- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT02921373
Tracking Peripheral Blood Mononuclear Cells With Fluorine MRI (TRACK)
A Phase I Study Evaluating the Feasibility of Using Fluorine-19 Cell Sense to Image Human Peripheral Blood Mononuclear Cells In Vivo
연구 개요
상태
상세 설명
Background: None of the currently available Good Manufacturing Practices (GMP)-grade MRI cell labelling agents are approved for use in Canada. There is one iron oxide nanoparticle GMP grade preparation that is commercially available but it is not suitable for labelling the immune cell populations the investigators are interested in tracking in vivo. The investigators have, instead, chosen to develop the commercially available, GMP-grade 19F-based perfluorocarbon, known as Cell Sense, for the purpose of tracking immune cell-based vaccine therapies in vivo. This agent has been successful used in a phase I clinical trial in United States and is approved for a second trial current recruiting, under the oversight of the FDA.
The cell tracing agent Cell Sense (CS-1000) is an inert, non-metabolizable tracer. As CS-1000 is taken-up and incorporated into the cell traditional pharmacodynamic and pharmacokinetic analyses in animals and humans are not appropriate, as adsorption and biodistribution will vary with cell type, and therefore have not been done. In vitro studies of toxicity towards various cell types did not yield evidence of adverse effects on various cell functions. Cell Sense also was shown to be non-mutagenic using the Ames and Forward thymidine kinase (TK) assays. Some limited skin irritation was observed when >2,500 fold more Cell Sense than expected to be maximally injected into humans was injected intradermally into rats.
Examples of MRI cell tracking labels include superparamagnetic iron oxide nanoparticles and 19F-containing compounds such as perfluorocarbons. The advantage of using cellular MRI to track cells is that a non-radioactive tracer is used that is suitable for longitudinal studies. MRI offers 3D imaging with exquisite soft tissue contrast. The additional advantage of using 19F over iron-based agents is that 19F is a positive, easily quantifiable contrast cell labelling agent. Furthermore, there is no 19F-background MRI signal in humans whereas MRI involving iron can be confounded by different imaging artifacts and it is a negative contrast agent that is difficult to accurately quantify. The investigators are particularly interested in whether immune cells arrive in secondary lymphoid organs such as lymph nodes.
Study Design:
Open label, dose escalating, single centre, phase I study that will accrue (a) 6 healthy adults and (b) 6 prostate cancer patients.
Three healthy adults and three prostate cancer patients will be enrolled into the first cohort. Whole blood (150 ml) will be obtained by venipuncture. After processing of the blood to obtain peripheral blood mononuclear cells (PBMC), half of the PBMC will be treated with Cell Sense for 8-24 hours. Given the robustness of our data using 5 donors during dry runs, the investigators do not propose to compare labeled vs unlabeled cells as release criteria. However, the investigators will be collecting this data for information and research purposes. Three million (3 x 106) Cell Sense labeled autologous PBMC will be administered intradermally to the cohort 1 subjects. The three healthy adults and the 3 prostate cancer subjects will be tested concurrently.
If no grade 2 or higher adverse events are observed with the 1st cohort, concurrent enrolment will proceed to recruit a second set of 3 healthy adult subjects and the second set of 3 prostate cancer patients. The second cohort of subjects will be subjected to the same design but with an escalation of the dose to 2-3 x 107 Cell Sense-labeled autologous PBMC administered intradermally.
Endpoints:
Primary Endpoints:
Determine the feasibility of using Cell Sense to detect and monitor the migration of PBMC in humans
Secondary Endpoints:
- Confirm and further optimize the 19F Cell Sense detection and Hydrogen- 1 (1H) anatomical imaging parameters for imaging using the 19F/1H dual coil.
- Determine if Cell Sense-labeled PBMC migration to the draining lymph node can be detected.
- Determine if the lymph nodes in the area of interest imaged change in size on the injected side compared to the contralateral side.
- Quantify the number of Cell Sense-labeled PBMC detected.
- Evaluate safety parameters (toxicity) as defined by:
- adverse events.
- serious adverse events.
- changes in laboratory determination and vital sign parameters as assessed by medical history, physical examination and clinical laboratory tests.
The following categories will be used to grade any adverse events:
- Grade 1: does not interfere with daily activity,
- Grade 2: interferes with daily activity, no treatment required, except paracetamol,
- Grade 3: prevents daily activity or requires treatment.
- Grade 4: Life-threatening
NIH and FDA (or CTCAE v 4.0) guidelines will be used to determine the severity of adverse events
연구 유형
등록 (예상)
단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Gregory A Dekaban, PhD
- 전화번호: 24241 519-931-5777
- 이메일: dekaban@robarts.ca
연구 연락처 백업
- 이름: Paula J Foster, PhD
- 전화번호: 24040 519-931-5777
- 이메일: pfoster@robarts.ca
연구 장소
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Ontario
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London, Ontario, 캐나다, N6A 5B7
- Robarts Research Institute
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Men diagnosed with confirmed adenocarcinoma of the prostate
- No history of skin hypersensitivities or allergies.
