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

Sponsor

Pawel Kalinski (Other)

Overall Status

Completed

CT.gov ID

NCT01671592

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

14.9

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms Colorectal Cancer Colorectal Carcinoma Colorectal Tumors Neoplasms, Colorectal	Biological: DC Vaccine	Phase 1

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Day 1 MRI with low dose vaccine 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 Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.
Experimental: Day 3 MRI with low dose vaccine 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 Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.
Experimental: Day 1 MRI with high dose vaccine 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 Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.
Experimental: Day 3 MRI with high dose vaccine 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 Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.

Outcome Measures

Primary Outcome Measures

Adverse events from the labeled DC vaccine [1 year]
Ability to track the labeled DC vaccine by MRI [1 year]

Secondary Outcome Measures

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. [1 year]
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.
May assess the disease-free survival and overall survival [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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