Vaccine Enriched, Autologous, Activated T-Cells Directed to Tumor in Patients With Relapsed/Refractory Melanoma (MARVSmALo)
Phase I Study of Vaccine Enriched, Autologous, Activated T-Cells Redirected to the Tumor Marker GD2 in Patients With Relapsed/Refractory Melanoma
연구 개요
상세 설명
The rate of progression free survival at one (1) year is < 20% for patients with stage IV metastatic melanoma, despite aggressive cytotoxic chemotherapy regimens and newly approved immunomodulatory and targeted therapy. Immunotherapy seems to hold the most promise for achieving prolonged survival or even cure, therefore,efforts have focused on several different approaches. Such approaches have used tumor vaccination, adoptive transfer of tumor infiltrating lymphocytes, and even monoclonal antibodies, unconjugated or conjugated to cytokines, toxins, or radionucleotides.
The tumor-associated antigen GD2 has been noted on the surface of several tumors, most notably neuroblastoma, but is expressed on melanoma as well. Clinical studies have shown activity of a GD2-specific chimeric T-cell receptor expressed on activated, autologous, T-cells in patients with neuroblastoma. It is the investigators intention to enrich peripheral blood mononuclear cells (PBMC) of patients with stage IV metastatic melanoma with vaccine-specific T-cells through pre-harvest/ phlebotomy vaccination with common, well understood vaccines. The investigators will then modify the T-cells to attack the GD2 antigen. These tumor redirected, vaccine specific, activated T-cells will then be infused into the patient following revaccination with the common vaccines. The Investigators will monitor expansion of the modified T-cells through serial polymerase chain reaction (PCR) assays following vaccination.
The Investigators then intend to re-vaccinate with the selected vaccines one month following infusion and monitor for expansion of the modified T-cells.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
-
-
Kansas
-
Fairway, Kansas, 미국, 66205
- KU Cancer Center
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Metastatic, surgically unresectable melanoma or newly diagnosed melanoma of any stage, where the patient is unable to receive or complete standard therapy
- Life expectancy of at least 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
Laboratory Values
- absolute neutrophil count > 500 microliters (mcL)
- platelet > 50,000 mcL
- serum aspartate aminotransferase (AST) < 5 x institutional upper limit of normal (IULN)
- total bilirubin < 3 x IULN
- serum creatinine < 3 x IULN
- Pulse oximetry of > 95% on room air.
- Must have recovered from the toxic effects of all prior chemotherapy
Exclusion Criteria:
- Patients with rapidly progressive disease.
- Patient is currently receiving any investigational drugs
- Current cardiomegaly or bilateral pulmonary infiltrates on chest radiograph, pulmonary metastatic lesions are allowed
- Patients must not have tumor in a location where enlargement could cause airway obstruction
- Patient is pregnant or lactating
- History of hypersensitivity reactions to murine protein-containing products.
- Currently receiving immunosuppressive drugs such as corticosteroids (excluding topical treatment), tacrolimus or cyclosporin
- Received any tumor vaccines within previous six weeks
- Known hypersensitivity to rat monoclonal antibodies
- History of severe allergic reaction to Hepatitis B vaccine, Polio vaccine or Tetanus, Diphtheria, Pertussis vaccine (DTP, Tdap, DT or Td).
- Allergy to baker's yeast or other components of the vaccines.
- History of allergy to the antibiotics Neomycin, Streptomycin or Polymyxin B
- History of coma, long/multiple seizures within 7 days after DTP or Tdap, unless a cause other than the vaccine was indicated.
- Melanoma involvement of the central nervous system
- Chemotherapy given within the last 28 days
- Presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: tvs-CTL Vaccine
Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells.
|
autologous, 14g2a.zeta
chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL)
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Measurement of infusion related adverse events to evaluate the safety of infused T-cells
기간: 4 weeks
|
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
|
4 weeks
|
|
PCR measurement of retroviral construct to measure persistence of infused T-cells
기간: 4 weeks
|
To evaluate how long the infused T-cells remain in the blood stream
|
4 weeks
|
|
Measurement of replication competent retrovirus to evaluate the safety of infused T-cells
기간: 4 weeks
|
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
|
4 weeks
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
PCR measurement of retroviral construct to measure the expansion of infused T-cells
기간: 12 months
|
To determine the expansion of infused tvs-CTL in response to repeat vaccination with previously administered vaccines
|
12 months
|
|
PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination
기간: 12 months
|
To compare the frequency of tvs-CTL in the peripheral blood, after revaccination, to the frequency noted in the prior study of autologous activated, CAR-transduced T-cells infused in patients with relapsed, refractory Stage IV melanoma
|
12 months
|
|
Imaging studies to measure tumor response
기간: 10 weeks
|
Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.
|
10 weeks
|
공동 작업자 및 조사자
스폰서
수사관
- 수석 연구원: Gary Doolittle, MD, University of Kansas Medical Center
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- Mel-2012-01-01
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .