2024-516623-14-00招募中2 期
ATA129-EBV-205 An Open-label, Single-arm, Multicohort, Phase 2 Study to Assess the Efficacy and Safety of Tabelecleucel in Subjects with Epstein-Barr Virus-associated Diseases (EBVision)
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 64
- 试验地点
- 14
- 主要终点
- The ORR obtained following administration of tabelecleucel with the first two different human leukocyte antigen (HLA) restrictions
研究概览
简要总结
To determine the clinical benefit of tabelecleucel (allogeneic EpsteinBarr virus-specific cytotoxic T lymphocytes [EBV-CTLs]) in subjects with EBV-associated diseases as measured by the objective response rate (ORR)
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 主要目的
- Follow-up
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 65+ years（18-64 Years, 65+ Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •ECOG performance status ≤3 for subjects aged ≥16 years; Lansky score ≥20 for subjects from ≥1 year to <16 years
- •For subjects with CNS PTLD - R/R or newly diagnosed CNS PTLD for whom the standard first line therapy is inappropriate, as determined by the investigator, confirmed by at least 1 of the following: a.Biopsy-proven EBV+ CNS PTLD b.Positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF. Subjects with R/R disease must have had at least one prior line of systemic therapy and one of the following: a.Radiographic disease progression per Lugano Classification during or after treatment b.Failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
- •Subjects may have systemic and CNS disease, or CNS disease only meeting the following criteria: a.When present, systemic disease measurable per Lugano Classification criteria, by PET-diagnostic CT as evidenced by 18F-deoxyglucose avidity, except when contraindicated or mandated by local practice, then MRI may be used. b.CNS only disease must be measurable by MRI, CT, or by cytology and flow cytometry with EBV detected in CSF. Contrast-enhanced CT scans may be substituted in patients in whom MRI is medically contraindicated (e.g., cardiac pacemaker) or unavailable.
- •For subjects with EBV+ PTLD, where standard first line therapy (rituximab and/or chemotherapy) is inappropriate, including CD20negative disease. Biopsy-proven EBV+ PTLD for whom standard first-line therapy is inappropriate
- •Subjects must have systemic disease measurable per Lugano Classification criteria, by PET-diagnostic CT as evidenced by 18Fdeoxyglucose avidity.
- •For Subjects with sarcoma, including LMS, or smooth muscle tumors - EBV+ sarcoma or smooth muscle tumor with rapidly progressive disease defined as progressive disease per RECIST 1.1 criteria as documented radiographically within a 6-month interval prior to enrollment.
- •Biopsy-proven EBV+ sarcoma meeting one of the following criteria: a.Pathologically confirmed EBV+ Leiomyosarcoma b.EBV+ Sarcoma or smooth muscle tumor
- •Measurable disease using CT, and/or MRI following RECIST 1.1 criteria
- •Adequate organ function, unless organ dysfunction is considered to be due to the underlying EBV-associated disease
- •Males and females of any age
- •Provided written informed consent and assent, if required by law for pediatric subjects in accordance with the requirements
- •For subjects with PID LPD - Relapsed and/or refractory (R/R) or newly diagnosed PID LPD for whom the standard first line therapy is inappropriate, as determined by the investigator LPD confirmed by at least 1 of the following: a. Biopsy-proven EBV+ LPD b. Positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF Subjects with R/R disease must have had at least one prior line of systemic therapy and one of the following: a.Radiographic disease progression per Lugano Classification during or after treatment b.Failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
- •Subjects may have systemic disease only, systemic and CNS disease or CNS disease only, meeting one of the following criteria: a.Systemic disease measurable per Lugano Classification criteria, by PET-CT as evidenced by 18F-deoxyglucose avidity, except when contraindicated or mandated by local practice, then MRI may be used. b.CNS only disease measurable by MRI, CT, or by cytology and flow cytometry with EBV detected in CSF
- •For subjects with AID LPD - R/R or newly diagnosed AID LPD for whom the standard first line therapy is inappropriate, as determined by the investigator, confirmed by at least 1 of the following criteria: a.Biopsy-proven EBV+ LPD, b.Positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF Subjects with R/R disease must have had at least one prior line of systemic therapy and one of the following: a.Radiographic disease progression per Lugano Classification during or after treatment b.Failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
- •Subjects may have systemic disease only, systemic and CNS disease or CNS disease only, meeting one of the following criteria: a. Systemic disease measurable per Lugano Classification criteria, by PET-diagnostic CT as evidenced by 18F-deoxyglucose avidity b. CNS only disease measurable by MRI, CT, or by cytology and flow cytometry with EBV detected in CSF
- •For subjects with AID of idiopathic etiology or AID attributable to immunosenescence, objective laboratory evidence of immunodeficiency (e.g., lymphopenia, hypogammaglobulinemia).
