NCT06519344尚未招募早期 1 期
An Exploratory Clinical Study Evaluating the Safety and Efficacy of Intravenous Anti-CD20/CD30-CAR-T Cell Infusion in Relapsed/Refractory Lymphoma Patients.
Shanghai Tongji Hospital, Tongji University School of Medicine0 个研究点目标入组 12 人开始时间: 2024年7月31日最近更新:
适应症
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 12
- 主要终点
- Incidence of dose-limiting toxicity
研究概览
简要总结
This study is a single-center,open-label,single-dose clinical trial of anti-CD20/CD30-CAR-T cell therapy in relapsed/refractory B-cell tumor patients after lymphocyte depletion pre-treatment.
In this study phase,a traditional "3+3"trial design is employed for dose escalation.
详细描述
This study is a single-center, open-label, single-dose clinical trial of anti-CD20/CD30-CAR-T cell therapy in relapsed/refractory lymphoma patients after lymphocyte depletion pre-treatment.
The study aims to include patients with CD20/CD30 double-positive relapsed/refractory lymphomas, CD20-positive relapsed/refractory B-cell lymphomas (including patients who have relapsed after anti-CD19-CAR-T cell therapy), and CD30-positive Hodgkin lymphoma. Participants will undergo screening, peripheral blood mononuclear cell (PBMC) collection, and lymphocyte depletion pre-treatment before receiving a single infusion of anti-CD20/CD30-CAR-T cells.
Throughout the study, efficacy assessments will occur at baseline and at 4 weeks post-treatment, and subsequently at 3 months, 6 months, 9 months, and 12 months, until disease progression (PD), relapse, change of treatment regimen, death, intolerable toxicity, investigator decision, or voluntary withdrawal (whichever comes first).
Safety evaluations of anti-CD20/CD30-CAR-T cell therapy will be conducted according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) by laboratory tests, 12-lead electrocardiograms, vital signs, and physical examinations. Additionally, blood samples will be collected to assess cellular pharmacokinetics and explore the effects of cellular therapy on ferritin, C-reactive protein, and related cytokines.
The study is designed as an exploratory research project, subject to implementation conditions at the research center. Dose escalation during this study phase will follow a traditional "3+3" trial design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1) Voluntary participation in the clinical study; complete understanding by self or legally authorized guardian, informed of the study, and signing the Informed Consent Form (ICF); willing and able to comply with all trial procedures.
- •(2) Age between 18 and 70 years.
- •(3) Patients refractory or relapsed after current standard treatments (including allogeneic or autologous hematopoietic stem cell transplantation), and unsuitable for other treatment options such as second hematopoietic stem cell transplantation. Refractory/relapsed lymphoma is defined as:
- •No response to first-line therapy (primary refractory disease, excluding subjects intolerant to first-line therapy):
- •- Progression of Disease (PD) assessment after first-line treatment
- •Best response of Stable Disease (SD) after at least 4 cycles of first-line treatment (e.g., 4 cycles of RCHOP), with SD maintenance duration not exceeding 6 months after the last dose.
- •No response to second-line or subsequent therapies:
- •PD as best response to the most recent treatment regimen
- •Best response of SD after at least 2 cycles of last-line treatment, with SD maintenance duration not exceeding 6 months after the last dose.
- •Refractory post autologous stem cell transplantation (ASCT):
- •Disease progression or relapse ≤12 months after ASCT (relapsing subjects must have biopsy-proven relapse)
- •If salvage therapy is performed post-ASCT, subjects must have had no response or relapse after the last-line treatment.
- •Relapsed or refractory disease after two or more lines of systemic therapy.
- •(4) Lymphoma patients with target antigens meeting the following criteria:
- •CD20/CD30 double-positive lymphomas
- •Relapse after anti-CD19-CAR-T cell therapy, and CD20-positive lymphomas
- •Never received anti-CD19-CAR-T cell therapy, CD20-positive lymphomas
- •CD30-positive Hodgkin lymphoma.
- •(5) Included lymphoma subtypes:
- •DLBCL-NOS (Diffuse Large B-Cell Lymphoma, not otherwise specified)
- •Primary mediastinal large B-cell lymphoma (PMBCL)
- •Transformed follicular lymphoma (TFL), previously treated with follicular lymphoma chemotherapy, subsequently transformed into DLBCL, refractory disease
- •Mantle cell lymphoma
- •High-grade B-cell lymphoma
- •Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
- •Hodgkin lymphoma (HL).
- •(6) ECOG performance status ≤
- •(7) Expected survival of at least 12 weeks.
- •(8) Adequate venous access (for single collection), and no other contraindications for blood cell separation.
- •(9) Laboratory requirements at screening, with no hematologic evaluation within 7 days of receiving growth factors (long-acting granulocyte colony-stimulating factor (G-CSF/PEG-CSF) requires a 2-week interval):
- •Absolute neutrophil count ≥1.0×10^9/L;
- •Hemoglobin ≥60 g/L (without red blood cell transfusion within 7 days);
- •Platelets ≥50×10^9/L (CLL indication unrestricted);
- •Serum total bilirubin ≤1.5× upper limit of normal (ULN); or ≤3× ULN if liver tissue invasion by tumor;
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5× ULN, AST/ALT ≤5× ULN if liver tissue invasion by tumor;
- •Creatinine <1.5× ULN and estimated glomerular filtration rate ≥60 mL/minute.
