Investigating the Safety and Efficacy of Anti-CD7 CAR-T Cell Immunotherapy in Patients With Relapse and Refractory T-cell Acute Lymphoblastic Leukemia or T Lymphoblastic Lymphoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Number of patients with dose-limiting toxicity
研究概览
简要总结
T cells are a type of immune cell. Like other cells of the body, T Cells can develop cancer. T cell cancers mainly include T cell leukaemia and T cell lymphoma, both of which have a relatively poor prognosis. Currently, patients with relapsed/refractory type (the name given to cancer that reappears or grows again after a period of no changes or signs of cancer) of this leukaemia or lymphoma have limited choices for treatment. CAR-T cells are immune cells that are engineered to target specific cell markers. For example, CAR-T cells targeting the marker CD19 have shown great effectiveness in the treatment of B cell tumors that carry this marker. Here investigators construct a new universal CAR-T design targeting CD7 which is found on the cells of relapsed/refractory type T cell leukaemia and lymphoma and hope to test its safety and efficiency in the treatment of relapsed/refractory type T cell leukaemia and lymphoma.
详细描述
Who can participate? Patients diagnosed with relapsed/refractory T cell leukaemia or lymphoma. Both genders, aged 2-25 years old.
What does the study involve? Enrolled participants are randomly chosen to receive one of three different dose levels of CAR-T cells.
- Dose level one: 0.6×10^7 cells/kg;
- Dose level two: 1×10^7 cells/kg;
- Dose level three: 1.5×10^7 cells/kg. Before CAR-T infusion, all participants will receive a preconditioning therapy including several chemotherapy agents or other interventions that are required to help the effect of the CAR-T cells. After completion of preconditioning therapy, infusion of the CAR-T cells via a tube into the vein needs to start within 1 week. Participants will receive one infusion of CAR-T cells which will take between 15 and 30 mins. All participants will have a blood test before infusion and at 4, 7, 10 and 14 days following infusion to measure their response to the treatment and some further tests will be required in some participants.
What are the possible benefits and risks of participating? The universal CAR-T cells targeting CD7 may lead to durable disease control and long term survival. The main risks of participating include cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS).
Where is the study run from? Haematology department of 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China (China).
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
- 2 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •2 to 25 years
- •Diagnosed with relapsed and refractory CD7 + T cell acute lymphocytic leukemia (T-ALL) or relapsed and refractory CD7 + T lymphoblastic lymphoma (T-LBL)
- •Quantifiable tumor burden
- •Eastern cooperative oncology group (ECOG) performance status of 0 to 1
- •Life expectancy ≥12 weeks
- •Adequate organ function defined as:
- •Serum ALT/AST ≤2.5 ULN
- •Creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min
- •PT and APTT≤1.5 ULN
- •Total bilirubin ≤1.5 ULN
- •Cardiac ejection fraction ≥45%
- •No clinically significant ECG findings
- •Baseline oxygen saturation >90% on room air
- •Recovered from acute toxic effects of prior chemotherapy ≥one week before entering this study
- •Agreement to use of medical-approved-contraception during the period of trial and in 1 year after cell transfusion therapy
- •Signed informed consent form
排除标准
- •Diagnosis of other malignancy (except non-melanoma and cervical carcinoma in situ, bladder cancer, breast cancer that have a disease-free survival of more than 5 years)
- •Severe mental disorders
- •History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome
- •Grade 2-4 acute graft-versus-host disease (GVHD) (Glucksberg criteria) or extensive chronic GVHD (Seattle criteria)
- •Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement, unstable angina pectoris, or other clinically prominent heart disease within one year before enrollment
- •History or presence of CNS disorder, including but not limited to: seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
- •Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA
- •Presence of fungal, bacterial, viral, or other infection that is uncontrolled
- •Severe allergies
- •History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
- •History or diagnosis of pulmonary fibrosis
- •Participation in other clinical trials ≤4 weeks prior to enrollment
- •Concomitant disease that require systemic steroids or other immune suppressive therapy during the study period in researcher's judgement
- •Patients who are contraindicated to cyclophosphamide, fludarabine
- •Allogeneic cell therapy (such as donor lymphocyte infusion, DLI) ≤6 weeks prior to enrollment
- •Poor adherence due to physical, family, social, geographic, and other factors, who cannot follow the research plan and follow-up plan
- •Pregnant and lactating women
- •Any other conditions that researcher think it is inappropriate for the subject to anticipate the trial
研究组 & 干预措施
Target CD7 CAR-T cells
Three dose levels will be evaluated. The CAR-T cells will be administered with Cytoxan and fludarabine.
干预措施: Target CD7 CAR-T cells (Biological)
结局指标
主要结局
Number of patients with dose-limiting toxicity
时间窗: up to 4 weeks after target CD7 CAR-T cells infusion
Dose-limiting toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE v5.0) at 4 weeks following target CD7 CAR-T cells infusion
次要结局
- Overall survival (OS)(24 weeks after target CD7 CAR-T cells infusion)
- Overall response rate (ORR)(4 weeks, 12 weeks, 24 weeks after target CD7 CAR-T cells infusion)
- Progression-free survival (PFS)(24 weeks after target CD7 CAR-T cells infusion)
- Duration of remission (DOR)(24 weeks after target CD7 CAR-T cells infusion)