Study of Administration of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors and Containing the Inducible Caspase 9 Safety Switch in Subjects With Triple Negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Toxicity: Cytokine Release Syndrome (CRS)
研究概览
简要总结
This phase 1, single-center, open-label study explores the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells in subjects with relapsed/refractory triple-negative breast cancer (TNBC).
详细描述
T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (iC9-CAR.B7-H3 T cells) treatment is experimental and has not been approved by the Food and Drug Administration. The safety of iC9-CAR.B7-H3 T cells will be investigated using a modified 3+3 design. The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided based on the maximum tolerated dose (MTD) and additional factors such as the ability to manufacture sufficient cells for infusion.
Subjects with TNBC who meet procurement eligibility criteria will have cells collected to manufacture iC9-CAR.B7-H3 T cells. Eligible subjects will receive lymphodepletion with cyclophosphamide and fludarabine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Unless otherwise noted, subjects must meet all of the following criteria to participate in in all phases of the study:
- •Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative.
- •Age ≥ 18 years at the time of consent.
- •Karnofsky score of > 60% (see APPENDIX VI- Karnofsky Scale))
- •Histologically confirmed TNBC (ER-, PR-, HER2-negative)
- •ER- and PR-negative: defined as < 1% staining by immunohistochemistry (IHC)
- •HER2-negative: defined as IHC 0-1+ or fluorescence in situ hybridization (FISH) ratio < 2.0
排除标准
- •Patients with a history of symptomatic CNS involvement or multiple metastases requiring whole-brain radiation.
- •Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- •Subject does not have a measurable and or evaluable disease as defined by RECIST 1.1
研究组 & 干预措施
iC9-CAR.B7-H3 T cells
Specimen will be collected to prepare the iC9-CAR.B7-H3 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9-CAR.B7-H3 T cells. In part 2, the iC9-CAR.B7-H3 T cells are given by infusion after completion of lymphodepletion chemotherapy.
干预措施: cyclophosphamide (Drug)
iC9-CAR.B7-H3 T cells
Specimen will be collected to prepare the iC9-CAR.B7-H3 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9-CAR.B7-H3 T cells. In part 2, the iC9-CAR.B7-H3 T cells are given by infusion after completion of lymphodepletion chemotherapy.
干预措施: iC9-CAR.B7-H3 T Cell Therapy (Biological)
iC9-CAR.B7-H3 T cells
Specimen will be collected to prepare the iC9-CAR.B7-H3 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9-CAR.B7-H3 T cells. In part 2, the iC9-CAR.B7-H3 T cells are given by infusion after completion of lymphodepletion chemotherapy.
干预措施: fludarabine (Drug)
结局指标
主要结局
Toxicity: Cytokine Release Syndrome (CRS)
时间窗: Up to 8 weeks after infusion of Biological/Vaccine
CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38\^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death
Toxicity: Immune effector cell-associated neurotoxicity syndrome (ICANS)
时间窗: Up to 4 weeks
Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria. Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).
Toxicity: NCI-CTCAE
时间窗: Up to 4 weeks
Toxicity will be graded as the Number of participants with adverse events (AE)s AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
次要结局
- The recommended phase 2 dose (RP2D) CRS Grading(Up to 4 weeks)
- The recommended phase 2 dose (RP2D)(Up to 4 weeks)
- Progression Free Survival (PFS)(Up to 2 years)
- The recommended phase 2 dose (RP2D) NCI-CTCAE v5.(Up to 4 weeks)
- Objective response rate(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)
- Duration of Response (DOR)(Up to 2 years)