Phase I Study Using Autologous Ex Vivo-Activated (X-ACT) Lymph Node Lymphocytes as Adoptive Immunotherapy in Advanced Malignant Melanoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Incidence of dose-limiting toxicity
研究概览
简要总结
This phase I trial studies the safety and best dose of ex-vivo activated lymph node lymphocytes (X-ACT) as well as how well the immune system responds to X-ACT treatment in participants with stage IIIC-IV melanoma. X-ACT treatment involves removing a participant's lymph node(s) close to a melanoma tumor. These lymph nodes contain special kind of cells (called T cells) which can be activated (getting the cells to start up certain responses in the immune system) outside of the body in an approved laboratory. The activated T cells are then injected back into the same participant using an i.v. to help the participant's immune system to target melanoma. The participant will undergo regular blood testing to determine whether the X-ACT treatment has resulted in changes to the immune system and also whether the T cells which were given back to the patient persist in the blood stream over time. In addition, the effect of the X-ACT treatment on the growth or shrinkage of the participant's melanoma will be measured.
详细描述
PRIMARY OBJECTIVES:
I. Assess the safety and toxicity profile of repeated infusions of ex-vivo activated tumor-draining lymphocytes (X-ACT) in participants with advanced melanoma.
SECONDARY OBJECTIVES:
I. Assess the feasibility of multiple infusions of X-ACT. II. Assess the effect of dose and schedule on immunologic parameters using two novel biomarkers.
III. Observe the clinical outcomes of participants receiving X-ACT therapy.
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
- •Participants must have a histologic diagnosis of melanoma either from a primary or metastatic site; Participants with brain metastases must have completed radiation therapy >30 days prior to enrollment
- •Participants must have American Joint Committee on Cancer (AJCC) stage IIIC unresected or IV disease
- •Patients with non-measureable or measurable disease are eligible. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter for non-nodal lesions and short axis for nodal lesions to be recorded) as ≥ 20 mm by chest x-ray, as ≥ 10 mm with CT scan, or ≥ 10 mm with calipers by clinical exam. Malignant lymph nodes, to be considered pathologically enlarged and measurable, must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis will be measured and followed.
- •Tumor lesions that are situated in a previously irradiated area can be considered measurable as long as ≥ 30 days has passed since radiation to that area
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Life expectancy (untreated) of > 4 months, in the opinion of and as documented by the investigator
- •White blood count > 3,000/mcL
- •Absolute neutrophil count > 1,200/mcL
- •Platelet count > 100,000/mcL
- •Serum creatinine < 2.0 mg/dL
- •International normalized ratio (INR) ≤ 2.0
- •In the opinion of the investigator, participant must be medically fit to undergo surgical procedure
- •Participants treated with prior chemotherapy, cytotoxic chemotherapy, radiation, biotherapy, or any investigational agent > 30 days prior to lymph node removal are eligible
- •Women of child-bearing potential must agree to use adequate contraception (double barrier method of birth control or abstinence) during participation in the study; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately
- •Participants must be disease free of prior invasive malignancies for > 5 years, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or cancer in-situ of the cervix
- •Participants must be able to understand and willing to sign a written informed consent document
- •Successful removal of melanoma-draining lymph node (MDLN)
- •ECOG Performance status ≤ 1
- •White blood count > 3,000/mcL
- •Absolute neutrophil count > 1,500/mcL
- •Platelet count > 100,000/mcL
- •Serum creatinine < 2.0 mg/dL
- •Serum direct bilirubin < 2 x institutional upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
- •Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal
- •Participants with liver metastases who do not meet the eligibility parameters may only be enrolled at the discretion of the principal investigator (PI)
排除标准
- •Participants who are taking immunosuppressive medications that cannot be discontinued (corticosteroids); participants who have discontinued immunosuppressive medications but be at least 1 week post their last dose. Patients who are taking physiologic replacement doses of corticosteroids equivalent to oral prednisone 10 mg per day will not be excluded.
- •Participants who are receiving any other investigational agents
- •Participants with a history of autoimmune disease requiring continuous treatment
- •Participants receiving any medications or substances to treat active infection
- •Pregnant or breastfeeding
- •Participants with human immunodeficiency virus (HIV) or hepatitis, or known active cytomegalovirus (CMV), Epstein-Barr virus (EBV) or any other viral illness requiring treatment are ineligible because of the potential for pharmacokinetic interactions with ACT lymph node lymphocytes
- •Any condition or behavior that in the judgment of the investigator, would compromise the participant's ability to participate in the study and/or comply with study procedures
- •Patients with bleeding disorders are ineligible due to lymph node removal possibly causing excessive bleeding. Bleeding disorder will be defined by an INR level of > 2.0
- •Step 2 None
研究组 & 干预措施
X-ACT lymph node cell dose and schedule
All patients will begin at dose level 1 and will be moved to higher dosing levels as long as the patient does not experience two or more dose limiting toxicities and maintains an acceptable performance status. A minimum of three patients will be enrolled per dose level and no patients will be enrolled on higher dose levels if dose limiting toxicities are encountered.
Dose level 1: 0.5 x 10^10 X-ACT cells. 2 infusions 4 weeks apart
Dose level 2: 1.0 x 10^10 X-ACT cells. 1 infusion
Dose level 3: 0.5 x 10^10 X-ACT cells. 4 infusions 4 weeks apart
Dose level 4: 1.0 x 10^10 X-ACT cells. 2 infusions 4 weeks apart
Dose level -1: 0.5 x 10^10 X-ACT cells. 1 infusion (if necessary)
干预措施: lymph node (Procedure)
X-ACT lymph node cell dose and schedule
All patients will begin at dose level 1 and will be moved to higher dosing levels as long as the patient does not experience two or more dose limiting toxicities and maintains an acceptable performance status. A minimum of three patients will be enrolled per dose level and no patients will be enrolled on higher dose levels if dose limiting toxicities are encountered.
Dose level 1: 0.5 x 10^10 X-ACT cells. 2 infusions 4 weeks apart
Dose level 2: 1.0 x 10^10 X-ACT cells. 1 infusion
Dose level 3: 0.5 x 10^10 X-ACT cells. 4 infusions 4 weeks apart
Dose level 4: 1.0 x 10^10 X-ACT cells. 2 infusions 4 weeks apart
Dose level -1: 0.5 x 10^10 X-ACT cells. 1 infusion (if necessary)
干预措施: X-ACT (Biological)
结局指标
主要结局
Incidence of dose-limiting toxicity
时间窗: At least 30 days after last infusion
Number of patients with dose-limiting toxicity will be reported for each treatment group. Maximum tolerated dose may be determined if dose-limiting toxicity is observed.
次要结局
- Clinical response defined by Response Evaluation Criteria In Solid Tumors 1.1(Up to 1 year)
- Prevalence of each biomarker in peripheral blood over time(Up to 1 year)