줄기 세포 이식 후 수지상 세포/골수종 백신과 함께 PD-1 차단
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.
연구 개요
상세 설명
- 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.
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- 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 exclusion criteria
- 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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
활성 비교기: Group 1
Monoclonal antibody CT-011 will be given 1-3 months following autologous transplant. 3 doses will be given at 6 week intervals. |
Infusions starting one to three months following autologous transplant at 6 week intervals for a total of 3 doses |
|
활성 비교기: 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. |
Infusions starting one to three months following autologous transplant at 6 week intervals for a total of 3 doses One week following each infusion of CT-011 |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
First Stage: To explore immunological response to Pidilizumab (MDV9300) in the post-transplant period.
기간: 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%. |
3 years
|
|
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.
기간: 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. |
3 years
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
First Stage: Secondary objective: To assess the toxicity associated with treating multiple myeloma patients with Pidilizumab (MDV9300)in the post-autologous transplant setting.
기간: 3 years
|
Toxicity will be monitored and will be summarized for each grade. |
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.
기간: 3 years
|
Toxicity will be monitored and will be summarized for each grade. |
3 years
|
|
To correlate levels of circulating activated and regulatory T cells with immunologic response
기간: 3 years
|
Levels of circulating activated and regulatory T cells and CD14+PD-L1+ cells will be measured at pre-transplantation, post-transplantation and several times after Pidilizumab (MDV9300) with or without vaccination. We will measure the level and the ratio of activated T cells/regulatory T cells and CD14+PD-L1+ monocytes at each time point. We will evaluate the profile of the ratio across time, several possible metrics (fold-change among successive time point) will be explored to evaluate the trend in the ratio across time. The correlation between the ratio and immunologic response (fold increase in IFNγ expression) will be assessed and reported using Spearman rank correlation at each time for 10 and 25 patients from each stage and total 35 patients from the study, by treating all measurement as continuous variables. At post-transplant time points, we will also compare the ratio of activated T cells/regulatory T cells for patients with and without significance immunologic response. |
3 years
|
|
To define anti-tumor effects using serum markers, radiological studies, and time to disease progression.
기간: 3 years
|
The percent of patients achieving a complete response (CR) following completion of therapy, including those converting from PR to CR after immunotherapy, will be reported for the phase II trial with descriptive statistics. Time to disease progression will also be characterized for with Kaplan-Meier curves. |
3 years
|
공동 작업자 및 조사자
협력자
수사관
- 수석 연구원: David Avigan, MD, Beth Israel Deaconess Medical Center
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정된)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
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