- •(10) Left ventricular ejection fraction ≥45%, echocardiogram (ECHO) showing no clinically significant pericardial effusion (excluding minimal or physiological effusions), and no clinically significant findings on electrocardiogram.
- •(11) Baseline oxygen saturation >92% without supplemental oxygen.
- •(12) Women of childbearing potential must have a negative serum or urine pregnancy test result (women who have undergone surgical sterilization or who are at least 2 years postmenopausal are not considered of childbearing potential).
排除标准
- •Here is the translation of the exclusion criteria for participants in a clinical study:
- •Evidence of central nervous system lymphoma on brain MRI; active primary central nervous system DLBCL, unless CNS involvement has been effectively treated (i.e., participant is asymptomatic) and there has been a local treatment interval of >4 weeks prior to enrollment.
- •Active central nervous system diseases such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases with central nervous system involvement.
- •History of or concurrent malignancies other than CD19+ malignancies.
- •Clinically significant cardiac disease, or arrhythmias not controlled by medication.
- •Presence or suspicion of uncontrolled fungal, bacterial, viral, or other infections requiring intravenous antibiotics; simple urinary tract infections and uncomplicated bacterial pharyngitis are allowed.
- •Hepatitis B (positive hepatitis B surface antigen and hepatitis B DNA >1000 copies/mL) and hepatitis C (positive hepatitis C antibody).
- •Presence of any indwelling catheters or drainage tubes (e.g., percutaneous nephrostomy tube, Foley catheter, bile drainage tube, pleural/peritoneal/pericardial catheter); specialized central venous access devices like Port-A-Cath® or Hickman® catheters are allowed.
- •Use of the following medications prior to:
- •1) Ibrutinib within 1 day before apheresis. 2) Idelalisib (oral PI3Kδ inhibitor) within 2 days before apheresis. 3) Short-acting targeted therapy (such as tyrosine kinase inhibitors) within 72 hours before apheresis.
- •4) Venetoclax (BCL-2 inhibitor) within 4 days before apheresis. 5) Long-acting growth factors (such as pegfilgrastim) within 14 days before apheresis, or short-acting growth factors or mobilizing agents (such as granulocyte colony-stimulating factor (G-CSF)/filgrastim) within 5 days before apheresis.
- •6) Pharmacologic doses of corticosteroid therapy (>5 mg/day prednisone or equivalent) and other immunosuppressive drugs within 7 days before enrollment.
- •7) Radiotherapy within 14 days before enrollment. 8) Systemic cytotoxic drugs within 14 days before enrollment, including daily or weekly low-dose maintenance chemotherapy (e.g., cyclophosphamide, fludarabine, bendamustine, chlorambucil, methotrexate, vinblastine).
- •If bridging therapy is administered post-apheresis, there must be at least a 7-day interval between bridging therapy and CAR-T cell infusion.
- •9) Anti-PD1 or anti-PDL1 therapy within 4 weeks before enrollment. 10) Vaccination within 4 weeks before enrollment. 11) Donor lymphocyte infusion (DLI) within 4 weeks before enrollment. 12) Immunostimulatory or immunosuppressive therapy within 3 months before enrollment (such as interferon-α, interferon-β, IL-2, lenalidomide, efalizumab, alemtuzumab, cyclosporine, or methotrexate).
- •(9) Active graft-versus-host disease (GVHD) using the CIBMTR acute GVHD grading system ≥ grade 2 or requiring systemic steroids greater than physiological doses.
- •(10) History in the past 2 years of autoimmune diseases causing end-organ damage or requiring systemic immunosuppressive/disease-modifying agents, such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus.
- •(11) History in the past 12 months of myocardial infarction, cardiac vascular procedures or stent implantation, unstable angina, or other clinically significant cardiac diseases.
- •(12) History of genetic syndromes with bone marrow failure, such as Fanconi anemia, Costello syndrome, Shwachman-Diamond syndrome.
- •(13) Symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation therapy within 6 months before enrollment. Subjects requiring prophylactic anticoagulation are allowed.
- •(14) History of concurrent or prior malignancies (excluding basal cell carcinoma of the skin, in situ carcinoma of the breast/cervix, and other malignancies effectively controlled without treatment within the past five years).
- •(15) Use of other investigational medicinal products within 30 days before screening.
- •(16) Pregnant or lactating women of childbearing potential. Women who have undergone surgical sterilization or who are at least 2 years postmenopausal are not considered of childbearing potential.
- •(17) Participants unwilling to use contraception from agreeing to treatment until completion of lymphocyte depletion chemotherapy or CAR-T cell infusion within 12 months (whichever is longer).
- •(18) Any medical activities that could potentially interfere with the safety or efficacy evaluation of the study treatment.
- •(19) According to the investigator's judgment, participants who are unlikely to complete all study visits or procedures required by the protocol (including follow-ups), or comply with the requirements of participating in the study.
结局指标
主要结局
Incidence of dose-limiting toxicity
时间窗: Up to 28 days from CAR-T infusion
The proportion of patients receiving CAR-T cells who encounter dose-limiting toxicities(DLTs). Safety evlauations are performed in accordance with the NCI-CTCAE version 5.0 standards(Cytokine Release Syndrome and neurotoxicity will be graded based on ASTCT/ASBMT grading criteria).
次要结局
未报告次要终点
研究者
Aibin Liang，MD，Ph.D.
professor,Chief Physician,Vice President of Tongji Hospital, Tongji University School of Medicine etc.
Shanghai Tongji Hospital, Tongji University School of Medicine
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