肿瘤细胞治疗研究
英文原题：Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL
这是一项 I/II 期注册临床试验，评估细胞治疗用于淋巴瘤、多发性骨髓瘤、肿瘤的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 38 例。试验地点：美国 · 教堂山（共 1 个中心）。登记号：NCT02690545。
不限性别 · ≥ 3 Years
细胞采集前纳入标准 受试者或儿科受试者的法定监护人已被告知、理解并签署知情同意书；受试者和/或法定监护人已获得一份采集用知情同意书副本 儿科受试者年龄3至17岁（体重必须≥10kg），成人受试者年龄≥18岁 受试者诊断为复发性HL或NHL，且既往治疗失败>2种方案。自体或异基因干细胞移植后复发的受试者符合本研究条件。 CD30+疾病（细胞采集时结果可待定，但在接受ATLCAR.CD30细胞治疗前必须确认）。注：CD30+疾病需要根据机构血液病理学标准，通过免疫组织化学记录CD30表达。 Karnofsky或Lansky评分>60%（≥16岁使用Karnofsky，<16岁使用Lansky） 充分的器官功能证据，定义如下： * 血红蛋白≥8.0 g/dL（入组前2周内不依赖输血） * 总胆红素≤1.5×ULN，除非归因于Gilbert综合征 * AST≤3×ULN * 血清肌酐≤1.5×ULN * 对于<18岁受试者，血清肌酐要求使用下表： 最大血清肌酐（mg/dL） 年龄（岁） 男性 女性 3至<6 ≤0.8 ≤0.8 6至<10 ≤1.0 ≤1.0 10至<13 ≤1.2 ≤1.2 13至<16 ≤1.5 ≤1.4 ≥16且<18 ≤1.7 ≤1.4 女性在采集前72小时内血清妊娠试验阴性，或记录受试者已绝经或处于月经初潮前。 有生育能力的女性（WOCBP）应愿意在研究期间及研究结束后6个月内使用2种避孕方法，或已手术绝育，或避免异性性行为。WOCBP指未手术绝育或停经未超过1年者。 • 绝经状态必须通过记录停经>1年确认。 细胞采集前排除标准 妊娠或哺乳期 肿瘤位于增大可能导致气道阻塞的部位 不得患有活动性人类免疫缺陷病毒（HIV）、乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染（细胞采集时可待定；仅符合所述标准的受试者将接受输注）。注：为符合资格，受试者需要HIV抗体阴性、乙型肝炎表面抗原阴性和HCV抗体阴性或病毒载量阴性。 淋巴细胞清除前纳入标准 受试者或儿科受试者的法定监护人已被告知、理解并签署知情同意书；受试者和/或法定监护人已获得一份知情同意书副本。 CD30+疾病（细胞采集时结果可待定，但在淋巴细胞清除前必须确认）；注：CD30+疾病需要根据机构血液病理学标准，通过免疫组织化学记录CD30表达。 在淋巴细胞清除给药前： * 中性粒细胞绝对计数（ANC）> 1.0 × 10^9/L * 血小板计数 > 75 × 10^9/L * 对于4级中性粒细胞减少、≥3级发热性中性粒细胞减少或4级血小板减少，暂停苯达莫司汀直至毒性缓解至≤2级 对于WOCBP，在淋巴细胞清除前72小时内血清妊娠试验阴性。 淋巴细胞清除前7天内（皮肤T细胞淋巴瘤受试者为30天内）的影像学结果。接受过桥接化疗的受试者必须在最近一次治疗后至少3周进行影像学检查（如果影像学检查在淋巴细胞清除前7天内，则无需重复）。 Karnofsky或Lansky评分>60%（Karnofsky用于≥16岁的儿科受试者，Lansky用于<16岁者）。 可获得符合分析证书（CofA）接受标准的自体转导活化T细胞。 有生育能力的女性（WOCBP）应愿意在研究期间及研究结束后6个月内使用2种避孕方法，或已手术绝育，或避免异性性行为。WOCBP是指未进行手术绝育或未停经>1年者。 淋巴细胞清除前排除标准 在细胞输注前六周内接受过任何研究性药物或任何肿瘤疫苗。 在细胞输注前4周内接受过抗CD30抗体为基础的治疗。 在淋巴细胞清除前3周内接受过化疗。 根据治疗肿瘤科医生的判断，受试者患有快速进展性疾病。 根据治疗肿瘤科医生的判断，受试者不是CAR T细胞治疗的合适候选者。 妊娠或哺乳期。 肿瘤位于增大可能导致气道阻塞的部位。 当前使用剂量相当于每日≥10mg泼尼松或等效剂量的全身性皮质类固醇；接受每日<10mg者可根据研究者判断入组。允许使用吸入性类固醇。 对于儿科受试者，允许使用剂量为6-12 mg/m2/天的生理替代氢化可的松。根据研究者判断，允许使用等效剂量的替代类固醇，但不得超过每日10mg泼尼松。允许使用吸入性类固醇。 正在使用CYP1A2强抑制剂（如氟伏沙明、环丙沙星）的受试者，因为这些药物可能增加苯达莫司汀的血浆浓度，并降低其代谢产物的血浆浓度。CYP1A2强抑制剂的最新列表见http://medicine.iupui.edu/clinpharm/ddis/。详情见方案。（这适用于接受苯达莫司汀用于淋巴细胞清除（必需）的受试者，直至苯达莫司汀末次给药后72小时。） HIV、HBV或HCV活动性感染（细胞采集时可为待定状态；仅符合所述标准的受试者将接受输注。受试者需HIV抗体阴性或乙型肝炎表面抗原阴性且HCV抗体阴性或病毒载量阴性。 乙型肝炎：乙型肝炎表面抗原阳性的受试者被排除。乙型肝炎表面抗原阴性但乙型肝炎核心抗体阳性的受试者必须检查其乙型肝炎病毒载量。如果这些受试者在基线时病毒载量为阳性，则将被排除。核心抗体阳性且基线时病毒载量阴性的受试者，如果受试者在淋巴细胞清除前已开始抗HBV预防方案，则将被视为合格。 ATLCAR.CD30细胞输注前纳入标准 以下定义的器官功能充分证据： * 总胆红素 ≤1.5 × ULN，除非归因于Gilbert综合征 * AST ≤3 × ULN * 血清肌酐 ≤1.5 × ULN * 室内空气下脉搏血氧饱和度 >90% * 对于<18岁的受试者，血清肌酐要求使用下表： 最大血清肌酐（mg/dL） 年龄（岁） 男性 女性 3至<6 ≤0.8 ≤0.8 6至<10 ≤1.0 ≤1.0 10至<13 ≤1.2 ≤1.2 13至<16 ≤1.5 ≤1.4 ≥16且<18 ≤1.7 ≤1.4 Karnofsky或Lansky评分 >60%（≥16岁用Karnofsky，<16岁用Lansky） 可获得符合分析证书（CofA）接受标准的自体转导活化T细胞。 