- Normal liver functions as defined by alanine aminotransferase (ALT) (3-36 U/L) and aspirate aminotransferase (AST) levels (10-34 U/L)
- Normal kidney function by monitoring urea (2.5-8.0 ηmol/L) and creatine (70-120 μmol/L [for males]) concentrations.
- Normal complete blood count with differential
- Body Weight between 40 and 110 kg (relates to being able to fit in scanner)
- Body Mass Index < 30 (relates to being able to fit in scanner)
- Negative for (HIV, HTLV1&2, Hep A, B, C, syphilis) infection as determined by approved serological testing.
Exclusion Criteria:
- Contraindication to venipuncture and donation of 100-160 mL of blood
- Active infection (not limited to HIV, HTLV1&2, Hep A, B, C, syphilis)
- Participants are on active chemotherapy (not including castrate hormone therapy), radiation therapy or immunosuppressive therapy (i.e. steroid use, anti-transplant rejection drugs, depleting antibodies)
- Participants who are unable to have an MRI scan (e.g. history of head or eye injury involving metal fragments, implanted electrical device (such as a cardiac pacemaker), conductive implants or devices such as skin patches, body piercing or tattoos containing metallic inks, severe heart disease (including susceptibility to heart rhythm abnormalities), claustrophobia, etc.)
- Participants with known allergies to phenol red, β-lactams and β-lactam derivative
- Participants with known allergies to streptomycin sulfate and gentamicin sulfate
- Participants with unforeseen conditions that are deemed unsafe or inappropriate for the study (e.g. participants who are claustrophobic and cannot undergo an MRI) as per the discretion of the principal investigator.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위화되지 않음
- 중재 모델: 요인 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
---|---|
실험적: Prostate Cancer Patients
Up to 6 Male prostate cancer patients with metastatic, castration resistant prostate cancer will be enrolled. 19F Cell Sense-labeled PBMC (3 million cells) will be injected intradermally into the upper thigh of each participant above the inguinal lymph node. MRI will be used to image the administration site. |
Peripheral blood mononuclear cells (PBMC) will be isolated from patient whole blood samples and labeled in a GMP facility with GMP grade 19F Cell Sense imaging agent. These cells will be re-administered to the patient prior to imaging.
Participants will undergo Magnetic Resonance Imaging (MRI) at 1 hour and 24 hours following PBMC administration
|
실험적: Healthy Volunteers
Up to 6 male or female healthy volunteers will be enrolled. 19F Cell Sense-labeled PBMC (3 million cells) will be injected intradermally into the upper thigh of each participant above the inguinal lymph node. MRI will be used to image the administration site. |
Peripheral blood mononuclear cells (PBMC) will be isolated from patient whole blood samples and labeled in a GMP facility with GMP grade 19F Cell Sense imaging agent. These cells will be re-administered to the patient prior to imaging.
Participants will undergo Magnetic Resonance Imaging (MRI) at 1 hour and 24 hours following PBMC administration
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
---|---|
Number of participants with treatment-related adverse effects as assessed by CTCAE v4.0
기간: 12 months
|
12 months
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Number of patients with detectable 19F MRI signal at the site of injection
기간: 1hr post injection
|
This process will involve testing if the number of PBMC at the site of injection can be visualized and quantified following injection. Signal produced by labeled cells is linearly related to the number of cells. In vivo quantification has been demonstrated in animal modes, but not in a clinical setting to date. If necessary, specific imaging parameters will be adjusted to optimize for clinical anatomical and 19F cell tracking imaging. |
1hr post injection
|
Number of patients with detectable 19F MRI signal at local lymph nodes
기간: 24 hours post injection
|
PBMC are required to migrate to the lymph node for optimum therapeutic effect.
Here the investigators will determine if 19F-MRI contains the necessary imaging sensitivity to detect migration.
|
24 hours post injection
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Gregory A Dekaban, PhD, Robarts Research Institte - Western Universtiy
- 수석 연구원: Paula J Foster, PhD, Robarts Research Institte - Western Universtiy
- 수석 연구원: Sowmya Vuswanathan, PhD, University Health Network - University of Toronto
- 연구 의자: Joseph Chin, MD, London Health Research Institute - Western University
- 연구 의자: Michael Rieder, MD PhD, Robarts Research Institte - Western University
- 연구 의자: Gary Brahm, MD, London Health Research Institute
- 연구 의자: Doreen Matsui, MD, Western University
- 연구 의자: George Dresser, MD, Western University
연구 기록 날짜
연구 주요 날짜
연구 시작 (예상)
기본 완료 (예상)
연구 완료 (예상)
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
기타 연구 ID 번호
- CS-PBMC-2015-001
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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