Safety of Labeled Dendritic Cell (DC) Vaccines and Feasibility of Tracking by Magnetic Resonance Imaging (MRI)

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the safety and feasibility MRI tracking of a vaccine produced from a persons cancer cells injected intradermally once a day for 3 consecutive days. One of the daily doses will contain a chemical that can be detected by an MRI. That will be either the 1st or 3rd day of the 3 day course. On that day MRI scans will be performed 6 and 24 hours after the injection on that day. Patients may be able to receive booster doses every 1-2 months

Detailed Description
-----------------
STUDY EVALUATIONS Pre-Vaccination Complete physical examination (with ECOG performance status (PS), medical history, weight, height, and BSA); the exact size and location of all tumor lesions will be noted in the flow sheet, documented in the text note, and by photographic and/or radiologic means CEA levels in the blood (as a tumor marker) Women of childbearing potential will have a serum beta-HCG pregnancy test Anti-HIV, HbsAg and Anti-HCV CBC, platelet, differential Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium, potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin PT/PTT testing Electrocardiogram (EKG), if indicated Radiologic imaging to evaluate the status of disease may be performed as a part of routine care. Leukapheresis Dendritic cell vaccine preparation Procedures during priming vaccination (Days 1 to 3) Complete physical examination (with PS and weight) 19F/1H MRI scanning on day of vaccination, 6 hrs (±1 hour) and 24 hrs (±4 hour) post-injection. Blood for in vitro assays, before first i.d. administration on day 1 (baseline) and after the last i.d. administration on day 3 DTH tests: administration on day 1 and readout on day 3 Biopsy of the DTH site can be performed in any subject who consented to such biopsy, at the discretion of the investigator/sub-investigator (Day 3 only, based on readout) Procedures on Day 15 Complete physical examination (with ECOG PS and weight) CBC, platelet, differential Blood for in vitro assays Procedures during booster courses (Days 36 to 38, 64 to 66, and 91 to 93) Complete physical examination (with PS and weight) on the 1st day of each 3 day course (Days 36, 64, and 91) CBC, platelet, differential on the 1st day of each 3 day course (Days 36, 64, and 91) Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium, potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin on the 1st day of each 3 day course (Days 36, 64, and 91) DTH tests: administration on 1st day and readout on 3rd day during 2nd and 3rd booster courses (Administration days 64 and 91, readout days 66 and 93) Biopsy of the DTH site can be performed in any subject who consented to such biopsy, at the discretion of the investigator/sub-investigator (3rd day of 3 day course, based on readout of DTH test) Blood for in vitro assays (1st and 3rd day of each 3 day course) Procedures on Day 105 Complete physical examination (with ECOG PS and weight) CEA levels in the blood (as a tumor marker) CBC, platelet, differential Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium, potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin Radiologic imaging to evaluate the status of disease may be performed as a part of routine care Photography Long term follow-up The subjects with lack of disease progression at 6 months after the last vaccination will be monitored for the disease free survival and overall survival. Subjects may be contacted every 3 months within the first three years after study intervention, every six months until year 5, and annually afterwards. In lieu of direct contact a medical record review may be performed to obtain the data for these time points for disease progression and/or survival.

Official Title
-----------------
Safety and Feasibility Evaluation of the MRI-based Tracking of Alpha-type-1 Dendritic Cell Vaccines in Patients With Colorectal Cancer

Conditions
-----------------
Colorectal Neoplasms, Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal

Intervention / Treatment
-----------------
* Biological: DC Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must have adequate tumor tissue from surgery, performed as part of their conventional care. No chemotherapy, radiotherapy, major surgery, or biologic therapy for their malignancy in the 2 weeks prior to vaccine administration and they must have recovered from all side effects. An ECOG performance status of 0, 1, or 2. Age equal to 18 years or older. Blood tests: Platelet counts greater than 80,000 (platelet count, hematocrit, and WBC will be re-evaluated within 2 weeks prior to leukapheresis) Hematocrit > 27.0 White blood count > 2000/µL Creatinine less than or equal to 2 X ULN Aware of the neoplastic nature of his/her illness, the experimental nature of the study intervention, alternative treatments, potential benefits and risks, and willing to sign a written informed consent document. Exclusion Criteria: Subjects currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 2 weeks after removal from immunosuppressive treatment. Subjects on maintenance steroids because of adrenal insufficiency are eligible. Subjects with total bilirubin greater than 2 X ULN. Subjects with uncontrolled pain. Subjects with active autoimmune disease, positive serology for HIV, HBV, or HCV. (Hypothyroidism is allowed.) Subjects who are allergic to or develop an allergy to heparin. Subjects who are pregnant. Subjects who have sensitivity to drugs that provide local anesthesia. Subjects who have medical contraindications for MRI. Such contraindications include: Electrical implants such as cardiac pacemakers or perfusion pumps Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye or steel implants Ferromagnetic objects such as jewelry or metal clips in clothing Pre-existing medical conditions, including claustrophobic reactions, the likelihood of developing a seizure or any greater than normal potential for cardiac arrest

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Day 1 MRI with low dose vaccine<br>DC vaccine at 3 x 10e6 per course which consists of 3 daily intradermal doses per course with the MRI on day 1 of the course. | Biological: DC Vaccine<br>* Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.<br>|
| Experimental: Day 3 MRI with low dose vaccine<br>DC vaccine at 3 x 10e6 per course which consists of 3 daily intradermal doses per course with the MRI on day 3 of the course. | Biological: DC Vaccine<br>* Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.<br>|
| Experimental: Day 1 MRI with high dose vaccine<br>DC vaccine at 3 x 10e7 per course which consists of 3 daily intradermal doses per course with the MRI on day 1 of the course. | Biological: DC Vaccine<br>* Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.<br>|
| Experimental: Day 3 MRI with high dose vaccine<br>DC vaccine at 3 x 10e7 per course which consists of 3 daily intradermal doses per course with the MRI on day 3 of the course. | Biological: DC Vaccine<br>* Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events from the labeled DC vaccine |  | 1 year | 
| Ability to track the labeled DC vaccine by MRI |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative analysis of the effectiveness of lymph node accumulation of DC vaccines injected to resting versus pre-activated nodes (DCs injected on day 1 versus day 3 of the three day-long vaccination cycle. | Effectiveness of DC accumulation may be correlated with their effectiveness in inducing immune responses as measured by: Increase in the magnitude in the DTH response to: A) autologous tumor lysates (primary endpoint of efficacy); B) KLH; and c) saline (control); all injected intradermally. Peripheral blood CD8+ and CD4+ T cell responses against autologous tumor cells, using IFNγ-ELISPOT readout. In any HLA-A2+ subjects on the protocol, we may evaluate peripheral blood CD8+ T cell responses against CRC-related peptide epitopes present, using IFN ELISPOT as readout. | 1 year | 
| May assess the disease-free survival and overall survival |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, colorectal, tumor, neoplasms, carcinoma, vaccine