Blockade of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 3
- 主要终点
- First Stage: To explore immunological response to CT-011 in the post transplant period.
研究概览
简要总结
The purpose of this research study is to determine the safety of CT-011 alone, as well as the combination of the Dendritic cell fusion vaccine and CT-011, after autologous stem cell transplantation (ASCT). We are also trying to find out what effect the combination has on the disease, including if it is more successful in preventing or delaying the disease from coming back, compared to treatment with autologous transplantation alone. ASCT is a standard therapy for multiple myeloma that is often successful in significantly decreasing the amount of cancer in the body. CT-011 is an investigational monoclonal antibody. Monoclonal antibodies are a type of drug given by infusion into a vein and are known to target specific cells (in this case, cells in the immune system). The dendritic cell fusion vaccine is an investigational agent that tries to help the immune system to recognize and fight against cancer cells. Unlike a standard vaccine that is used to prevent infections, cancer vaccines are being studied to see if they can fight cancers that are already in the body.
详细描述
- There are two groups in this study: Group 1: All participants in this study group will receive infusions of CT-011 starting one to three months following autologous transplant. Participants in this group will receive a total of 3 doses of CT-011 at 6 week intervals. Group 2: All participants in this group will receive infusions of CT-011 starting one to three months following autologous transplant. Participants in this group will receive a total of 3 doses of CT-011 at 6 week intervals. In addition, they will receive a vaccination of the Dendritic Cell Fusion Vaccine one week following each infusion of CT-011.
- All participants (Group 1 and Group 2) will receive the following procedures: 1) Initial therapy for multiple myeloma: All participants will receive standard therapy to reduce the number of multiple myeloma cells in the body. 2) Prior to stem cell mobilization participants will undergo a physical exam, medical history, and blood tests to measure blood counts, liver and kidney function, multiple myeloma protein level, and research testing to measure the immune response against the multiple myeloma cells. A small amount of bone marrow will be removed from the participants hip. Participants will also undergo a skin test called "delayed-type hypersensitivity (DTH). 3) Prior to the autologous stem cell transplant, we will harvest stem cells from the participants blood and store then for the future transplant through a process called leukapheresis. 4) Within a few weeks of successful stem cell collection, participants will be admitted to the hospital for high dose chemotherapy with autologous stem cell transplantation (ASCT). 5) Approximately 1-3 months following ASCT, participants will undergo additional tests to assess their eligibility to proceed with treatment with CT-011 alone (group 1) or the combination of CT-011 and vaccination (group 2).
- If the post-transplant eligibility results meet the study requirements participants will receive 3 infusions of CT-011 at 6 week intervals. Prior to each infusion of CT-011, participants will undergo the following procedures: blood tests, urine sample, physical exam and EKG. Participants will be seen weekly to review any side effects, what medications they are taking, and will have a blood test an physical exam.
- For Group 2 participants only: Prior to autologous transplant, Group 2 participants will undergo several procedures to make the Dendritic Cell Fusion Vaccine. 1) Dendritic Cell Collection via leukapheresis 2) Tumor cell collection from the participants bone marrow. One week after receiving the CT-011 infusion, Group 2 participants will receive the study vaccine for a total of 3 vaccines.
- After the final treatment both Group 1 and Group 2 participants will receive a tumor DTH injection and DTH to Candida into the skin. At one, three and six months following the last study treatment participants will have blood tests, urine test, bone marrow aspirate/biopsy and a skeletal survey. At two, four and five months, participants will have a blood test.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with multiple myeloma who are potential candidates for high doses chemotherapy with stem cell rescue
- •Patients must not have active of history of autoimmune disorders/conditions including Type I diabetes, Type II diabetes, vitiligo or stable hypothyroidism will not be considered
排除标准
- •Patients with measurable disease as defined by a history of an elevated M component in plasma, urine, or free kappa/lambda light chains in the serum
- •18 years of age or older
- •ECOG Performance Status of 0-1 with a greater than nine week life expectancy
- •>20% bone marrow involvement in plasmacytoma amenable to resection under local anesthesia
- •Negative pregnancy test and adequate contraception method(s)
- •DLCO (adjusted) > 50%
- •Cardiac Ejection Fraction > 45%
- •Laboratory results as defined in protocol
- •Exclusion Criteria:
- •History of clinically significant venous thromboembolism
- •Clinically significant autoimmune disease
- •HIV positive
- •Serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
- •Pregnant or lactating women
- •History of allogeneic bone marrow/stem cell transplant
研究组 & 干预措施
Group 1
Monoclonal antibody CT-011 will be given 1-3 months following autologous transplant. 3 doses will be given at 6 week intervals.
