Efficacy and Safety of Allogeneic γδ T Cells (γδ T Cells) Combined With Interferon-alpha1b (IFN-α1b) or PD-1 Monoclonal Antibody in Neoadjuvant Treatment of Stage III-IV Resectable Melanoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 10
- 主要终点
- Rate of Major Pathological Response (mPR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of allogeneic γδ T cells combined with recombinant human interferon-α1b (IFN-α1b) or PD-1 monoclonal antibody in neoadjuvant treatment of patients with Stage III-IV resectable melanoma.
详细描述
This is a double-arm, single-center, randomized, open label Phase I clinical trial to evaluate the efficacy and safety of the combination of ex-vivo expanded allogeneic γδ T cells plus recombinant human interferon α1b or PD-1 monoclonal antibody in patients with Stage III-IV resectable melanoma(AJCC 8th). We randomly assigned patients with stage III-IV melanoma that was amenable to surgical resection to three doses of neoadjuvant γδT cells plus IFN-α1b or γδT cells plus pembrolizumab , surgery, and 15 doses of adjuvant γδT cells plus IFN-α1b or γδT cells plus pembrolizumab. The primary endpoints are pathological response rate after 3 cycles of treatment, including: complete pathological response rate (pCR), major pathological response rate (MPR), partial pathological response rate (pPR); preoperative imaging response rate (RECIST v1.1) was evaluated, including complete response (CR), partial response (PR), stable disease (SD), and disease progression (PD); and proportion of patients who do not need surgery due to remission. The second endpoints are event-free survival (EFS), relapse free survival (RFS), and overall survival (OS, 3 years after surgery). The safety profile of the combined γδT cells/IFN-α1b regimen and γδT cells/ pembrolizumab regimen will be monitored, we will evaluate the numbers and severity of toxicity per the Criteria for Adverse Events version 5 (CTCAEv) including but not limited to all adverse events (AE), incidence of surgery-related adverse events, and proportion of inoperable patients (due to disease progression or treatment-related adverse events).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG performance status of 0 or 1
- •Life expectancy ≥ 3 months;
- •Histologically or cytologically confirmed diagnosis of resectable stage III-IV melanoma by the American Joint Committee on Cancer (AJCC) (the 8th Edition). (Note: uveal melanoma cases are excluded)
- •Adequate organ and marrow function (within 4 weeks prior to study treatment initiation):
- •A negative urine or plasma β-HCG test result is required at screening for female patients of childbearing potential.
- •Contraception is required for patients and their partners throughout the trial and within 1 year after the last dose of study treatment.
- •Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations).
- •Be willing to signed a written informed consent document before enrollment.
排除标准
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ex-vivo expanded allogeneic γδ T cells, recombinant human interferon-α1b and PD-1 monoclonal antibody.
- •Patients accepted other anti-tumor clinical trials within 4 weeks prior to study entry.
- •Patients accepted anti-tumor radiotherapy within 4 weeks prior to study entry.
- •Disease improved by in response to anti-tumor therapies within 4 weeks including perioperative chemotherapy, molecularly targeted therapy, PD-1/PD-L1/CTLA-4 immune therapy, anti-angiogenesis therapy, interferon, herbal supplements, and other cell therapies including NK, CIK, DC, CTL and stem cell therapy etc.
- •Plan to take other systemic or local anti-tumor therapy during the current study
- •Systemic treatment with either corticosteroid (> 10 mg /kg prednisone equivalents) or other immunosuppressive medications prior to 2 weeks prior to study dose initiation
- •Known hematologic malignancy, primary brain tumor, sarcoma or any other primary solid tumor unless the disease-free period is over 5 years.
- •Imaging confirmed of central nervous system (CNS) metastases with or without meningeal carcinomatosis
- •Known severe hypersensitivity reaction of another adoptive immune cell therapy.
- •Known active autoimmune disease requiring systemic treatment (such as corticosteroids or immunosuppressive medications) or related replacement therapies (such as thyroid hormone for hypothyroidism, insulin for diabetes or physiological glucocorticoid replacement therapy for adrenal or pituitary insufficiency) in the past 2 years.
- •Surgery history within past 4 weeks, except for melanoma removal or partial removal.
- •Major organs dysfunction.
- •Acute infections and any condition has potential risk of gastrointestinal bleeding or perforation, such as active gastrointestinal ulcer, known intra luminal metastases,inflammatory bowel disease; known abdominal fistula, gastrointestinal perforation or intraperitoneal abscess 4 weeks prior to entry of the study entry.
