NCT04184414Unknown早期 1 期
CD19-CART Cells in the Treatment of CD19+ r/r B Cell-derived Hematological Malignancies
PersonGen BioTherapeutics (Suzhou) Co., Ltd.1 个研究点 分布在 1 个国家目标入组 10 人开始时间: 2018年1月9日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- CR
研究概览
简要总结
CD19 is expressed in most B malignant tumors, especially in the former B cells ALL. This makes CD19 a natural target of immunotherapy. In terms of safety, the lack of B cells caused by CD19 targeted therapy will not cause life-threatening side effects (of course, Ig supplementation is necessary in the long-term B cell inhibition therapy). Moreover, the number of B cells can be restored after removing anti-CD19 treatment measures (such as anti-CD19 CART cells). In addition, CD19 has been chosen as the target of B-ALL therapy for the following reasons: ① as the BCR signal "amplifier", CD19 plays a role in PAX-5-mediated tumor formation; ② by activating MYC (as the oncogene controlled by PAX-5, C-MYC plays a key role in promoting the malignant proliferation of B cells), CD19 can cause B-ALL formation. Based on the above reasons, CD19 has become an ideal target in the treatment of B-cell cancer.
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
- •At the time of initial diagnosis, the age is 18-70 years old, regardless of gender or race
- •Morphological analysis showed that the load of lymphoma was ≥ 5%
- •Estimated survival time > 12 weeks
- •The main investigator and the attending physician of the patient think that there is no other feasible and effective alternative treatment, such as hematopoietic stem cell transplantation
- •Relapsed / refractory B-cell acute lymphocytic leukemia (all): A. objective remission rate (or) of grade 2 or higher bone marrow recurrence B. bone marrow relapse after allogeneic stem cell transplantation (SCT), SCT treatment is more than 6 months and in or state before cart-19 reinfusion C. refractory patients (CR status is not reached after 2 rounds of standard chemotherapy (CR refers to the load of myeloma detected by morphology < 5%)) D. Philadelphia chromosome positive (Ph +) and tyrosine kinase inhibitor (TKI) treatment failed twice or TKI failed to maintain or E. treatment with allogeneic SCT
- •For patients with relapse, CD19 was detected in bone marrow or peripheral blood by flow cytometry within 3 months before admission
- •CD19 expression on lymphoma cells: immunohistochemistry > 15% or flow cytometry > 30%
- •The main organ functions are sound, including: A. renal function: radioisotope glomerular filtration rate > 60 ml / min / 1.73 m2, or serum creatinine clearance rate in line with relevant age / gender standards B. alanine transferase (ALT) < 5 times the normal maximum value of the same age C. bilirubin < 2.0 mg / dl D. to achieve the minimum pulmonary function: ≤ grade I dyspnea and indoor blood oxygen concentration > 91% E. echocardiography or multi gated angiography (MUGA) showed that the left ventricular short axis shortening rate (LVSF) was ≥ 28%, or left ventricular ejection fraction (LVEF) was ≥ 45%
- •Karnofsky score (age ≥ 16 years old) ≥ 50 or zubrod-ecog-who score ≤ 2
- •Sign written informed consent and obtain consent before any research is carried out
- •When the above other conditions are met, the cell culture factory must receive fresh blood samples from patients. In the case of monocultured cells, they can only be accepted by the cell culture factory if the relevant tests are qualified
排除标准
- •Recurrence of isolated extramedullary diseases
- •The patient is accompanied by the following genetic syndrome: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any known myelofailure syndrome. Patients with Down syndrome are not included in the exclusion criteria
- •Patients with Burkitt's lymphoma / leukemia (i.e. patients with mature B cell all, B cell surface immunoglobulin positive (SIG +) and light chain kappa or lambda type, morphology Fab L3 or myc ectopic expression)
- •Patients with previous history of malignant tumor but cured skin or cervical carcinoma in situ and patients with inactive tumor are not included in the exclusion criteria
- •Previous use of gene therapy
- •Previous use of anti-CD19 / CD3 combination therapy or any other anti-CD19 treatment
- •Hepatitis B or C or HBV / HCV or other uncontrolled infection at the time of screening
- •Screening with HIV infection
- •Acute or chronic graft-versus-host reaction (GVHD) of level 2-4
- •Use the following drugs: A. steroid: it is forbidden to use within 72 hours before cart-19 reinfusion, but physiological steroid treatment dose (< 6 - 12 mg / m2 / day) or equivalent hydrocortisone can be used B. allogeneic cell therapy: no donor lymphocyte infusion (DLI) is allowed within 6 weeks before cart-19 reinfusion C. GVHD treatment: any GVHD treatment (such as calmodulinase inhibitor, methotrexate, mycophenolate ester, steroid (see above), rapamycin, thalidomide or immunosuppressive antibody (such as anti-CD20 / TNF / IL6 / IL6R)) must be stopped within 4 weeks before cart-19 infusion D. chemotherapy: I. The following drugs should be stopped for at least one week before cart-19 infusion, and it is better not to accompany or follow the lymphocyte elimination chemotherapy plan: hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25 mg / m2, cytarabine < 10 mg / m2 / day, asparaginase; II. The following drugs should be stopped for at least four weeks before cart-19 infusion: remedial chemotherapy (such as chlorine method) Lapin, cytarabine > 100 mg / m2, anthracycline drugs, cyclophosphamide), lymphocyte clearance chemotherapy drugs are not included in the exclusion criteria E. central nervous system (CNS) disease prevention: CNS prevention and treatment should be stopped at least one week before cart-19 reinfusion (such as MTX injection into spinal cord)
- •For CNS infiltration of malignant tumors, refer to the guidelines of national comprehensive cancer network (NCCN) cns-
- •Note: the patients with CNS diseases who have been effectively treated are not included in the exclusion criteria. The patients cannot participate in the drug trial within 30 days before screening
- •Pregnant or lactating women: 48 hours before reinfusion, the female test participants must carry out serum or urine pregnancy test, and the test result is positive
- •Women of childbearing age and all men did not take effective contraceptive methods within one year after cart-19 transfusion
研究组 & 干预措施
CART cells
Experimental
dosage：Once dose，1.0*10^6cells/kg CART cells Administration mode:Intravenous infusion
干预措施: CD19-CART (Drug)
结局指标
主要结局
CR
时间窗: 12 weeks after infusion of the study drug
Complete response rate (CR)
次要结局
- PR(12 weeks after infusion of the study drug)
- 2-year disease-free survival rate 2-year disease-free survival rate(12 weeks after infusion of the study drug)
研究者
研究点 (1)
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