肿瘤细胞治疗研究
英文原题：CD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)
CD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
这是一项 I 期注册临床试验，评估 CD19T 细胞治疗非霍奇金淋巴瘤、淋巴瘤、急性淋巴细胞白血病的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 13 例。试验地点：美国 · 休斯顿（共 2 个中心）。登记号：NCT03774654。
不限性别 · ≥ 3 Years 且 ≤ 75 Years
治疗阶段纳入标准： 1. 确诊CD19阳性B细胞淋巴瘤或白血病（ALL或CLL）； 2. 疾病符合相应队列要求： * A队列（非ALL）：非惰性淋巴瘤患者至少接受过2线治疗（惰性淋巴瘤须包括抗CD20抗体）后复发/难治；CLL患者至少接受过2线包括伊布替尼和维奈克拉的治疗后复发/难治；侵袭性或高度侵袭性淋巴瘤患者至少接受过2线包括抗CD20抗体和蒽环类药物的治疗后复发/难治，且不适合自体干细胞移植。不适合移植包括挽救治疗后疾病无应答和干细胞动员失败； * B队列（ALL）：ALL患者至少接受过2线治疗后复发/难治； 3. 按现行标准有可测量疾病（淋巴瘤按Lugano标准、CLL按IWG标准，ALL需有可检出疾病）； 4. 年龄≥3岁且≤75岁； 5. 胆红素<ULN的2倍（Gilbert综合征患者<3倍）； 6. AST和ALT<ULN的5倍； 7. 估算GFR≥50 mL/min； 8. 室内空气脉搏血氧饱和度≥90%； 9. Karnofsky或Lansky评分≥70； 10. 经入组医生评估，既往化疗的急性毒性已恢复；若部分化疗影响预计长期存在，只要满足其他条件仍可入组； 11. 预期寿命>12周； 12. 有性生活者同意研究期间及研究结束后6个月内采取高效避孕措施，男性伴侣须使用安全套； 13. 签署知情同意书，确认了解研究性质、潜在获益和毒性；患者或监护人将获得知情同意书副本。 治疗阶段排除标准： 1. 当前接受任何试验药物，或过去6周内接受过任何细胞治疗； 2. 对含鼠源蛋白制品有超敏反应史； 3. 既往发生过2–4级GVHD； 4. 妊娠或哺乳； 5. 活动性HIV或HTLV感染； 6. 活动性HBV或HCV感染； 7. 活动性且未控制的细菌、真菌或其他病毒感染。
Treatment Inclusion Criteria:
1. Diagnosis of CD19-positive B-cell lymphoma or leukemia (ALL or CLL).
2. The disease is:
Cohort A (non-ALL patients):
1. Relapsed or refractory after two or more lines of therapy, including a CD20 antibody, if an indolent lymphoma.
2. Relapsed or refractory after two or more lines of therapy, including ibrutinib and venetoclax, if CLL.
3. Relapsed or refractory after two or more lines of therapy, including a CD20 antibody and an anthracycline, and the patient is ineligible for autologous stem cell transplantation, if an aggressive or highly aggressive lymphoma.
* Ineligibility for autologous stem cell transplantation includes non-responsive disease after salvage therapy and failure to mobilize stem cells for transplant.
Cohort B (ALL patients)
a. Relapsed or refractory after two or more lines of therapy, if ALL.
3. Measurable disease by current criteria (Lugano criteria for lymphomas, IWG criteria for CLL, and detectable disease for ALL).
4. Age ≥ 3 and ≤75 years.
5. Bilirubin \< 2 times (3 times if Gilbert syndrome) upper limit of normal
6. AST and ALT less than 5 times the upper limit of normal.
7. Estimated GFR ≥ 50 mL/min.
8. Pulse oximetry of ≥ 90% on room air
9. Karnofsky or Lansky score of ≥ 70.
10. Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
11. Life expectancy of greater than 12 weeks.
12. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
13. Patients must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.
Treatment Exclusion Criteria:
1. Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks.
