Phase II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 TCR-Gene Engineered Lymphocytes
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Clinical Response Per the Response Evaluation Criteria in Solid Tumors (RECIST)
研究概览
简要总结
Background:
-This study uses an experimental cancer treatment that uses the patient s own lymphocytes (type of white blood cell), which are specially selected and genetically modified to target and destroy their tumor.
Objectives:
-To test the safety of the treatment and determine if it can cause the patient s tumor to shrink.
Eligibility:
- Patients greater than 18 years and less than or equal to 66 years of age whose cancer has spread beyond the original site and does not respond to standard treatment.
- Patients have tissue type human leukocyte antigen (HLA)-A*0201.
- Patients cancer cells have the ESO-1 gene.
Design:
- Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.
- Patients have leukapheresis to collect cells for laboratory treatment and later reinfusion. For this procedure, whole blood is collected thorough a tube in a vein, the desired cells are extracted from the blood, and the rest of the blood is returned to the patient.
- Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to receive the treated lymphocytes.
- Cell infusion and aldesleukin (IL-2) treatment: Patients receive the lymphocytes by a 30-minute infusion through a vein. Starting within 24 hours of the infusion, they receive high-dose aldesleukin infusions every 8 hours for up to 5 days (maximum15 doses).
- Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and aldesleukin.
- Tumor biopsy: Patients may be asked to undergo a biopsy (surgical removal of a small piece of tumor) after treatment to look at the effects of treatment on the immune cells in the tumor.
- Follow-up: After treatment is completed, patients return to the clinic once a month for several months for physical examinations, a review of side effects, laboratory tests and scans. They may undergo leukapheresis at some visits to look at the effect of treatment on the immune system and check the viability of the infused cells. Patients then return to the National Institute of Health (NIH) clinic once a year for 5 years and then complete a follow-up questionnaire for another 10 years.
- Retreatment: Patients whose tumor shrinks or disappears following treatment and then recurs may receive one additional treatment, using the same regimen of chemotherapy, lymphocyte infusion and IL-2 treatment.
详细描述
Background:
- We have constructed a single retroviral vector that contains both alpha and beta chains of a T cell receptor (TCR) that recognizes the NY-ESO-1 (ESO) tumor antigen, which can be used to mediate genetic transfer of this TCR with high efficiency (> 30%) without the need to perform any selection.
- In co-cultures with human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2) and ESO double positive tumors, anti-ESO TCR transduced T cells secreted significant amount of interferon (IFN)-gamma and additional secretion of cytokines with high specificity.
- Poxviruses encoding tumor antigens, similar to the replication-defective recombinant canarypox virus (ALVAC) ESO-1 vaccine have been shown to successfully immunize patients against these antigens.
Objectives:
Primary objectives:
- Determine if the administration of anti-ESO TCR engineered peripheral blood lymphocytes (PBL) and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic cancer that expresses the ESO antigen.
- Determine if the administration of anti-ESO TCR engineered peripheral blood lymphocytes (PBL), aldesleukin, and ALVAC ESO-1 vaccine to patients following a nonmyeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic cancer that expresses the ESO antigen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 66 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
#1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC
Patients with melanoma or renal cell cancer (RCC) will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin.
干预措施: Anti-NY ESO-1 T-cell receptor PBL (Biological)
#1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC
Patients with melanoma or renal cell cancer (RCC) will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin.
干预措施: aldesleukin (Drug)
#1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC
Patients with melanoma or renal cell cancer (RCC) will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin.
干预措施: Cyclophosphamide (Drug)
#1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC
Patients with melanoma or renal cell cancer (RCC) will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin.
干预措施: fludarabine phosphate (Drug)
#2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 TCR PBL and high dose (HD) aldesleukin
干预措施: Anti-NY ESO-1 T-cell receptor PBL (Biological)
#2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 TCR PBL and high dose (HD) aldesleukin
干预措施: aldesleukin (Drug)
#2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 TCR PBL and high dose (HD) aldesleukin
干预措施: Cyclophosphamide (Drug)
#2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 TCR PBL and high dose (HD) aldesleukin
干预措施: fludarabine phosphate (Drug)
#3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC
Patients with melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by replication-defective recombinant canarypox virus (ALVAC) NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: Anti-NY ESO-1 T-cell receptor PBL (Biological)
#3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC
Patients with melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by replication-defective recombinant canarypox virus (ALVAC) NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: aldesleukin (Drug)
#3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC
Patients with melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by replication-defective recombinant canarypox virus (ALVAC) NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: Cyclophosphamide (Drug)
#3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC
Patients with melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by replication-defective recombinant canarypox virus (ALVAC) NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: fludarabine phosphate (Drug)
#3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC
Patients with melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by replication-defective recombinant canarypox virus (ALVAC) NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: ALVAC NY ESO-1 vaccine (Biological)
#4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by ALVAC NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: Anti-NY ESO-1 T-cell receptor PBL (Biological)
#4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by ALVAC NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: aldesleukin (Drug)
#4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by ALVAC NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: Cyclophosphamide (Drug)
#4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by ALVAC NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: fludarabine phosphate (Drug)
#4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by ALVAC NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
干预措施: ALVAC NY ESO-1 vaccine (Biological)
结局指标
主要结局
Clinical Response Per the Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: Approximately 3 years
Response was determined by the RECIST. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
次要结局
- Number of Participants With In Vivo Survival of T-Cell Receptor (TCR)-Engineered Cells(1 month post treatment)
- Number of Participants With Serious and Non-Serious Adverse Events(Date treatment consent signed to date off study, approximately, 66 months and 10 days)
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Cancer Institute (NCI)