- •Other diseases that may affect compliance or interfere with results interpretation including active opportunistic infections or progressing or severe infections , uncontrolled diabetes or pulmonary diseases including interstitial pneumonia, obstructive pulmonary disease and symptomatic bronchospasm.
- •Known HIV or AIDS-related illness, or active HBV, HCV and tuberculosis.
- •A history of getting a live vaccine within 4 weeks prior to the first dose; a history of hematopoietic stimulating factor therapy such as colony-stimulating factor (CSF) and erythropoietin (EPO) within 2 weeks prior to the first dose; a history of major surgeon except for diagnosis within 4 weeks prior to the first dose.
- •Diagnosis of a psychiatric or substance abuse disorder.
- •Individuals who are pregnant or breast-feeding or plan to conceive during the study period
- •Any other illness, laboratory abnormality, or situations that in the opinion of the principal investigator would compromise the patients' ability to tolerate treatment or would limit compliance with study requirements.
研究组 & 干预措施
group A: IFN-α1B+ γδ T cells
Stage 1: Neoadjuvant stage (Week 1-9, 3 cycles)
Stage 2: Surgical period (2 weeks, ±7 days after the last dose of neoadjuvant therapy) After multidisciplinary MDT team evaluation, the primary lesion and metastasis were resected in the corresponding departments.
Stage 3: Postoperative adjuvant period (3 weeks ±7 days -45 weeks, 15 cycles) γδ T cells administered intravenously every three weeks. Recombinant human interferon α1b administered 300μg every other day.
干预措施: Ex-vivo expanded allogeneic γδ T cells (Biological)
group A: IFN-α1B+ γδ T cells
Stage 1: Neoadjuvant stage (Week 1-9, 3 cycles)
Stage 2: Surgical period (2 weeks, ±7 days after the last dose of neoadjuvant therapy) After multidisciplinary MDT team evaluation, the primary lesion and metastasis were resected in the corresponding departments.
Stage 3: Postoperative adjuvant period (3 weeks ±7 days -45 weeks, 15 cycles) γδ T cells administered intravenously every three weeks. Recombinant human interferon α1b administered 300μg every other day.
干预措施: Recombinant human interferon α1b (Drug)
group B: Palizizumab+ γδ T cells
Stage 1: Neoadjuvant stage (Week 1-9, 3 cycles)
Stage 2: Surgical period (2 weeks, ±7 days after the last dose of neoadjuvant therapy) After multidisciplinary MDT team evaluation, the primary lesion and metastasis were resected in the corresponding departments.
Stage 3: Postoperative adjuvant period (3 weeks ±7 days -45 weeks, 15 cycles) γδ T cells administered intravenously every three weeks.Pembrolizumab administered 200mg intravenously every three weeks.
干预措施: Ex-vivo expanded allogeneic γδ T cells (Biological)
group B: Palizizumab+ γδ T cells
Stage 1: Neoadjuvant stage (Week 1-9, 3 cycles)
Stage 2: Surgical period (2 weeks, ±7 days after the last dose of neoadjuvant therapy) After multidisciplinary MDT team evaluation, the primary lesion and metastasis were resected in the corresponding departments.
Stage 3: Postoperative adjuvant period (3 weeks ±7 days -45 weeks, 15 cycles) γδ T cells administered intravenously every three weeks.Pembrolizumab administered 200mg intravenously every three weeks.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Rate of Major Pathological Response (mPR)
时间窗: at 12 weeks
Investigators will measure the rate of mPR after surgery.
Rate of Pathological Complete Response (pCR)
时间窗: at 12 weeks
Investigators will measure the rate of pCR after surgery.
Rate of Partial Pathological Response (pPR)
时间窗: at 12 weeks
Investigators will measure the rate of pPR after surgery.
Overall Response Rate(ORR)
时间窗: up to 12 weeks
ORR will be measured after neoadjuvant therapy (for participants who have measurable disease per RECIST 1.1 at start of neoadjuvant therapy).
次要结局
- Event Free survival(EFS)(From randomization up to 3 years after surgery)
- Relapse Free Survival (RFS)(After surgery up to 3 years)
- 3 Year Overall Survival (OS)(After surgery up to 3 years)
- Incidence of Adverse Events (AEs)(After surgery up to 13 months)