Multicentre Phase I/IIa Study of Infusion of Autologous Peripheral Blood T Lymphocytes Expanded and Genetically Modified Using Sleeping Beauty Family Transposons to Express a Chimeric Antigenic Receptor With Anti-CD19 Specificity Conjugated to the 4-1BB Co-stimulatory Region and CD3z and huEGFRt Signal Transmission (TranspoCART19) in Patients With Relapsed or Refractory B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 27
- 试验地点
- 8
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
The goal of this clinical trial is to to evaluate the safety and efficacy of TranspoCART19 in patients with relapsed/refractory B-lymphoma. The main questions it aims to answer are:
Maximum tolerated dose (MTD) Response rates Participants will be treated with the investigational medicinal product and will be followed for 36 months.
详细描述
This clinical trial is a Phase I/II, pilot, open-label, national, prospective, multicentre, non-randomised, open-label study to evaluate the safety and efficacy of TranspoCART19 in patients with relapsed/refractory B-lymphoma whose prognosis is less than 2 years.
Phase I: Dose escalation phase with a classic 3+3 design, in which three dose levels of TranspoCART19 will be evaluated: 1 x 106 cells/kg, 3 x106 cells/kg and 5 x 106 cells/kg. The maximum number of patients included in this phase will be 18.
Phase II: an expansion cohort with the maximum tolerated dose (MTD) determined in Phase I.
Patients will be included in the expansion cohort up to a total of 27, including Phase I patients.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with relapsed or refractory B-cell lymphoma (Diffuse large B-cell lymphoma, Primary diffuse large B-cell lymphoma of the Central Nervous System (CNS), Mantle cell lymphoma, Follicular lymphoma grades 1, 2 or 3a or Marginal lymphoma, including splenic, nodal and MALT).
- •Age over 18 years and under 80 years.
- •Functional status Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Patients with ECOG 2 may be included if motivated by haematological disease (Annex 3).
- •Adequate bone marrow haematopoietic reserve.
- •Life expectancy of at least 2 months.
- •Adequate venous access for lymphapheresis. Absence of contraindications for lymphapheresis.
- •Signed informed consent (patient or legal guardian).
排除标准
- •Patients who, in the opinion of a physician, may benefit from other approved potentially curative therapeutic options, including commercial CAR-Ts.
- •Treatment with any experimental or non-commercialised substance in the four weeks prior to recruitment, or who are actively participating in another therapeutic clinical trial.
- •Diagnosis of another neoplasm, past or present. Patients who have been in complete remission for more than 3 years, or with a history of non-melanoma skin cancer or completely resected carcinoma in situ may be included. A current or previous history of clonal T-lymphocytes is also an exclusion criterion.
- •Early relapse after allogeneic haematopoietic stem cell transplantation (less than 3 months for lymphapheresis, less than 6 months for TranspoCART19 infusion) or patients on active immunosuppressive treatment for graft-versus-recipient disease (corticosteroids or other systemic immunosuppressants).
- •Active infection requiring systemic medical treatment.
- •HIV infection.
- •Concurrent and uncontrolled medical illnesses including cardiac, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological or psychiatric illnesses that in the opinion of the investigator pose a risk to the patient.
- •Positive serology for hepatitis B, defined as a positive test for HBsAg. In addition, if the patient is HBsAg negative but has anti-HBcore antibodies, a hepatitis B virus DNA test will be required, and if the result is positive the patient will be excluded.
- •Positive serology for hepatitis C virus (HCV), defined as a positive test for anti-HCV antibodies that is confirmed by Recombinant immunoblot assay (RIBA).
- •Severe organ involvement, defined as cardiac ejection fraction <40%; diffusing capacity of the lungs for carbon monoxide (DLCO) <40%; calculated glomerular filtration rate <30 ml/min; baseline O2 saturation <92%; bilirubin > 2 times upper limit of normal (unless due to Gilbert's syndrome) or transaminases > 2.5 upper limit of normal.
- •Pregnant or lactating women. Women of childbearing age should have a negative pregnancy test at screening.
- •Women of childbearing age, including those whose last menstrual cycle was in the year prior to screening, who are unable or unwilling to use highly effective methods of contraception* from the start of the study until the end of the study.
- •Men who are unable or unwilling to use highly effective methods of contraception* from the start of the study until the end of the study.
- •Need to take glucocorticoids chronically in doses greater than 10 mg/day of prednisone (or equivalent) or other chronic immunosuppressants.
- •Previous anti-CD19 CAR-T therapy. Previous treatment with other anti-CD19 strategies is permitted, provided that CD19 expression has been confirmed in the tumour biopsy.
- •Hypersensitivity to the active substance or to any of the excipients.
研究组 & 干预措施
TranspoCART19 cells
Adult differentiated, autologous, peripheral blood T lymphocytes, expanded and genetically modified.
干预措施: CAR-T cells therapy (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: 1 month
Determine the maximum tolerated dose (MTD) and/or recommended dose of TranspoCART19 cells in patients with relapsed or refractory B-cell lymphoma.
Efficiency
时间窗: 3 month
Determine best response rate achieved (overall and complete).
次要结局
- Procedure-related mortality (PRM)(1 month - 3 month)
- Toxicity assessment(1 month - 3 month - 12 month - 36 month)
- Response (overall and complete)(1 month - 3 month - 12 month - 36 month)
- Duration of response(36 month)
- Progression-free survival (PFS)(12 month - 24 month)
- Overall survival (OS)(12 month - 24 month)
- Perceived general well-being(3 month -6 month -12 month)
研究者
Esperanza Lopez Franco
Scientific
Fundacion Instituto De Estudios De Ciencias De La Salud De Castilla Y Leon