有生育潜力的女性（WOCBP）应愿意在研究期间及研究结束后6个月内使用2种避孕方法或已手术绝育，或避免异性性行为。WOCBP是指未手术绝育或未停经>1年的女性。 ATLCAR.CD30细胞输注前排除标准 在细胞输注前六周内接受过任何研究性药物或任何肿瘤疫苗。 在细胞输注前4周内接受过基于抗CD30抗体的治疗。 肿瘤位于增大可能导致气道阻塞的部位。 根据治疗肿瘤科医生的判断，受试者患有快速进展性疾病。 根据治疗肿瘤科医生的判断，受试者不是CAR T细胞治疗的良好候选者。 当前使用全身性皮质类固醇，剂量≥10 mg泼尼松/天或等效剂量；接受<10 mg/天者可由研究者酌情入组。允许使用吸入性类固醇。对于儿科受试者，允许使用剂量为6-12mg/m2/天的生理替代性氢化可的松。经研究者酌情决定，允许使用等效剂量的替代类固醇，但不得超过10mg泼尼松/天。允许使用吸入性类固醇。 HIV或HCV活动性感染（细胞采集时可待定；仅符合所述标准的受试者将接受输注）。受试者要求HIV阴性、乙型肝炎表面抗原阴性，且HCV抗体阴性或病毒载量阴性。 乙型肝炎：乙型肝炎表面抗原阳性的受试者被排除。乙型肝炎表面抗原阴性但乙型肝炎核心抗体阳性的受试者必须检查其乙型肝炎病毒载量。如果这些受试者在基线时病毒载量为阳性，则将被排除。核心抗体阳性且基线时病毒载量阴性的受试者将被视为合格。这些受试者必须在淋巴细胞清除前开始接受抗病毒预防治疗。 第二次输注前淋巴细胞清除的资格标准（可选）注：如果受试者在输注时符合资格标准，但不符合充分骨髓功能和血小板计数的资格要求，则可在未进行淋巴细胞清除的情况下接受第二次输注。 Karnofsky或Lansky评分>60%（Karnofsky用于≥16岁，Lansky用于<16岁）。 WOCBP必须愿意在研究期间或研究结束后6个月内使用2种避孕方法，或已手术绝育，或避免异性性行为。WOCBP是指未进行手术绝育或未停经>1年者。 受试者在输注前7天内不得怀孕或哺乳。 不得有位于增大可能导致气道阻塞部位的肿瘤。 受试者必须在淋巴细胞清除前30天内具有确认活动性疾病的影像学结果，但皮肤淋巴瘤受试者除外，如果基线扫描显示基线时淋巴结≤1.5cm，则无需在第二次细胞输注前重复扫描。 不得当前使用全身性皮质类固醇，剂量≥10 mg泼尼松/天或等效剂量；接受<10mg/天者可由研究者酌情入组 以下定义的充分器官功能证据： * ANC>1.0 × 10^9/L * 血小板>75 × 10^9/L * 总胆红素≤1.5 × ULN，除非归因于Gilbert综合征 * AST ≤3 × ULN * 血清肌酐≤1.5 × ULN * 室内空气下脉搏血氧饱和度>90% * 对于<18岁的受试者，血清肌酐要求使用下表： 最大血清肌酐（mg/dL） 年龄（岁） 男性 女性 3至<6 ≤0.8 ≤0.8 6至<10 ≤1.0 ≤1.0 10至<13 ≤1.2 ≤1.2 13至<16 ≤1.5 ≤1.4 ≥16且<18 ≤1.7 ≤1.4 淋巴细胞清除前72小时内血清妊娠试验阴性，或记录显示受试者已绝经。绝经状态必须通过记录显示无月经>1年或记录显示涉及双侧卵巢切除术的手术绝经来确认。 受试者不得使用CYP1A2的强抑制剂（例如氟伏沙明、环丙沙星），因为这些药物可能增加苯达莫司汀的血浆浓度，并降低其代谢物的血浆浓度。参见http://medicine.iupui.edu/clinpharm/ddis/获取CYP1A2强抑制剂的最新列表。（这适用于接受苯达莫司汀进行淋巴细胞清除（必需）的受试者，直至苯达莫司汀末次给药后72小时） 根据研究者的判断，受试者是ATLCAR.CD30治疗的良好候选者。 第二次输注前的资格标准（可选） 无未控制感染或脓毒症的证据。 受试者在第二次输注前不得接受过桥接化疗（或方案未强制要求的其他抗癌治疗）。 器官功能充足的证据，定义如下： * 总胆红素≤2×ULN，除非归因于Gilbert综合征 * AST≤3×ULN * ALT≤3×ULN * 血清肌酐≤1.5×ULN * 室内空气下脉搏血氧饱和度>90% * 对于<18岁的受试者，使用下表确定血清肌酐要求： 最大血清肌酐（mg/dL） 年龄（岁） 男性 女性 3至<6 ≤0.8 ≤0.8 6至<10 ≤1.0 ≤1.0 10至<13 ≤1.2 ≤1.2 13至<16 ≤1.5 ≤1.4 ≥16且<18 ≤1.7 ≤1.4 根据治疗医师的意见，受试者无快速进展性疾病的临床指征 根据研究者的判断，受试者是ATLCAR.CD30治疗的良好候选者。 如果受试者在基线时乙型肝炎核心抗体检测呈阳性，则自基线检测以来不得出现乙型肝炎病毒再激活。 受试者在输注后7天内不得怀孕或哺乳。
Inclusion Criteria Prior to Cell Procurement Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guradian given a copy of informed consent form for procurement Ages 3 to 17 years of age for pediatric subjects (weight must be ≥10kg), and for adults ages ≥18 years of age Diagnosis of recurrent HL or NHL in subjects who have failed \>2 prior treatment regimens. Subjects relapsed after autologous or allogeneic stem cell transplant are eligible for this study. CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with ATLCAR.CD30 cells). NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard. Karnofsky or Lansky score of \>60% (Karnofsky