Redirected Auto T Cells for Advanced Myeloma
A Phase I/IIa, Dual-cohort, Two-site, Clinical Trial Evaluating the Safety and Activity of Redirected Autologous T Cells Expressing a High Affinity TCR Specific for NY-ESO-1 Administered Post ASCT in Patients With Advanced Myeloma
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Maryland
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Baltimore、Maryland、美国、21201
- GSK Investigational Site
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19104
- GSK Investigational Site
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy (consisting of at least 2 treatment cycles or months of therapy)
- Myeloma has responded partially to initial therapy but a complete response (immunofixation negative and normal serum free light chain) has NOT developed after a minimum of 3 cycles or months of initial therapy
- Myeloma has high-risk features as defined by the presence of one or more cytogenetic abnormalities known to confer a poor outcome even after standard auto-transplants: complex karyotype (≥ to 3 abnormalities), t(4;14), t(14;16), del (17) (p13.1), and/or chromosome 13 abnormalities. These patients may be enrolled even while in complete or near-complete remission
- Measurable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with abnormal ratio
- Patients who are in complete remission at the time of proposed study entry (serum and urine immunofixation consistently negative and normal serum free light chains) are not eligible unless their disease meets the criteria for high-risk as defined in protocol
- Ages 18-80
- ECOG performance status 0-2 (unless due solely to bone pain)
- Prior to Lenalidomide maintenance phase, all study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®
- Females subjects of childbearing potential must have a negative pregnancy test and both male and female (of childbearing potential) subjects must agree to use reliable methods of contraception during the study.
- Lenalidomide treatment phase: able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)
- HLA-A201 patients must have confirmed expression of NY-ESO-1 and/or LAGE. HLA-A2 patients must have the A-201 allele
Adequate vital organ function as defined below:
- Serum creatinine ≤3.0 mg/dl and not on dialysis
- WBC at least 3000/mm³, platelet count at least 100,000/mm³
- SGOT ≤ to 2 x upper limit of normal and bilirubin ≤ to 2.0 mg/dl (unless due to Gilbert's syndrome)
- Left ventricular ejection fraction (LVEF) ≥ 45%. A lower LVEF is permissible if a formal cardiologic evaluation reveals no evidence for clinically significant functional impairment
- Adequate pulmonary function with mechanical parameters ≥ 40% predicted (FEV1, FVC, TLC, DLCO). Patients who are unable to complete PFTs due to bone pain or fracture must have a high resolution CT scan of the chest and must have acceptable arterial blood gases defined as a room air PO2 greater than 70 mmHg
- Patients should have recovered from any toxicities related to prior therapy or at least returned to their baseline level of organ function.
- Patients should be off of glucocorticoids for at least 2 weeks and/or other therapies for at least 1 week prior to enrollment
Exclusion Criteria:
- Pregnant or nursing females
- HIV or HTLV-1/2 seropositivity
- History of myelodysplasia
- History of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy)
- Active Hepatitis B (as defined by positive Hepatitis B surface antigen); positive Hepatitis C virus (HCV) antibody is NOT an exclusion
- Prior allogeneic transplant
- History of severe autoimmune disease requiring steroids or other immunosuppressive treatments
- Active immune mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis
- Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which would likely increase the risks of participating in the study
- Active bacterial, viral, or fungal infections
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Autologous Genetically modified T cells
Patients with advanced myeloma and who are candidates for autologous stem cell transplants, or syngeneic stem cell transplants (SSCT), will be eligible.
Prior to full screening on this study, patients will undergo prescreening to evaluate HLA-A type and presence of NY-ESO-1c259T/LAGE antigen.
Patients will undergo a steady-state mononuclear cell apheresis for T cell collection, with an optional second collection.
Once mononuclear cells have been collected, patients (or donors in the case of SSCT) will then undergo hematopoietic stem cell mobilization.
Patients will receive a dose >0.1-1 x 10¹º anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express high affinity NY-ESO-1c259 TCRs.
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Patients will undergo myeloma restaging at days +42, +100, 6 months, 9 months and 1 year post infusion. At this point, in accordance with FDA Guidelines, all patients will enter long term follow up (LTFU) and be followed biannually for monitoring for gene transfer delayed adverse events until year 5 post infusion. From year 5, all patients will require annual LTFU visits for monitoring for delayed adverse events until year 15 after receiving the genetically modified T cells. Patients whose disease progresses prior to year 1 will enter LTFU at time of progression; however these patients will be seen quarterly from progression until year 1 post infusion and then follow the LTFU schedule mentioned above. |
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Adverse Events Related to Study Treatment
大体时间:Day -40 to Year 1 post-treatment
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Number of Participants with Adverse Events related to study treatment
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Day -40 to Year 1 post-treatment
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Number of Participants With Response Per International Myeloma Working Group (IMWG) 2011 Criteria
大体时间:Change from Baseline at Day 42, 100, 180, 270 and Year 1
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Objective Response Rate (ORR) of sCR (stringent complete response), CR (complete response), VGPR (very good partial response), PR (partial response)
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Change from Baseline at Day 42, 100, 180, 270 and Year 1
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Best Objective Response (BOR)
大体时间:Best Objective Response prior to initiation of lenalidomide and at Year 1
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Number of participants with Best Objective Response of sCR, CR, VGPR, or PR
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Best Objective Response prior to initiation of lenalidomide and at Year 1
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Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS)
大体时间:DOR: Initial date of response to date of progressive disease or death PFS: Date of first T -cell infusion to earliest date of disease progression of death due to any cause OS: Date of first T-cell infusion to date of death from any cause.
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Calculated median DOR, PFS, OS
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DOR: Initial date of response to date of progressive disease or death PFS: Date of first T -cell infusion to earliest date of disease progression of death due to any cause OS: Date of first T-cell infusion to date of death from any cause.
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Peak Persistence of Modified T-cells in the Peripheral Blood
大体时间:Post-infusion through Day 42
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Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
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Post-infusion through Day 42
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Marrow Antigen Expression Pre-and Post-infusion
大体时间:Pre- and post-infusion
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Number of participants with NY-ESO-1 and LAGE or LAGE-1a expression in the marrow post-infusion
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Pre- and post-infusion
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Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells
大体时间:Post Treatment
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Number of participants with engraftment in blood and bone marrow
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Post Treatment
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 209393
- ADP 01411 (其他标识符:Adaptimmune Therapeutics)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
IPD 计划说明
IPD 共享时间框架
IPD 共享访问标准
IPD 共享支持信息类型
- 研究方案
- 树液
- 国际碳纤维联合会
- 企业社会责任
药物和器械信息、研究文件
研究美国 FDA 监管的设备产品
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