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

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

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

Study Overview

• Status: Completed
• Conditions: Colorectal Neoplasms; Colorectal Cancer; Colorectal Tumors; Colorectal Carcinoma; Neoplasms, Colorectal
• Intervention / Treatment: Biological: DC Vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Pawel Kalinski
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David L. Bartlett, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: August 20, 2012
• First Submitted That Met QC Criteria: August 22, 2012
• First Posted (Estimate): August 23, 2012

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 25, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Cancer; carcinoma; vaccine; colorectal; neoplasms; tumor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms; Colorectal Neoplasms
• Other Study ID Numbers: 10-052; R01CA134633 (U.S. NIH Grant/Contract)