2. History of hypersensitivity reactions to murine protein-containing products.
3. History of grade 2 to 4 graft-versus-host disease (GVHD)
4. Pregnant or lactating.
5. Active infection with HIV or HTLV.
6. Active infection with HBV or HCV.
7. Uncontrolled active bacterial, fungal or other viral infection.以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Dose Limiting Toxicity (DLT) Rate · DLT rate is defined as the proportion of subjects with DLT evaluated as per the NCI CTCAE v5.0 with the exception of CRS and neurological toxicities that are related to T-cell infusions. GVHD will be graded according to the BMT CTN Technical Manual of Procedures v3.0. · 4 weeks post T cell infusion
次要终点：Overall Response Rate According to the Lugano Criteria for Non-Hodgkin Lymphomas (for NHL) and the IWG (for CLL), or the Proportion of Patients With Morphologic CR (for ALL).
适用于非ALL的复发/难治性B细胞NHL或白血病患者。评估三个剂量水平。患者接受环磷酰胺和氟达拉滨淋巴细胞清除化疗，随后输注CD19.CAR-aNKT细胞。
适用于复发/难治性B细胞ALL患者。评估三个剂量水平。患者接受环磷酰胺和氟达拉滨淋巴细胞清除化疗，随后输注CD19.CAR-aNKT细胞。
本研究面向治疗后复发或未缓解的淋巴瘤或白血病患者。由于目前没有针对该类癌症的标准治疗，研究邀请患者参加使用特殊免疫细胞的基因转移研究。人体有多种抵抗感染和疾病的方式，但单一机制可能不足以对抗癌症，因此本研究结合抗体与免疫细胞。抗体是可保护机体免受细菌等疾病侵袭的蛋白质；免疫细胞（淋巴细胞）是能够杀伤包括肿瘤细胞在内其他细胞的特殊血细胞。二者均已用于癌症治疗并显示出潜力，但尚不足以治愈大多数患者。 研究使用抗CD19抗体。CD19是淋巴瘤细胞表面的一种物质，抗CD19抗体已用于治疗淋巴瘤和白血病。本研究将抗CD19抗体连接到NKT细胞上。NKT是能够杀伤肿瘤细胞、但单独作用时杀伤能力有限的一类特殊淋巴细胞；抗体连接到细胞上后形成嵌合受体。研究者还发现，加入CD28等刺激淋巴细胞的蛋白可增强NKT功能并延长细胞在体内的存活，但可能仍不足以杀死淋巴瘤细胞；再加入IL-15这一刺激蛋白，可能进一步提高细胞杀伤能力。 研究者将把抗CD19嵌合受体、CD28和IL-15导入健康供者培养的NKT细胞，称为ANCHOR细胞，并输注给表面表达CD19的淋巴瘤或白血病患者。ANCHOR细胞为尚未获美国FDA批准的试验性产品。本研究旨在确定安全的最大剂量，了解细胞在体内的持续时间及副作用，并评估其是否可能帮助淋巴瘤或白血病患者。
This study is for patients who have lymphoma or leukemia that has come back or has not gone away after treatment. Because there is no standard treatment for this cancer, patients are being asked to volunteer for a gene transfer research study using special immune cells. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and immune cells. Antibodies are types of proteins that protect the body from bacteria and other diseases. Immune cells, also called lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and lymphocytes have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients. The antibody used in this study is called anti-CD19. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to the NKT cells, a special type of lymphocytes that can kill tumor cells but not very effectively on their own. When an antibody is joined to a T cell in this way it is called a chimeric receptor. Investigators have also found that NKT cells work better if proteins are added that stimulate lymphocytes, such as one called CD28. Adding the CD28 makes the cells last for a longer time in the body but maybe not long enough for them to be able to kill the lymphoma cells. It is believed that by adding an extra stimulating protein, called IL-15, the cells will have an even better chance of killing the lymphoma cells. In this study the investigators are going to see if this is true by putting the anti-CD19 chimeric receptor with CD28 and the IL-15 into NKT cells grown from a healthy individual. These cells are called ANCHOR cells. These cells will be infused into patients that have lymphomas or leukemias that have CD19 on their surface. The ANCHOR cells are investigational products not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of ANCHOR cells that is safe, to see how long the ANCHOR cells last, to learn what their side effects are and to see whether this therapy might help people with lymphoma or leukemia.
MEMBER ACCOUNT
登录成功会直接打开下一页。