肿瘤细胞治疗研究
英文原题：MT2017-45: CAR-T Cell Therapy for Heme Malignancies
这是一项 II 期注册临床试验，评估细胞治疗用于急性淋巴细胞白血病、大 B 细胞淋巴瘤的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 150 例。试验地点：美国 · 明尼阿波利斯（共 1 个中心）。登记号：NCT03642626。
不限性别
研究评估多个FDA批准的CAR-T产品治疗血液系统恶性肿瘤；按年龄、疾病类型及既往治疗分组，分别评估各组缓解率、安全性等结局。 A组（Kymriah）和G组（Tecartus）：CD19阳性复发/难治B细胞ALL 入选标准：A组年龄0至25岁；G组年龄>18岁。疾病须为复发/难治儿童B-ALL，符合以下之一：诱导化疗至少2个疗程仍未完全缓解；至少2个巩固化疗疗程后MRD持续阳性（流式>0.01%或细胞遗传/分子检测持续阳性）；第二次或以后复发；持续CNS白血病；唐氏综合征或其他先天病且符合第二次及以后复发/难治标准；Ph+ ALL患者既往两线TKI治疗失败或不耐受，并符合第二次及以后复发/难治标准。A组Karnofsky（≥16岁）或Lansky（<16岁）评分≥50%；G组ECOG 0至2。肾功能：肌酐≤1.5×ULN或eGFR≥50 mL/min/1.73m²。肝功能：ALT≤年龄对应ULN的5倍（疾病所致升高除外）；总胆红素≤2.0 mg/dL，Gilbert综合征者总胆红素≤3.0×ULN且直接胆红素≤1.5×ULN。肺储备：呼吸困难≤1级且室内空气SpO₂>91%；血流动力学稳定，超声或MUGA显示LVEF≥45%。预期寿命≥12周。有生育能力女性及其伴侣有生育能力的男性须同意治疗期间充分避孕。研究程序前须取得成年人书面自愿同意，未成年人或能力受限成年人由父母/监护人同意。 排除：妊娠或哺乳（有生育能力女性须在登记前14天内血液或尿液妊娠检测）；Burkitt淋巴瘤/白血病（成熟B细胞ALL，表面Ig阳性且κ/λ限制、FAB L3和/或MYC易位）；CNS 2A；原发CNS淋巴瘤（CAR-T不适用）；2至4级急性或广泛慢性GVHD（单采前2周停用全部GVHD药物）；未控制的活动性乙肝或丙肝；活动性HIV；未控制、急性、危及生命的细菌/病毒/真菌感染（如输注前≤72小时血培养阳性）；CAR-T输注前1个月内不稳定心绞痛和/或心肌梗死；单采或CAR-T输注前7天内使用试验性药物；对CAR-T产品辅料不耐受；入组前至少2周停用所有免疫抑制药；或规定时限内使用方案6.1节禁止的合并用药。 B组（Yescarta）及C组（Kymriah）：复发/难治大B细胞淋巴瘤 ≥18岁；肿瘤细胞表达CD19，组织学为DLBCL非特指型、原发性纵隔大B细胞淋巴瘤、高级别B细胞淋巴瘤或滤泡性淋巴瘤转化的DLBCL。B组须化疗难治（≥2线化疗后）、≥1线挽救化疗后复发且未缓解，或自体HCT后复发并至少两线（含大剂量化疗）治疗失败；自体HCT后如接受挽救治疗，末线治疗须无应答或复发。单采时有可测量淋巴结或结外病灶。C组为≥2线系统治疗后复发/难治，或自体HCT后复发。两组ECOG 0至2、筛查（单采前）ALC≥100/μL。肾功能：肌酐≤1.5×ULN或eGFR≥50 mL/min/1.73m²；ALT≤年龄ULN的5倍（疾病所致除外）；总胆红素≤2.0 mg/dL，Gilbert综合征者总胆红素≤3×ULN且直接胆红素≤1.5×ULN；呼吸困难≤1级且室内空气SpO₂>91%；血流动力学稳定且LVEF≥45%；骨髓储备充分（骨髓受疾病浸润者除外）：ANC>1,000/mm³（仅NHL）、血小板≥50,000/mm³、血红蛋白>8.0（允许输血支持）。预期寿命≥12周；有生育能力者及其伴侣须同意治疗期间避孕；研究操作前取得书面知情同意。 B/C组排除：妊娠/哺乳；活动性CNS恶性肿瘤（脑脊液流式无病灶；CAR-T不用于原发CNS淋巴瘤）；2至4级急性或广泛慢性GVHD（单采前2周停用GVHD药物）；未控制活动性乙肝/丙肝；B组活动性HIV（控制良好的HIV可接受），C组活动或非活动HIV；未控制的急性危及生命感染；输注前1个月内不稳定心绞痛/心肌梗死；单采或输注前7天内使用试验药；对CAR-T辅料不耐受；单采前至少2周停用免疫抑制药；或规定时限内使用禁止合并用药。 