NCT05835687进行中（未招募）1 期
Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.
Primary objectives
- To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).
Secondary objectives
- To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).
- To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).
详细描述
Treatment on this study includes four (4) B7-H3-CAR T cell infusions over a 4 week period. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter without lymphodepleting chemotherapy. The study will evaluate the safety and maximum tolerated dose (MTD) of B7-H3-CAR T cells using a 3+3 study design and a 4 week evaluation period. Follow up will occur on this protocol for 1 year after the final B7-H3-CAR T cell infusion and then continue on an institutional long-term follow up protocol to complete 15 years post-infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screening Eligibility
- •Age ≤ 21 years of age
- •Primary CNS tumor
- •For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor
- •For Cohort B, must meet one of the following criteria:
- •Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry [IHC] or H3K27M mutation if pontine lesion)
- •Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M)
- •Has presumptive/suspected brainstem high-grade neoplasm with available imaging for central imaging review
- •Life expectancy of > 12 weeks
- •Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
排除标准
- •Screening Eligibility All Participants
- •1. Participant has other clinically significant medical disorders (e.g. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with study procedure.
- •Inclusion Criteria: Procurement and T-cell Production Eligibility
- •Age ≤ 21 years of age
- •Primary CNS tumor with measurable or evaluable disease and meets criteria for either Cohort A or B:
- •Cohort A: relapsed/refractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive
- •Cohort B: Diffuse midline glioma AND tumor is:
- •B7-H3 positive if non-pontine
- •OR H3K27-altered diffuse midline pontine glioma
- •OR radiographically-confirmed classic/typical DIPG
- •Estimated life expectancy of >12 weeks
- •Karnofsky or Lansky performance score ≥50
- •Participant of childbearing/child-fathering potential agrees to use contraception
- •For females of childbearing age:
- •Not pregnant with negative serum pregnancy test
- •Not lactating with intent to breastfeed
- •Chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment
- •The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment
- •At least 30 days from most recent cell infusion prior to enrollment.
- •All systemically administered corticosteroid therapy must be stable or decreasing for ≥1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m^2/day
- •Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program
- •Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
- •Exclusion Criteria: Procurement and T-cell Production Eligibility
- •Known primary immunodeficiency or acquired immunodeficiency.
- •Known HIV positivity
- •Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection).
- •Rapidly progressive disease
- •Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments.
- •Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study.
- •Inclusion Criteria: Treatment Eligibility
- •Relapsed/refractory non-brainstem CNS primary tumor
- •Tumor must be considered B7-H3 positive
- •Diffuse Midline Glioma - Must meet one of the following criteria
- •Tumor is considered B7-H3 positive
- •H3K27-altered diffuse midline pontine glioma
- •Radiographically-confirmed classic/typical DIPG
- •Must complete standard radiation prior to Loc3CAR treatment and be a minimum of 6 weeks post-completion of radiation therapy
- •All participants
- •Age ≤ 21 years old
- •Primary CNS tumor with measurable or evaluable disease
- •Available autologous T-cell product that has met GMP release criteria
- •Participant has a CNS reservoir catheter (e.g., Ommaya) or programmable shunt
- •First CAR T cell infusion is planned/scheduled ≥ 5 days from CNS surgery, including catheter placement
- •The following treatments must be discontinued for the specified duration prior to treatment enrollment:
- •Radiation therapy: ≥ 6 weeks
- •Bevacizumab: ≥ 28 days
- •Cytotoxic chemotherapy: ≥ 21 days
- •Biologic agents: ≥ 7 days
- •Antibody therapy: ≥ 3 half-lives or 30 days (whichever is shorter)
- •Cellular therapy: ≥ 30 days
- 另有 34 项未显示
研究组 & 干预措施
Arm A (relapsed/refractory CNS tumors)
Experimental
Patients with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors.
干预措施: B7-H3-CAR T cells (Drug)
Arm B (diffuse midline gliomas [DMG])
Experimental
Patients with DMG.
干预措施: B7-H3-CAR T cells (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Four (4) weeks after the first B7-H3-CAR T-cell infusion or 7 days after the fourth B7-H3-CAR T cell infusion, whichever is longer
To determine the maximum tolerated dose for the locoregional delivery of autologous B7-H3-CAR T cells in patients with recurrent/refractory B7-H3- positive primary CNS tumors (Cohort A) or diffuse midline glioma (DMG) (Cohort B).
次要结局
- Radiographic response(Four (4) weeks post B7-H3-CAR T-cell infusion)
研究者
研究点 (1)
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