A Pilot Study Testing Intralesional Injection of Ex-Vivo Expanded Allogenic University Donor (UD) NK and TGFBi NK Cells in Patients With Cutaneous Keratinocyte Carcinomas
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Change in intratumoral natural killer (NK) cell content
研究概览
简要总结
This early phase I trial compares the safety, side effects and the biological or cellular activity of two types of universal donor (UD) natural killer (NK) cells (standard NK cells and transforming growth factor [TGF] beta imprinted [TGF-beta-i] NK cells), given directly into the tumor (intratumoral) in treating patients with skin (cutaneous) squamous cell carcinoma (SCC) or basal cell carcinoma (BCC). NK cells are a type of white blood cell that can recognize missing or incorrect proteins on tumor cells and then kill these tumor cells. It was recently discovered that infection with human cytomegalovirus (CMV), a common virus, leads to the development of a unique NK cell population. These "adaptive" NK cells have a more potent anti-tumor killing action. The TGF-beta-i NK cells used in this study are created using donors whose blood tests positive for CMV exposure. This may make them more effective at killing tumor cells. Giving UD TGF-beta-i NK cells may be safe, tolerable and/or more effective than standard UD expanded NK cells in treating patients with SCC or BCC.
详细描述
PRIMARY OBJECTIVE:
I. To determine the persistence of NK cell infiltration within biopsy-proven keratinocyte carcinomas following intra-tumoral injection of universal donor NK cells versus (vs) TGFbeta-resistant NK cells in a cohort of patients prior to their standard of care excision.
SECONDARY OBJECTIVES:
I. To assess the tolerability of NK cell cutaneous intra-tumoral injection measured by adverse events, described using Common Terminology for Cancer Related Adverse Events (CTCAE version [v] 5).
II. To test the feasibility of a larger study using intra-tumorally injected NK cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Ohio State University patients > 18 years old
- •Diagnosis of ≥ 1cm keratinocyte carcinoma, accessible by intra-tumoral injection
- •Confirmation of cutaneous SCC (cSCC) (10 patients total) or BCC (10 patients total) via diagnostic biopsy
- •BCC: Nodular or aggressive subtype
- •SCC: Well-differentiated or aggressive subtype with T1 or T2 staging by American Joint Committee on Cancer (AJCC) criteria
- •Patient meets criteria for standard of care surgical treatment with either wide local excision or Moh's surgery
- •Presence of residual clinical cancer ≥ 1cm at the time of baseline
- •Willingness to follow up for residual cancer extirpation between 2-8 weeks after the injection
排除标准
- •Planned or concurrent radiation or systemic treatment for solid tumor or hematologic malignancy including chemotherapies or immunotherapies received within 6 weeks of trial enrollment. These include but are not limited to methotrexate, 5-fluorouracil, vismodegib, cepilimumab, pembrolizumab, nivolumab, ipilimumab for any skin malignancy
- •< 18 years old
- •A negative deep and peripheral margin status from the diagnostic biopsy
- •Diagnostic biopsy with the following histopathologic characteristics:
- •BCC: Superficial subtype
- •SCC: SCC in situ (SCCIS)/Bowen disease, basosquamous, keratoacanthoma (KA)-type SCC, or tumor with > T2 staging by AJCC criteria
- •Any skin disease or active infection in the same area that may confound assessments
- •Inability to follow-up for definitive treatment (surgical excision)
- •Any other comorbidity or complication that in the opinion of the investigator could make the patient unsafe to participate in the study, such as:
- •Active infection
- •Pregnant women, women who are likely to become pregnant or are breastfeeding
- •Patients who received any other investigational drugs within the 30 days prior to screening visit
研究组 & 干预措施
Cohort I (UD expanded NK cells)
Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
干预措施: Biopsy Procedure (Procedure)
Cohort I (UD expanded NK cells)
Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
干预措施: Surgical Procedure (Procedure)
Cohort II (UD expanded TGFbetai NK cells)
Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded TGF-beta-i NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
干预措施: Biopsy Procedure (Procedure)
Cohort II (UD expanded TGFbetai NK cells)
Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded TGF-beta-i NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
干预措施: Surgical Procedure (Procedure)
Cohort II (UD expanded TGFbetai NK cells)
Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded TGF-beta-i NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
干预措施: Universal Donor Expanded TGF-beta-imprinted NK Cells (Biological)
Cohort I (UD expanded NK cells)
Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
干预措施: Natural Killer Cell Therapy (Biological)
结局指标
主要结局
Change in intratumoral natural killer (NK) cell content
时间窗: Up to 2 weeks after locoregional injection of NK cells
Immunohistochemical and in vitro studies of tissue from the original biopsy and post-NK cell treated tumor specimens will be performed to assess NK cell infiltration of the tumor. Difference in NK cell density by CD56 staining in pre- versus post-intervention skin tumor tissue will be compared between tumors receiving NK versus transforming growth factor betai cell injections.
次要结局
- Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events version 5.0 criteria(Up to 8 weeks after biopsy)
研究者
Brittany Dulmage
Principal Investigator
Ohio State University Comprehensive Cancer Center