Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors
Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.
연구 개요
상세 설명
In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma (n=6) will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma (n=9) and patients with other solid tumors (n=6) will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide. AdCD40L is given by weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP. A maximum of 30 patients will be included in this trial.
AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses.
연구 유형
등록 (실제)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 장소
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Uppsala, 스웨덴, 75185
- Uppsala University Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Histologically proven diagnosis of malignant solid cancer, ECOG 0-2.
- Disease progression on established treatments or patients not eligible to standard options.
- Signed informed consent must be obtained.
Exclusion Criteria:
- Pregnancy.
- Life expectancy less than 3 months.
- Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
- Patients with severe systemic autoimmune disease.
- Patients that do not consent to that tissue and blood samples are stored in a biobank.
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 |
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실험적: AdCD40L
Treatments once a week with 2.5x10e11 VP AdCD40L, maximum 4 treatments (total dose 1x10e12 VP).
If no effect in less than 2 out of 6 melanoma patients, the following 9 melanoma patients and 6 patients with other solid tumors will receive preconditioning therapy 1-2 days prior to first and last treatment with 300mg/m2 cyclophosphamid.
The next 9 melanoma patients will receive one local radiotherapy.
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Adenoviral serotype 5 vector, E1/E3 deleted.
Human CD40L gene insert driven by RSV promoter.
Vector diluted in infusion solution, 500uL solution containing 2.5x10e11 VP is intratumorally injected/treatment.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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All cause adverse events
기간: during 10 weeks
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Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.
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during 10 weeks
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Immune reactions to adenovirus and spreading of vector
기간: during 10 weeks
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Immune reactions to adenovirus will be measured by evaluating the increase of anti-adenoviral antibodies in the patients at different time points using an ELISA.
Spreading of vector will be evaluated by real time PCR to detect adenovirus vector copies in blood (plasma and erythrocyte fraction).
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during 10 weeks
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2차 결과 측정
결과 측정 |
기간 |
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Tumor burden as measured by PET/CT and whole body MR
기간: At enrollment, week 5 and week 9
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At enrollment, week 5 and week 9
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공동 작업자 및 조사자
수사관
- 연구 의자: Thomas H Tötterman, MD, PhD, Uppsala University
- 수석 연구원: Gustav Ullenhag, MD, PhD, Uppsala University Hospital
- 연구 책임자: Angelica SI Loskog, PhD, Uppsala University
간행물 및 유용한 링크
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 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 002:CD40L
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