for ≥16 years old and Lansky for \<16 years old) Evidence of adequate organ function as defined by: * Hemoglobin ≥ 8.0 g/dL (transfusion independent for 2 weeks prior to enrollment) * Total bilirubin ≤ 1.5 × ULN, unless attributed to Gilbert's Syndrome * AST ≤ 3 × ULN * Serum creatinine ≤ 1.5 × ULN * For subjects \<18 years old use the following table for serum creatinine requirements: Maximum Serum Creatinine (mg/dL) Age (years) Male Female 3 to \<6 ≤0.8 ≤0.8 6 to \<10 ≤1.0 ≤1.0 10 to \<13 ≤1.2 ≤1.2 13 to \<16 ≤1.5 ≤1.4 ≥16 and \<18 ≤1.7 ≤1.4 Negative serum pregnancy test in females within 72 hours prior to procurement or documentation that the subject is post-menopausal or premenarchal. Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for \>1 year. • Postmenopausal status must be confirmed with documentation of absence of menses for \>1 year. Exclusion Criteria Prior to Cell Procurement Pregnant or lactating Tumor in a location where enlargement could cause airway obstruction Must not have an Active infection with human immunodeficiency virus (HIV), Hepatitis B Virus (HBV))or, Hepatitis C virus (HCV) (can be pending at the time of cell procurement; only subjects meeting the criteria as so described will be infused). Note: To meet eligibility subjects are required to have negative HIV antibody, negative for Hepatitis B surface antigen and negative for HCV antibody or viral load. Inclusion Criteria Prior to Lymphodepletion Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guradian given a copy of informed consent form. CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to lymphodepletion); Note: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard. Prior to administration of lymphodepletion: * Absolute neutrophil count (ANC) is \> 1.0 × 10\^9/L * Platelet count \> 75 × 10\^9/L * For Grade 4 neutropenia, Grade ≥3 febrile neutropenia, or Grade 4 thrombocytopenia, hold bendamustine until toxicity resolve to Grade ≤2 For WOCBP negative serum pregnancy test within 72 hours prior to lymphodepletion. Imaging results from within 7 days (30 days in subjects with cutaneous T cell lymphoma) prior to lymphodepletion. Subjects who have received bridging chemotherapy must have imaging performed at least 3 weeks after most recent therapy (imaging does not need to be repeated if it is within 7 days prior to lymphodepletion). Karnofsky or Lansky score of \>60% (Karnofsky for pediatric subjects ≥16 years old and Lansky for \<16 years old). Available autologous transduced activated T cells that meet the Certificate of Analysis (CofA) acceptance criteria. Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for \> 1 year. Exclusion Criteria Prior to Lymphodepletion Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion. Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell infusion. Received chemotherapy within the previous 3 weeks prior to lymphodepletion. Subject has rapidly progressive disease, per treating oncologist's discretion. Subject is not a good candidate for CAR T cell therapy, per treating oncologist's discretion. Pregnant or lactating. Tumor in a location where enlargement could cause airway obstruction. Current use of systemic corticosteroids at doses equivalent of ≥10mg prednisone daily or its equivalent; those receiving \<10mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed. For pediatric subjects, physiologic replacement hydrocortisone at doses 6-12 mg/m2/day is allowed. Equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10mg prednisone per day. Inhaled steroids are allowed. Subjects on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as these may increase plasma concentrations of bendamustine, and decrease plasma concentrations of its metabolites. See http://medicine.iupui.edu/clinpharm/ddis/ for an updated list of strong inhibitors of CYP1A2. Details are given in the protocol.(This applies to subjects who receive bendamustine for lymphodepletion (required) up through 72 hours after the last dose of bendamustine.) Active infection with HIV, HBV or HCV (can be pending at the time of cell procurement; only subjects meeting the criteria as so described will be infused. Subjects are required to have negative HIV antibody or negative for Hepatitis B surface antigen and negative HCV antibody or viral load. Hepatitis B: Subjects who are positive for Hepatitis B Surface Antigen are excluded. Subjects who are Hepatitis B Surface Antigen negative but hepatitis B core Antibody positive must have their hepatitis B viral load checked. These subjects will be excluded if their viral load is positive at baseline. Subjects who are core antibody positive and viral load negative at baseline will be considered eligible if the subject has initiated an anti-HBV prophylaxis regimen prior to lymphodepletion. Inclusion Criteria Prior to Infusion of ATLCAR.CD30 Cells Evidence of adequate organ function as defined by: * Total bilirubin ≤1.5 × ULN, unless attributed to Gilbert's Syndrome * AST ≤3 × ULN * Serum creatinine ≤1.5 × ULN * Pulse oximetry of \>90% on room air * For subjects \<18 years old use following table for serum creatinine requirements: Maximum Serum Creatinine (mg/dL) Age (years) Male Female 3 to \<6 ≤0.8 ≤0.8 6 to \<10 ≤1.0 ≤1.0 10 to \<13 ≤1.2 ≤1.2 13 to \<16 ≤1.5 ≤1.4 ≥16 and \<18 ≤1.7 ≤1.4 Karnofsky or Lansky score of \>60% (Karnofsky for ≥16 years old and Lansky for \<16 years old) Available autologous transduced activated T cells that meet the Certificate of Analysis (CofA) acceptance criteria. Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for \> 1 year. Exclusion Criteria Prior to Infusion of ATLCAR.CD30 Cells Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion. Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell infusion. Tumor in a location where enlargement could cause airway obstruction. Subject has rapidly progressive disease, per treating oncologist's discretion. Subject is not a good candidate for CAR T cell therapy, per treating oncologist's discretion. Current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving \<10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed For pediatric subjects, physiologic replacement hydrocortisone at doses 6-12mg/m2/day is allowed. Equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10mg prednisone per day. Inhaled steroids are allowed. Active infection with HIV or HCV (can be pending at the time of cell procurement; only subjects meeting the criteria as so described will be infused). Subjects are required to be negative for HIV and negative for Hepatitis B surface antigen, and negative HCV antibody or viral load. Hepatitis B: Subjects who are positive for Hepatitis B Surface Antigen are excluded. Subjects who are Hepatitis B Surface Antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked. These subjects will be excluded if their viral load is positive at baseline. Subjects who are core antibody positive and viral load negative at baseline will be considered eligible. These subjects must be receiving antiviral prophylaxis initiated prior to lymphodepletion. Eligibility Criteria Prior to Lymphodepletion for Second Infusion (Optional) Note: Subjects may receive a second infusion without prior lymphodepletion if they meet the eligibility criteria at the time of infusion, but do not meet the eligibility requirements for adequate bone marrow function and platelet counts. Karnofsky or Lansky score of \>60% (Karnofsky for ≥16 years old and Lansky for \<16 years old). WOCBP must be willing to use 2 methods of birth control or be surgically sterile , or abstain from heterosexual activity for the course of the study, or for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for \> 1 year. Subject must not be pregnant or lactating within 7 days of infusion. Must not have tumor in a location where enlargement could cause airway obstruction. Subjects must have imaging results confirming active disease from within 30 days prior to lymphodepletion with the exception of cutaneous lymphoma subjects who do not