排除标准
- •Currently active Burkitt, T cell, NK/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy
- •Any conditions that may put the study outcomes at undue risk: a. Life expectancy < 60 days b. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk
- •History of prior allogeneic HCT or SOT
- •Prior systemic therapy for PTLD
- •Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment, or known history of HIV infection
- •Suspected or confirmed grade ≥ 2 acute (GvHD) per the CIBMTR consensus grading system or moderate/severe chronic GvHD per NIH consensus criteria at the time of the enrollment
- •Need for vasopressor or ventilatory support at the time of enrollment
- •Prior therapy (in order of increasing washout period) prior to enrollment, as follows: a. Within 4 weeks or 5 half-lives (whichever is shorter): i. Any investigational product (co-enrollment in a non-interventional study or a study for sample collection only is permitted) ii. Any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression. B. Within 8 weeks: i. Prior tabelecleucel (>8 weeks prior to enrollment) is permitted (in consultation with the Medical Monitor) if response was obtained or if usual protocol-directed therapeutic options were not exhausted (e.g., restriction switch options) ii. Cellular therapies: chimeric antigen receptor (CAR) therapies directed at T cells or T cell subsets, donor lymphocyte infusion, other CTLs, or virus-specific T cells iii. Therapies which could impact tabelecleucel function: Anti-thymocyte globulin, alemtuzumab C. Any prior treatment with EBV-CTLs with the exception of tabelecleucel as above
- •Female who is breastfeeding or pregnant
- •Any of the following while undergoing treatment with tabelecleucel and for 90 days after the last dose (details are specified in the body of the protocol): For females of childbearing potential: 1) unwilling to use a highly effective method of contraception (i.e., one that can achieve a failure rate of less than 1% per year when used consistently and correctly) or 2) unwilling to refrain from donating eggs For males: 1) unwilling to use a condom during sexual intercourse or 2) unwilling to refrain from donating sperm or 3) has a female partner of childbearing potential who is unwilling to use a highly effective method of contraception (refer to protocol Section 5.6.4)
- •Inability or unwillingness to comply with all study procedures
- •Ongoing need for daily steroids of >0.5 mg/kg prednisone or glucocorticoid equivalent ongoing methotrexate, or extracorporeal photopheresis. For subjects with CNS disease, protocol specified dexamethasone is permitted
研究组 & 干预措施
tabelecleucel
Experimental
Participants receiving tabelecleucel
干预措施: tabelecleucel (Drug)
结局指标
主要结局
The ORR obtained following administration of tabelecleucel with the first two different human leukocyte antigen (HLA) restrictions
The ORR obtained following administration of tabelecleucel with the first two different human leukocyte antigen (HLA) restrictions
次要结局
- Progression-free survival (PFS)
- Overall survival (OS)
- Duration of response (DOR)
- For EBV-associated lymphoproliferative disease in the setting of primary imunodeficiency (EBV+ PID LPD) cohort:Number of subjects who reach definitive therapy (i.e., allogeneic HCT) for the underlying disease. Time to definitive therapy.
- For EBV+ sarcoma cohort, including leiomyosarcoma (LMS), or smooth muscle tumors: Clinical benefit rate. ORR by immune response evaluation criteria in solid tumors (iRECIST) criteria [Seymour 2017]
研究者
Pierre Fabre Medicament
Scientific
Pierre Fabre Medicament
研究点 (14)
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