D组（Tecartus/布瑞基奥仑赛）：复发/难治套细胞淋巴瘤。须接受过含蒽环类或苯达莫司汀治疗、利妥昔单抗或其他抗CD20抗体（或不适合该类药）、不适合自体HCT或自体HCT后复发，且入组时疾病活动；ECOG 0至1。肾功能：肌酐≤1.5×ULN或eGFR≥50；ALT≤年龄ULN的5倍（疾病所致除外）；总胆红素≤2 mg/dL，Gilbert综合征者总胆红素≤3×ULN且直接胆红素≤1.5×ULN；呼吸困难≤1级、室内空气SpO₂>91%、血流动力学稳定、LVEF≥45%；骨髓储备充分（疾病浸润除外）：ANC>1,000/mm³（仅NHL）、血小板≥50,000/mm³、血红蛋白>8.0（可输血）。预期寿命≥12周，有生育能力者同意避孕，并在研究程序前取得书面知情同意。排除妊娠/哺乳、活动性CNS恶性肿瘤、2至4级GVHD、未控制活动性乙/丙肝、活动性HIV、危及生命感染、输注前1个月内不稳定心绞痛/心梗、单采/输注前7天内试验药、产品辅料不耐受、单采前2周内免疫抑制剂（类固醇须在单采前>72小时停用），或规定时限内使用禁止合并药物。 E组（Breyanzi/利基迈仑赛）：≥18岁，≥2线系统治疗后复发/难治大B细胞淋巴瘤，包括DLBCL非特指型（含惰性淋巴瘤转化）、高级别B细胞淋巴瘤、原发性纵隔大B细胞淋巴瘤或3B级滤泡性淋巴瘤。ECOG 0至2；肌酐≤1.5×ULN或eGFR≥30；ALT≤年龄ULN的5倍（疾病所致除外）；总胆红素≤2 mg/dL（Gilbert综合征者总胆红素≤3×ULN且直接胆红素≤1.5×ULN）；呼吸困难≤1级、室内空气SpO₂>91%、血流动力学稳定、LVEF≥40%；骨髓储备充分（疾病浸润除外）：ANC>1,000/mm³（仅NHL）、血小板≥50,000/mm³、血红蛋白>8.0（可输血）。预期寿命≥12周、有生育能力者同意避孕，研究程序前取得知情同意。排除条件同上（妊娠/哺乳、活动CNS恶性肿瘤、2至4级GVHD、未控活动性乙/丙肝、活动HIV、危及生命感染、1个月内不稳定心绞痛/心梗、7天内试验药、产品辅料不耐受、单采前2周停免疫抑制剂且类固醇停>72小时、禁止合并用药）。 F组（Abecma/伊德卡布塔基因·维克乐）：≥18岁复发（既往部分或完全缓解后进展）或难治性多发性骨髓瘤，有活动性骨髓内或髓外疾病；既往免疫调节剂、蛋白酶体抑制剂及抗CD38单抗治疗失败或不耐受。ECOG 0至1；肌酐≤2×ULN或eGFR≥50；ALT≤年龄ULN的5倍（疾病所致除外）；总胆红素≤2 mg/dL（Gilbert综合征者总胆红素≤3×ULN且直接胆红素≤1.5×ULN）；呼吸困难≤1级、室内空气SpO₂>91%、血流动力学稳定、LVEF≥45%；骨髓储备充分（疾病浸润除外）：ANC>1,000/mm³（仅NHL）、血小板≥50,000/mm³、血红蛋白>8.0（可输血）。预期寿命≥12周，有生育能力者同意避孕，研究程序前取得知情同意。排除条件同上述CAR-T队列：妊娠/哺乳、活动CNS恶性肿瘤、2至4级GVHD、未控活动性乙/丙肝、活动HIV、危及生命感染、输注前1个月内不稳定心绞痛/心梗、单采/输注前7天内试验药、产品辅料不耐受、单采前2周内停免疫抑制药（类固醇停>72小时）及规定时限内使用禁止合并用药。
ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19
Inclusion Criteria:
* Age and Disease Status
* Must be age 0-25 years (for Arm A Kymriah) or \>18 years (Arm G Tecartus)
* Disease status: Relapsed and refractory pediatric B-cell ALL defined by one of these:
* Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy, or
* Patients with persistent minimal residual disease (MRD \>0.01% by flow cytometry or persistent by cytogenetic or molecular assays) after ≥2 cycles of consolidation chemotherapy, or
* Patients in 2nd or greater relapse of B-ALL or
* Patients with persistent CNS leukemia, or
* Down Syndrome or other congenital diseases assuming that they fit the criteria for second or greater relapse or refractory leukemia, or
* Patients with Ph+ ALL are eligible if theywho have failed or are intolerant to two lines of TKI assuming they fit the criteria for second or greater relapse or are considered refractory.
* Performance Status
\* Arm A: Karnofsky (age ≥16 years) or Lansky (age \< 16 years) performance status ≥ 50% at screening; Arm G: ECOG 0, 1 or 2
* Organ Function
* Renal function defined as:
* A serum creatinine of ≤1.5 x ULN OR
* eGFR ≥ 50 mL/min/1.73 m2
* Liver function defined as:
\*\* ALT ≤ 5 times the ULN for age (unless due to disease)
\*\* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
* Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
* Other Inclusion Criteria
* Life expectancy ≥12 weeks
* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
* Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
* Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell \[sIg positive and kappa or lambda restricted positivity\] ALL, with FAB L3 morphology and /or a MYC translocation)
* CNS 2A
* CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
* Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
* Uncontrolled active hepatitis B or hepatitis C
* Active HIV infection
* Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
* Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
* Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
* Intolerance to the excipients of the CAR-T cell product
* Any immunosuppressive medication must be stopped ≥ 2 weeks prior to enrollment.
