Phase I Study of Cellular Adoptive Immunotherapy Using Autologous CD4+ NY-ESO-1-Specific T Cells and Anti-CTLA4 For Patients With NY-ESO-1-Expressing Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Maximum Tolerated Dose (MTD) of Adoptively Transferred CD4 T Cells
研究概览
简要总结
The goal of this clinical research study is to learn about the safety of giving CD4+T cells with ipilimumab and cyclophosphamide.
CD4+T cells are a type of white blood cell. Researchers grow the T cells in the laboratory, and they are designed to find cancer cells and may kill them.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. The first 3 or 6 participants will receive a lower dose of ipilimumab. If there are no intolerable side effects, then the second group of 6 participants will receive a higher dose of ipilimumab.
All study participants will receive the same dose level of cyclophosphamide and the CD4+T cells.
Study Drug Administration:
You will receive cyclophosphamide by vein over about 30-60 minutes on Day -2 (2 days before you receive the CD4+T cells). If the doctor thinks it is needed, you will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.
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
- •Histopathologic documentation of melanoma, synovial sarcoma or mixed round cell liposarcoma concurrent with the diagnosis of metastatic disease.
- •Tumor expression of NY-ESO-1 (2+ staining or > 25%) by IHC.
- •Male or female subjects ≥18 years of age.
- •Expression of HLA-DPB1*0401
- •Eastern Cooperative Oncology Group (ECOG)/ Zubrod performance status of '0-1' .
- •Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. Suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion, and at least 8 weeks after the study drug is stopped. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal
- •Men must be willing and able to use an acceptable method of birth control, for at least 3 months after completion of the study, if their sexual partners are WOCBP.
- •Willing and able to give informed consent.
- •Adequate venous access - consider peripherally inserted central venous catheter (PICC) or central line
- •Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray or CT scan)
- •At least 4 weeks must have elapsed since the last chemotherapy, immunotherapy, radiotherapy, or major surgery.
- •At least 6 weeks must have elapsed since the last nitrosoureas, mitomycin C and liposomal doxorubicin
- •Toxicity related to prior therapy must either have returned to < or equal to grade 1, baseline, or been deemed irreversible
排除标准
- •Patients with active infections or oral temperature > 38.2 C within 71 hours of Leukapheresis. The procedure may be deferred.
- •Patients with Hct <30%, white blood count (WBC) <2500/uL and platelets <50,000 immediately prior to Leukapheresis. The procedure may be deferred.
- •Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix.
- •Complete blood count (CBC) and Chemistry profile prior to cyclophosphamide and T cell infusions: WBC < 2000/uL Hct < 24% or Hb < 8 g/dL absolute neutrophil count (ANC) < 1000 Platelets < 50,000 Creatinine > 3.0 x ULN AST/ALT > 2.5 x ULN Bilirubin > 3 x ULN
- •Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to entry.
- •Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with FEV1 < 2.0 L or DLco (corr for Hgb) < 75% will be excluded.
- •Significant cardiovascular abnormalities as defined by any one of the following: Congestive heart failure, Clinically significant hypotension, Symptoms of coronary artery disease, Presence of cardiac arrhythmias on EKG requiring drug therapy,Ejection fraction < 50 % (echocardiogram or MUGA).
- •Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening MRI or contrast CT).
- •Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable.
- •Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
- •Positive screening tests for HIV, Hep B, and Hep C. If positive results are not indicative of true active or chronic infection, the patient can be treated.
- •Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy.
- •Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose.
- •No prisoners or children will be enrolled on this study
研究组 & 干预措施
Ipilimumab + Cyclophosphamide + CD4+T Cells
Starting Dose of Ipilimumab 1.0 mg /kg by vein on Days 1, 22, 43, and 64. Cyclophosphamide 300 mg/m2 administered intravenously 2 days prior to T cell infusion as an outpatient procedure. Antigen-specific CD4+ T cells administered at a dose 10^10 cells/m^2.
干预措施: Ipilimumab (Drug)
Ipilimumab + Cyclophosphamide + CD4+T Cells
Starting Dose of Ipilimumab 1.0 mg /kg by vein on Days 1, 22, 43, and 64. Cyclophosphamide 300 mg/m2 administered intravenously 2 days prior to T cell infusion as an outpatient procedure. Antigen-specific CD4+ T cells administered at a dose 10^10 cells/m^2.
干预措施: Cyclophosphamide (Drug)
Ipilimumab + Cyclophosphamide + CD4+T Cells
Starting Dose of Ipilimumab 1.0 mg /kg by vein on Days 1, 22, 43, and 64. Cyclophosphamide 300 mg/m2 administered intravenously 2 days prior to T cell infusion as an outpatient procedure. Antigen-specific CD4+ T cells administered at a dose 10^10 cells/m^2.
干预措施: CD4+ T cells (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Adoptively Transferred CD4 T Cells
时间窗: 12 weeks after T cell infusion
(MTD) defined as dose level below that at which excessive toxicity was observed. Dose limiting toxicity: Any ≥ Grade 2 eye pain or reduction of visual acuity that does not respond to topical therapy and does not improve to ≤ Grade 1 severity within 2 weeks of starting therapy requires systemic treatment; Any ≥ Grade 3 bronchospasm or other hypersensitivity reaction; Any adverse event, laboratory abnormality or intercurrent illness which, in the judgment of the Investigator, presents a substantial clinical risk to the patient with continued dosing; Any other ≥ Grade 3 non-skin related adverse event.
次要结局
- Clinical Response(6 weeks after T cell infusion)