干预措施: CT-011 (Drug)
Group 2
Vaccination with DC/myeloma fusion cells will be given 1-3 months following autologous transplant. Vaccination will be given at 6 weeks intervals. The monoclonal antibody CT-011 will be given 1 week following each vaccination. 3 doses of CT-011 will be given at 6 week intervals.
干预措施: Dendritic Cell Fusion Vaccine (Biological)
Group 2
Vaccination with DC/myeloma fusion cells will be given 1-3 months following autologous transplant. Vaccination will be given at 6 weeks intervals. The monoclonal antibody CT-011 will be given 1 week following each vaccination. 3 doses of CT-011 will be given at 6 week intervals.
干预措施: CT-011 (Drug)
结局指标
主要结局
First Stage: To explore immunological response to CT-011 in the post transplant period.
时间窗: 3 years
Second Stage: To determine if cellular immunity is induced by treatment with monoclonal antibody CT-011 and DC/myeloma fusion cells in conjunction with stem cell transplant.
时间窗: 3 years
First Stage: To explore immunological response to Pidilizumab (MDV9300) in the post-transplant period.
时间窗: 3 years
Immune response will be measured by assessing percentage of T cells that express IFNγ following ex-vivo exposure to tumor lysate, as determined by the ratio of the maximum IFNγ expression to the baseline level pre-transplantation. A threshold response of a 10 fold increase in T cells expressing IFNγ will be considered significant. In the pilot phase, summary statistics (mean, median, range, standard error) will be used to report immunologic response on the entire patient cohort. In order to increase precision and provide more information about the immunologic response, the original sample size of 10 patients for the pilot study was increased up to 20. With 20 patients on this stage, the 90% C.I. will be no wider than 39.7%.
Second Stage: To determine if cellular immunity is induced by treatment with monoclonal antibody Pidilizumab (MDV9300)and DC/myeloma fusion cells in conjunction with stem cell transplant.
时间窗: 3 years
Cellular immunity will be determined by measuring fold increase in IFNγ expression. The combination of vaccination and Pidilizumab (MDV9300) will be considered promising if the study shows evidence of at least 75% patients with \>10-fold increase in IFNγ expression, and would not be considered promising if \>10-fold increase is observed in 50% or less patients. With total n=25 patients, the combination will be considered promising for further study if 17 or more patients demonstrate significant immune response.
次要结局
- First Stage: To assess the toxicity associated with treating multiple myeloma patients with CT-011 in the post- autologous transplant setting.(3 years)
- Second Stage: To define anti-tumor effects using serum markers, radiological studies, and time to progression.(3 years)
- Second Stage: To correlate levels of circulating activated and regulatory T cells with immunologic response(3 years)
- Second Stage: To assess the toxicity associated with treating multiple myeloma patients with the combination with DC/myeloma fusion vaccine following autologous transplant.(3 years)
- First Stage: Secondary objective: To assess the toxicity associated with treating multiple myeloma patients with Pidilizumab (MDV9300)in the post-autologous transplant setting.(3 years)
- To correlate levels of circulating activated and regulatory T cells with immunologic response(3 years)
- To define anti-tumor effects using serum markers, radiological studies, and time to disease progression.(3 years)
研究者
David Avigan
Principal Investigator
Beth Israel Deaconess Medical Center