* Patient has taken one of the prohibited concomitant medications within the timeframe outlined in section 6.1
ARM B: Yescarta for Relapsed or Refractory diffuse large B cell lymphoma
Inclusion Criteria:
* Age and Disease Status
* Adult patients (age ≥ 18 years)Patients must be ≥18 years of age
* One of the following histologies and expression of CD19 by tumor cells:
\*\* diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or
\*\* primary mediastinal large B-cell lymphoma, or
\*\* high grade B-cell lymphoma, or
\*\* DLBCL arising from follicular lymphoma
* Disease status:
\*\* Chemotherapy refractory disease after ≥2 lines of chemotherapy, or
\*\* Relapsed with no remission after ≥1 lines of salvage chemotherapy, or
\*\* Relapsed following autologous HCT (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post autoHCT, the subject must have no response or relapse after the last line of therapy
* Measurable disease at time of apheresis: Nodal lesions or extranodal lesion
* ECOG performance status 0-2
* ALC \>/=100/uL at screening (prior to apheresis)
* Renal function defined as:
\*\* A serum creatinine of ≤1.5 x ULN OR
\*\* eGFR ≥ 50 mL/min/1.73 m2
* Liver function defined as:
* ALT ≤ 5 times the ULN for age (unless due to disease)
* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
* Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
* Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
* Absolute neutrophil count (ANC) \> 1.000/mm3 (only for NHL)
* Platelets ≥ 50.000/mm3 (transfusion support can be provided)
* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
* Life expectancy ≥12 weeks
* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
* Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
* Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
* Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
* Uncontrolled active hepatitis B or hepatitis C
* Active HIV infection (controlled HIV is permissible)
* Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
* Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
* Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
* Intolerance to the excipients of the CAR-T cell product
* Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
* Patient has taken one of the prohibited concomitant medications within the timeframe.
ARM C: Kymriah for rRelapsed or rRefractory diffuse large B cell lymphoma
Inclusion Criteria:
* Age and Disease Status
* Adult patients (age ≥ 18 years)
* with relapsed or refractory (r/r) large B-cell lymphoma, including
* diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
* high grade B-cell lymphoma
* and DLBCL arising from follicular lymphoma.
* Disease status:
* after two or more lines of systemic therapy or
* relapse after autologous HCT
* Performance Status
* ECOG performance status 0-2
* ALC \>/=100/uL at screening (prior to apheresis)
* Organ Function
* Renal function defined as:
* A serum creatinine of ≤1.5 x ULN OR
* eGFR ≥ 50 mL/min/1.73 m\^2
* Liver function defined as:
* ALT ≤ 5 times the ULN for age (unless due to disease)
* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
* Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
* Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
* Absolute neutrophil count (ANC) \> 1.000/mm3 (only for NHL)
* Platelets ≥ 50.000/mm3 (transfusion support can be provided)
* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
* Other Inclusion Criteria
* Life expectancy ≥12 weeks
* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
* Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
* Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
* Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
* Uncontrolled active hepatitis B or hepatitis C
* Active or inactive HIV infection
* Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
* Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
* Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
* Intolerance to the excipients of the CAR-T cell product
* Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
* Patient has taken one of the prohibited concomitant medications within the timeframe
ARM D: Tecartus (Brexucabtagene Autoleucel) for relapsed or refractory mantle cell lymphoma
Inclusion Criteria:
* Age and Disease Status
\* with relapsed or refractory (r/r) mantle cell lymphoma, including
* prior anthracycline or Bendamustine containing therapy
* prior Rituximab or other CD20 directed antibody (or inability to treat with CD20 MoAb)
* not a candidate or relapse after autologous HCT
* active disease at enrollment
* Performance Status
\*ECOG performance status 0-1
* Organ Function
* Renal function defined as:
* A serum creatinine of ≤1.5 x ULN OR
* eGFR ≥ 50 mL/min/1.73 m2
* Liver function defined as:
* ALT ≤ 5 times the ULN for age (unless due to disease)
* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
* Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
* Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
* Absolute neutrophil count (ANC) \> 1,000/mm\^3 (only for NHL)
* Platelets ≥ 50,000/mm\^3 (transfusion support can be provided)
* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
* Life expectancy ≥12 weeks
* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
* Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
* Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
* Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
* Uncontrolled active hepatitis B or hepatitis C
* Active HIV infection
* Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
* Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
* Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
* Intolerance to the excipients of the CAR-T cell product
* Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped \>72 hours prior to apheresis).