need to repeat scans prior to the second cell infusion if the baseline scans showed lymph nodes ≤ 1.5cm at baseline. Must not have current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving \<10mg daily may be enrolled at discretion of the Investigator Evidence of adequate organ function as defined by: * ANC\>1.0 × 10\^9/L * Platelets \>75 × 10\^9/L * Total bilirubin ≤1.5 × ULN, unless attributed to Gilbert's syndrome * AST ≤3 × ULN * Serum creatinine ≤1.5 × ULN * Pulse oximetry of \> 90% on room air * For subjects \<18 years old use following table for serum creatinine requirements: Maximum Serum Creatinine (mg/dL) Age (years) Male Female 3 to \<6 ≤0.8 ≤0.8 6 to \<10 ≤1.0 ≤1.0 10 to \<13 ≤1.2 ≤1.2 13 to \<16 ≤1.5 ≤1.4 ≥16 and \<18 ≤1.7 ≤1.4 Negative serum pregnancy test within 72 hours prior to lymphodepletion or documentation that the subject is post-menopausal. Post-menopausal status must be confirmed with documentation of absence of menses for \> 1 year or documentation of surgical menopause involving bilateral oophorectomy. Subject cannot be on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as these may increase plasma concentrations of bendamustine, and decrease plasma concentrations of its metabolites. See http://medicine.iupui.edu/clinpharm/ddis/ for an updated list of strong inhibitors of CYP1A2. (This applies to subjects who receive bendamustine for lymphodepletion (required) up through 72 hours after the last dose of bendamustine) Subject is a good candidate for treatment with ATLCAR.CD30 per the investigator's discretion. Eligibility Criteria Prior to Second Infusion (Optional) No evidence of uncontrolled infection or sepsis. Subject must not have undergone bridging chemotherapy (or other anti-cancer therapies, which are not mandated by the protocol) prior to the second infusion. Evidence of adequate organ function as defined by: * Total bilirubin ≤2 × ULN, unless attributed to Gilbert's syndrome * AST ≤3 × ULN * ALT ≤3 × ULN * Serum creatinine ≤1.5 × ULN * Pulse oximetry of \>90% on room air * For subjects \<18 years old use following table for serum creatinine requirements: Maximum Serum Creatinine (mg/dL) Age (years) Male Female 3 to \<6 ≤0.8 ≤0.8 6 to \<10 ≤1.0 ≤1.0 10 to \<13 ≤1.2 ≤1.2 13 to \<16 ≤1.5 ≤1.4 ≥16 and \<18 ≤1.7 ≤1.4 Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician Subject is a good candidate for treatment with ATLCAR.CD30 per the investigator's discretion. If subjects have had positive hepatitis B core antibody testing at baseline, they must not have had re-activation of the Hepatitis B virus since baseline testing. Subject must not be pregnant or lactating within 7 days of infusion.
