- Brief Summary
This study is an exploratory clinical trial of a single-center, open-label, single-dose treatment of anti-CD20/CD30-CAR-T cells in subjects with relapsed/refractory lymphoma.
- Detailed Description
The study will enroll subjects with CD20 and CD30-positive lymphoma, CD20-positive lymphoma, or CD30-positive Hodgkin lymphoma. Subjects will receive a single infusion of anti-CD20/CD30-CAR-T cells after screening, PBMC collection, and lymphodepleting chemotherapy. Toxicity will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) from the National Cancer Institute. Safety of anti-CD20/CD30-CAR-T cell therapy will be evaluated through laboratory tests, including 12-lead electrocardiograms, vital sign checks, etc. Additionally, blood samples will be collected from subjects to study cellular pharmacokinetics and explore the effects of cell therapy on ferritin, C-reactive protein, and related cytokines.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 9
Not provided
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Subjects are not eligible to participate in this study if they meet any of the following criteria:
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MRI of the brain shows evidence of central nervous system lymphoma; active primary central nervous system DLBL, unless central nervous system involvement has been effectively treated (i.e., participant is asymptomatic), and there has been more than a 4-week gap since local treatment.
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Active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases with central nervous system involvement.
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History of or concurrent diagnosis of malignancies other than CD19+ malignancies.
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Clinically significant heart disease or arrhythmias that cannot be controlled with medication.
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Presence or suspicion of fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotics for treatment; uncomplicated urinary tract infections and uncomplicated bacterial pharyngitis are allowed.
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Positive for hepatitis B (HBsAg positive and HBV DNA >1000 copies/mL) and hepatitis C (positive for HCV antibodies); syphilis or human immunodeficiency virus (HIV) infection.
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Presence of any indwelling catheter or drainage tube (such as percutaneous nephrostomy, indwelling Foley catheter, bile drainage tube, or pleural/peritoneal/pericardial catheter); use of specialized central venous access devices like Port-A-Cath® or Hickman® catheters is allowed.
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History of using any of the following medications:
- Lenalidomide within 1 day before the apheresis.
- Idelalisib (oral PI3Kδ inhibitor) within 2 days before the apheresis.
- Short-acting targeted therapy (like tyrosine kinase inhibitors) within 72 hours before the apheresis.
- Venetoclax (BCL-2 inhibitor) within 4 days before the apheresis.
- Long-acting growth factors (like pegylated filgrastim) within 14 days before the apheresis, or short-acting growth factors or mobilization agents (like G-CSF/filgrastim, plerixafor) within 5 days before the apheresis.
- Pharmacological doses of corticosteroids (>5mg/day of prednisone or equivalent doses of other corticosteroids) or other immunosuppressive agents within 7 days before enrollment.
- Radiation therapy within 14 days before enrollment.
- Systemic cytotoxic drugs, including low-dose maintenance chemotherapy (cyclophosphamide, ifosfamide, bendamustine, methotrexate, or mercaptopurine, vincristine, etc.), within 14 days before enrollment. If bridging therapy is given after apheresis, there should be more than a 7-day gap between bridging therapy and CAR-T cell infusion.
- Anti-PD1 or anti-PDL1 within 4 weeks prior to enrollment.
- Live vaccines within 4 weeks prior to enrollment.
- Donor lymphocyte infusion (DLI) within 4 weeks prior to enrollment.
- Immune stimulation or immunosuppressive therapy (like interferon-α, interferon-β, IL-2, etanercept, infliximab, tacrolimus, cyclosporine, or mycophenolate mofetil) within 4 weeks prior to enrollment.
- Use of clofarabine or cladribine within 3 months prior to enrollment, or use of PEG-asparaginase within 3 weeks prior to enrollment.
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Active graft-versus-host disease (GVHD) rated ≥2 on the CIBMTR acute GVHD grading system or requires systemic steroids at doses greater than physiological levels.
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A history of autoimmune diseases in the past 2 years (like Crohn's disease, rheumatoid arthritis, or systemic lupus erythematosus) that has caused damage to end organs or requires systemic immunosuppression/systemic disease-modifying agents.
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A history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant heart diseases within the 12 months prior to enrollment.
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A history of genetic syndromes associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, or Schwachman-Diamond syndrome.
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A history of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation in the 6 months before enrollment. Subjects need to be on preventive anticoagulant medication.
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A history of other malignancies (except for non-melanoma skin cancer, in situ breast/cervical cancer, and other malignant tumors that have been effectively controlled without treatment in the past five years).
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Use of other investigational medicinal products within 30 days prior to screening.
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Pregnant or breastfeeding women of childbearing age. Women who have undergone surgical sterilization or are postmenopausal for at least 2 years are not considered of childbearing potential.
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Male and female subjects unwilling to practice contraception from the time they agree to treatment until 12 months after completing the lymphodepleting chemotherapy or CAR-T infusion (whichever is longer).
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Any medical activities that could interfere with the safety or efficacy evaluation of the study treatment.
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In the judgment of the investigator, subjects are unlikely to complete all required study visits or procedures (including follow-ups) or to comply with the study participation requirements.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Anti-CD20/CD30-CAR-T Cell Therapy anti-CD20/CD30-CAR-T cells Investigational product: anti-CD20/CD30-CAR-T cells Route of administration: Intravenous injection Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to the infusion of anti-CD20/CD30-CAR-T cells. Anti-CD20/CD30-CAR-T Cell Therapy Cyclophosphamide Investigational product: anti-CD20/CD30-CAR-T cells Route of administration: Intravenous injection Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to the infusion of anti-CD20/CD30-CAR-T cells. Anti-CD20/CD30-CAR-T Cell Therapy Fludarabine Investigational product: anti-CD20/CD30-CAR-T cells Route of administration: Intravenous injection Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to the infusion of anti-CD20/CD30-CAR-T cells.
- Primary Outcome Measures
Name Time Method Safety and tolerance 28 days after infusion of anti-CD20/CD30-CAR-T cells Incidence of dose-limiting toxicity (DLT)
Manufacturing feasibility 1 year Percentage of subjects for whom the required dose of anti-CD20/CD30-CAR-T cells can be successfully manufactured.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China