* Patient has taken one of the prohibited concomitant medications within the timeframe
ARM E: Breyanzi "lisocabtagene maraleucel" for relapsed or refractory large B-cell lymphoma
Inclusion Criteria:
* Age and Disease Status
* Adult patients (age ≥ 18 years)
* with relapsed or refractory disease after two or more lines of systemic therapy, including
* diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma),
* high-grade B-cell lymphoma,
* primary mediastinal large B-cell lymphoma,
* follicular lymphoma grade 3B
* Performance Status
\*ECOG performance status 0-2
* Organ Function
* Renal function defined as:
* A serum creatinine of ≤1.5 x ULN OR
* eGFR ≥ 30 mL/min/1.73 m2
* Liver function defined as:
* ALT ≤ 5 times the ULN for age (unless due to disease)
* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
* Hemodynamically stable and LVEF ≥ 40% confirmed by echocardiogram or MUGA
* Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
* Absolute neutrophil count (ANC) \> 1,000/mm\^3 (only for NHL)
* Platelets ≥ 50,000/mm\^3 (transfusion support can be provided)
* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
* Life expectancy ≥12 weeks
* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
* Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
* Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
* Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
* Uncontrolled active hepatitis B or hepatitis C
* Active HIV infection
* Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
* Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
* Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
* Intolerance to the excipients of the CAR-T cell product
* Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped \>72 hours prior to apheresis).
* Patient has taken one of the prohibited concomitant medications within the timeframe
ARM F: Abecma "Idecabtagene Vicleucel" for relapsed or refractory multiple myeloma
Inclusion Criteria:
* Age and Disease Status
* Adult patients (age ≥ 18 years)
* Relapsed (progression after prior partial or complete remission) or refractory multiple myeloma
* Evidence of active disease (medullary or extramedullary)
* Prior therapy (Failure or intolerance to) with an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody
* Performance Status
\*ECOG performance status 0-1
* Organ Function
* Renal function defined as:
* A serum creatinine of ≤2 x ULN OR
* eGFR ≥ 50 mL/min/1.73 m2
* Liver function defined as:
* ALT ≤ 5 times the ULN for age (unless due to disease)
* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
* Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
* Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
* Absolute neutrophil count (ANC) \> 1,000/mm\^3 (only for NHL)
* Platelets ≥ 50,000/mm\^3 (transfusion support can be provided)
* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
* Life expectancy ≥12 weeks
* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
* Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
* Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
* Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
* Uncontrolled active hepatitis B or hepatitis C
* Active HIV infection
* Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
* Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
* Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
* Intolerance to the excipients of the CAR-T cell product
* Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped \>72 hours prior to apheresis).
* Patient has taken one of the prohibited concomitant medications within the timeframe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：Arms B & C&D& E&F: Overall Response Rate (ORR) · ORR defined by complete response + partial response by Lugano · Day 100；Arm A & E: MRD-negative CR (or CRi) · Percentage of patients with MRD-negative Complete Response CR (or CRi) · Day 28
次要终点：Percentage of Patients Developing Grade 3 or 4 ICANS；Treatment Related Mortality (TRM)；Treatment Related Mortality (TRM)；Treatment Related Mortality (TRM)；Relapse-free Survival (RFS)；Event-Free Survival (EFS)；Overall Survival (OS)；Overall Toxicity
按对应FDA批准CAR-T产品说明及本研究方案进行治疗。
按对应FDA批准CAR-T产品说明及本研究方案进行治疗。
按对应FDA批准CAR-T产品说明及本研究方案进行治疗。
按对应FDA批准CAR-T产品说明及本研究方案进行治疗。
按对应FDA批准CAR-T产品说明及本研究方案进行治疗。
按对应FDA批准CAR-T产品说明及本研究方案进行治疗。
按对应FDA批准CAR-T产品说明及本研究方案进行治疗。
本研究评估已获FDA批准的CAR-T产品治疗血液系统恶性肿瘤患者的结局。患者根据年龄和疾病分配至不同产品队列，分别计算各组缓解率、安全性事件及其他终点。
This is a phase II study of FDA-approved CAR-T products for patients with hematologic malignancies. Patients will be assigned to Arm A and B based on age and diagnosis. Overall remission rate, safety events and other endpoints will be calculated for Arm A and B separately.
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