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：Number of participants with adverse events as a measure of safety and tolerability of ATLCAR.CD30 cells to establish a safe dose after lymphodepletion with bendamustine in adult patients · Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE · 6 weeks；Number of participants with adverse events as a measure of safety and tolerability of ATLCAR.CD30 cells to establish a safe dose after lymphodepletion after lymphodepletion with bendamustine and fludarabine in pediatric patients · Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE · 6 weeks；2 year progression free survival (PFS) after administration of ATLCAR.CD30 in combined adult/pediatric patients with CD30+ refractory/relapsed HL and NHL. · PFS is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a results of any cause per the Lugano classification. · 2 years
次要终点：2 year overall survival (OS) after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.；2 year overall survival (OS) after administration of ATLCAR.CD30 transduced ATl following lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed HL and NHL；2 year progression free survival after administration of ATLCAR.CD30 following lymphodepletion with bendamustine in adult patients with CD30+ in adult patients with CD30+ refractory/relapsed HL and NHL.；2 year progression free survival after administration of ATLCAR.CD30 following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ refractory/relapsed HL and NHL.；Objective response rate as defined by the Lugano Classification for CAR.CD30 transduced ATL following lymphodepletion with bendamustine when administered in adult patients with CD30+ relapsed/refractory HL and NHL；Objective response rate as defined by the Lugano classification for CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.；Duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL.；Duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.
Ib 期：在成人中，并单独在儿童中，将研究两种剂量：1x10^8 cells/m2 和 2x10^8 cells/m^2。研究团队将运行两个独立的剂量递增序列，一个用于成人，另一个用于儿童。研究团队计划采用 3+3 设计，并从低剂量 1x10^8 cells/m2 开始。如果前 3 名患者没有 DLT，研究团队将升至 2 x 10^8 cells/m2 的剂量。如果初始队列中有 1/3 患者出现毒性，研究团队将扩大入组至最多 6 名患者。如果在 2 x 10^8 cells/m^2 剂量下出现剂量限制性毒性（DLT），研究团队将最初将剂量降至中间剂量 1.5 x 10^8 cells/m^。 II 期：研究团队计划入组 31 名患者以提供数据。将使用序贯边界监测 DLT 发生率。
人体有多种对抗感染和疾病的方式。似乎没有一种方式能完美地对抗癌症。这项研究结合了两种不同的对抗疾病的方式：抗体和T细胞。抗体是保护人体免受细菌或有毒物质引起的疾病的蛋白质。抗体通过结合这些细菌或物质来发挥作用，从而阻止它们生长并造成不良影响。T细胞，也称为T淋巴细胞，是特殊的抗感染血细胞，能够杀死其他细胞，包括肿瘤细胞或受感染的细胞。抗体和T细胞都已被用于治疗癌症患者。它们都显示出了前景，但单独使用任何一种都不足以治愈大多数患者。本研究旨在将T细胞和抗体结合起来，创建一种更有效的治疗方法，称为靶向CD30抗原的自体T淋巴细胞嵌合抗原受体细胞（ATLCAR.CD30）给药。 在先前的研究中，已表明可以将一种新基因导入T细胞，从而增强其识别和杀死癌细胞的能力。本研究中导入T细胞的新基因可产生一种称为抗CD30的抗体。这种抗体由于淋巴瘤细胞外部一种称为CD30的物质而附着于淋巴瘤细胞。抗CD30抗体已被用于治疗淋巴瘤患者，但强度不足以治愈大多数患者。在本研究中，抗CD30抗体已被改变，使其不再游离于血液中，而是与T细胞结合。当抗体以这种方式与T细胞结合时，被称为嵌合受体。这些CD30嵌合（组合）受体激活的T细胞似乎能杀死部分肿瘤，但它们在体内存活时间不长，因此其对抗癌症的机会尚不明确。 这项研究的目的在于确定在淋巴细胞清除性化疗后输注ATLCAR.CD30细胞的安全剂量，并估计在ATLCAR.CD30给药后两年内癌症未进展的患者人数。本研究还将观察ATLCAR.CD30细胞的其他效果，包括其对患者癌症的影响。
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration. In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown. The purpose of this research study is to establish a safe dose of ATLCAR.CD30 cells to infuse after lymphodepleting chemotherapy and to estimate the number patients whose cancer does not progress for two years after ATLCAR.CD30 administration. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on the patient's cancer.
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