肿瘤细胞治疗研究
英文原题：Personalized NK Cell Therapy in CBT
这是一项 II 期注册临床试验，评估异体NK 细胞治疗白血病、急性淋巴细胞白血病、急性髓系白血病的安全性、可行性及初步疗效。当前状态：招募中。计划入组 100 例。试验地点：美国 · 休斯顿（共 1 个中心）。登记号：NCT02727803。
不限性别 · ≥ 15 Years 且 ≤ 80 Years
纳入标准： • 患有以下血液系统恶性肿瘤之一：急性髓系白血病（AML），包括诱导治疗失败、首次缓解期但复发风险高（中危或高危细胞遗传学特征，如复杂核型、异常[abn][3q]、−5/5q−、−7/7q−、abn[12p]、abn[17p]、髓系/淋巴系或混合谱系白血病[MLL]基因重排、t(6;9)、FLT3突变阳性和/或流式细胞术提示微小残留病）；既往化疗后继发白血病和/或由骨髓增生异常综合征（MDS）演变的白血病；或首次缓解后疾病进展。 • MDS：原发性或治疗相关，包括考虑接受移植者，并符合以下任一项：修订版国际预后评分系统（IPSS）中危或高危组；输血依赖；低甲基化药物治疗无应答或疾病进展；伴原始细胞过多的难治性贫血；转化为急性白血病；慢性粒单核细胞白血病；非典型MDS/骨髓增殖性疾病；复杂核型、abn(3q)、−5/5q−、−7/7q−、abn(12p)或abn(17p)。 • 急性淋巴细胞白血病（ALL）：诱导治疗失败、原发难治（首个疗程后未达完全缓解）、已超过首次缓解（包括第二次或更后续缓解）或存在活动性疾病。首次缓解患者若属高危也可入组，高危定义为任何时间检测到t(9;22)或t(4;11)、低二倍体、复杂核型、细胞毒药物暴露后继发白血病、微小残留病，或急性双表型白血病或双打击非霍奇金淋巴瘤。 • 非霍奇金淋巴瘤（NHL）：处于第二或第三次完全缓解，或复发（包括自体造血干细胞移植后复发）；复发性双打击淋巴瘤可入组。已知存在可治愈治疗方案者不符合条件。 • 小淋巴细胞淋巴瘤（SLL）或慢性淋巴细胞白血病（CLL）：至少接受两线标准治疗后疾病进展。 • 慢性髓性白血病（CML）第二慢性期或加速期。 • 霍奇金病（HD）：诱导治疗失败、首次完全缓解后、复发（包括自体造血干细胞移植后复发）或存在活动性疾病。 • 多发性骨髓瘤：II或III期、有症状且分泌型，需要治疗。 • 已确定可作为植入失败备用细胞来源的人员（如单倍型相合家庭成员）或脐带血单位。 • 年龄要求：清髓方案1为15–45岁；非清髓方案2为15–80岁（由研究者酌情决定）；减低强度方案3适用于15–80岁且研究者认为不适合清髓治疗者。 • Karnofsky评分≥60%。 • LVEF：清髓方案1及减低强度方案3要求≥40%；非清髓方案2要求≥30%。 • 肺功能检查（PFT）显示按血红蛋白浓度校正的DLCO≥预计值的50%（清髓方案1及减低强度方案3）。 • 血清肌酐在正常范围；若高于正常范围，肾功能（实测或估算肌酐清除率或GFR）须>40 mL/min/1.73 m²。 • SGPT/胆红素：清髓方案1及减低强度方案3要求<正常值的2倍；非清髓方案2要求<正常值的4倍。 • 有生育能力女性（定义为未绝经12个月）β-hCG妊娠试验阴性。 • 已知有可治愈治疗方案者不符合条件。 • 本研究受试者经PI酌情批准，可参加其他支持治疗研究性新药（IND）研究。 排除标准： • HIV阳性；通过核酸检测确定HIV状态。 • 未控制的严重疾病，如充分抗生素治疗后仍持续败血症、接受心脏药物治疗仍失代偿的充血性心力衰竭、需要插管的肺功能不全（拟接受脐带血移植的原发疾病所致者除外），或妨碍知情同意的精神状况。 • 有CNS恶性肿瘤史且目前存在活动性CNS疾病。 • 有合适且愿意捐献的HLA相合亲缘供者。
Inclusion Criteria: * Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics including complex karyotype, abnormal \[abn\]\[3q\], -5/5q-, -7/7q-, abn\[12p\], abn\[17p\], myeloid/lymphoid or mixed-lineage leukemia \[MLL\] gene re-arrangement and t \[6;9\]47, fms related tyrosine kinase 3 \[flt3\] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndromes (MDS), any disease beyond first remission * Myelodysplastic syndrome (MDS): Primary or therapy related, including patients that will be considered for transplant; these include any of the following categories: 1) revised International Prognostic Scoring System (IPSS) intermediate and high risk groups, 2) malondialdehyde (MDA) with transfusion dependency, 3) failure to respond or progression of disease on hypomethylating agents, 4) refractory anemia with excess of blasts, 5) transformation to acute leukemia, 6) chronic myelomonocytic leukemia, 7) atypical MDS/myeloproliferative syndromes, 8) complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p) * Acute lymphoblastic leukemia (ALL): Induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma * Non-Hodgkin's lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); relapsed double hit lymphomas; patients with options for treatment that are known to be curative are not eligible * Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following a minimum of two lines of standard therapy * Chronic myeloid leukemia (CML) second chronic phase or accelerated phase * Hodgkin's disease (HD): Induction failures, after first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease * Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment * A person (such as a haploidentical family member) or unit of cord blood must be identified as a source of back-up cells source in case of engraftment failure * Patient age criteria: age \>= 15 and =\< 45 years (myeloablative regimen 1; age \>= 15 and =\< 80 years (nonmyeloablative regimen 2) at the discretion of the investigator(s); age \>= 15 and =\< 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy may receive reduced intensity regimen 3 * Performance score of at least 60% by Karnofsky * Left ventricular ejection fraction of at least 40% (myeloablative regimen 1, reduced intensity regimen 3) * Left ventricular ejection fraction of at least 30% (nonmyeloablative regimen 2) * Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration (myeloablative regimen 1, reduced intensity regimen 3) * Serum creatinine within normal range, or if serum creatinine outside normal range, then renal function (measured or estimated creatinine clearance or glomerular filtration rate \[GFR\]) \> 40mL/min/1.73 m\^2 * Serum glutamate pyruvate transaminase (SGPT)/bilirubin \< to 2.0 x normal (myeloablative regimen 1), reduced intensity regimen 3; SGPT/bilirubin \< to 4.0 x normal (nonmyeloablative regimen 2) * Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months * Patients with options for treatment that are known to be curative are not eligible * Patients enrolled in this study may be enrolled on other supportive care investigational new drug (IND) studies at the discretion of the principal investigator (PI) Exclusion Criteria: * Human immunodeficiency virus (HIV) positive; HIV results will be determined by nucleic acid testing * Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which cord blood \[CB\] transplantation is proposed), or psychiatric condition that would limit informed consent * Active central nervous system (CNS) disease in patient with history of CNS malignancy * Availability of appropriate, willing, human leukocyte antigen (HLA)-matched related stem cell donor
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：Progression free survival (PFS) time in C2C2 patients · Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, human leukocyte antigen (HLA) match, cytomegalovirus (CMV) status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling. · From the date of engraftment to disease progression or death, assessed up to 4 years；Progression free survival (PFS) time in C1 patients · Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling. · From the date of cord blood transplant to disease progression or death, assessed up to 4 years
次要终点：Overall survival time；Incidence of transplant related mortality；Incidence of graft-versus host disease；Incidence of infection
患者在第−9、−8日接受抗胸腺细胞球蛋白静脉输注，每次4小时；第−7至−4日接受磷酸氟达拉滨静脉输注（1小时）、氯法拉滨静脉输注（1小时）及白消安静脉输注（3小时）；第−3日接受全身照射（TBI）。 脐带血移植：第0日接受脐带血移植。 NK细胞输注：第30至180日期间静脉输注NK细胞，每次30分钟。
CD20阳性恶性肿瘤患者于第−9日接受利妥昔单抗静脉输注（6小时）。患者于第−8、−7日接受抗胸腺细胞球蛋白静脉输注（各4小时）；第−6至−3日接受磷酸氟达拉滨静脉输注（各1小时）；第−6日接受环磷酰胺静脉输注（3小时）；研究者可酌情决定第−1日是否进行TBI。 脐带血移植：第0日接受脐带血移植。 NK细胞输注：第30至180日期间静脉输注NK细胞，每次30分钟。
患者于第−7、−6日接受抗胸腺细胞球蛋白静脉输注（各4小时）；第−5至−2日接受磷酸氟达拉滨静脉输注（各1小时）；第−2日接受美法仑静脉输注（30分钟）。 脐带血移植：第0日接受脐带血移植。 NK细胞输注：第30至180日期间静脉输注NK细胞，每次30分钟。
这项II期临床试验研究化疗和脐带血移植后个体化自然杀伤（NK）细胞治疗骨髓增生异常综合征、白血病、淋巴瘤或多发性骨髓瘤患者的效果。试验将根据HLA-KIR分型，为HLA-C1/x受者筛选脐带血（CB），并为HLA-C2/C2患者采用脐带血来源NK细胞进行过继治疗。NK细胞可能杀伤化疗后残留于体内的肿瘤细胞，并降低脐带血移植后发生移植物抗宿主病的风险。
This phase II clinical trial studies how well personalized natural killer (NK) cell therapy works after chemotherapy and umbilical cord blood transplant in treating patients with myelodysplastic syndrome, leukemia, lymphoma or multiple myeloma. This clinical trial will test cord blood (CB) selection for human leukocyte antigen (HLA)-C1/x recipients based on HLA-killer-cell immunoglobulin-like receptor (KIR) typing, and adoptive therapy with CB-derived NK cells for HLA-C2/C2 patients. Natural killer cells may kill tumor cells that remain in the body after chemotherapy treatment and lessen the risk of graft versus host disease after cord blood transplant.
MEMBER ACCOUNT
登录成功会直接打开下一页。
