<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01671592</url>
  </required_header>
  <id_info>
    <org_study_id>10-052</org_study_id>
    <secondary_id>R01CA134633</secondary_id>
    <nct_id>NCT01671592</nct_id>
  </id_info>
  <brief_title>Safety of Labeled Dendritic Cell (DC) Vaccines and Feasibility of Tracking by Magnetic Resonance Imaging (MRI)</brief_title>
  <official_title>Safety and Feasibility Evaluation of the MRI-based Tracking of Alpha-type-1 Dendritic Cell Vaccines in Patients With Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pawel Kalinski</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety and feasibility MRI tracking of a vaccine produced from a&#xD;
      persons cancer cells injected intradermally once a day for 3 consecutive days. One of the&#xD;
      daily doses will contain a chemical that can be detected by an MRI. That will be either the&#xD;
      1st or 3rd day of the 3 day course. On that day MRI scans will be performed 6 and 24 hours&#xD;
      after the injection on that day. Patients may be able to receive booster doses every 1-2&#xD;
      months&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STUDY EVALUATIONS&#xD;
&#xD;
        -  Pre-Vaccination&#xD;
&#xD;
             -  Complete physical examination (with ECOG performance status (PS), medical history,&#xD;
                weight, height, and BSA); the exact size and location of all tumor lesions will be&#xD;
                noted in the flow sheet, documented in the text note, and by photographic and/or&#xD;
                radiologic means&#xD;
&#xD;
             -  CEA levels in the blood (as a tumor marker)&#xD;
&#xD;
             -  Women of childbearing potential will have a serum beta-HCG pregnancy test&#xD;
&#xD;
             -  Anti-HIV, HbsAg and Anti-HCV&#xD;
&#xD;
             -  CBC, platelet, differential&#xD;
&#xD;
             -  Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium,&#xD;
                potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST,&#xD;
                ALT, total bilirubin&#xD;
&#xD;
             -  PT/PTT testing&#xD;
&#xD;
             -  Electrocardiogram (EKG), if indicated&#xD;
&#xD;
             -  Radiologic imaging to evaluate the status of disease may be performed as a part of&#xD;
                routine care.&#xD;
&#xD;
             -  Leukapheresis&#xD;
&#xD;
             -  Dendritic cell vaccine preparation&#xD;
&#xD;
        -  Procedures during priming vaccination (Days 1 to 3)&#xD;
&#xD;
             -  Complete physical examination (with PS and weight)&#xD;
&#xD;
             -  19F/1H MRI scanning on day of vaccination, 6 hrs (±1 hour) and 24 hrs (±4 hour)&#xD;
                post-injection.&#xD;
&#xD;
             -  Blood for in vitro assays, before first i.d. administration on day 1 (baseline) and&#xD;
                after the last i.d. administration on day 3&#xD;
&#xD;
             -  DTH tests: administration on day 1 and readout on day 3&#xD;
&#xD;
             -  Biopsy of the DTH site can be performed in any subject who consented to such&#xD;
                biopsy, at the discretion of the investigator/sub-investigator (Day 3 only, based&#xD;
                on readout)&#xD;
&#xD;
        -  Procedures on Day 15&#xD;
&#xD;
             -  Complete physical examination (with ECOG PS and weight)&#xD;
&#xD;
             -  CBC, platelet, differential&#xD;
&#xD;
             -  Blood for in vitro assays&#xD;
&#xD;
        -  Procedures during booster courses (Days 36 to 38, 64 to 66, and 91 to 93)&#xD;
&#xD;
             -  Complete physical examination (with PS and weight) on the 1st day of each 3 day&#xD;
                course (Days 36, 64, and 91)&#xD;
&#xD;
             -  CBC, platelet, differential on the 1st day of each 3 day course (Days 36, 64, and&#xD;
                91)&#xD;
&#xD;
             -  Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium,&#xD;
                potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST,&#xD;
                ALT, total bilirubin on the 1st day of each 3 day course (Days 36, 64, and 91)&#xD;
&#xD;
             -  DTH tests: administration on 1st day and readout on 3rd day during 2nd and 3rd&#xD;
                booster courses (Administration days 64 and 91, readout days 66 and 93)&#xD;
&#xD;
             -  Biopsy of the DTH site can be performed in any subject who consented to such&#xD;
                biopsy, at the discretion of the investigator/sub-investigator (3rd day of 3 day&#xD;
                course, based on readout of DTH test)&#xD;
&#xD;
             -  Blood for in vitro assays (1st and 3rd day of each 3 day course)&#xD;
&#xD;
        -  Procedures on Day 105&#xD;
&#xD;
             -  Complete physical examination (with ECOG PS and weight)&#xD;
&#xD;
             -  CEA levels in the blood (as a tumor marker)&#xD;
&#xD;
             -  CBC, platelet, differential&#xD;
&#xD;
             -  Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium,&#xD;
                potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST,&#xD;
                ALT, total bilirubin&#xD;
&#xD;
             -  Radiologic imaging to evaluate the status of disease may be performed as a part of&#xD;
                routine care&#xD;
&#xD;
             -  Photography&#xD;
&#xD;
        -  Long term follow-up The subjects with lack of disease progression at 6 months after the&#xD;
           last vaccination will be monitored for the disease free survival and overall survival.&#xD;
           Subjects may be contacted every 3 months within the first three years after study&#xD;
           intervention, every six months until year 5, and annually afterwards. In lieu of direct&#xD;
           contact a medical record review may be performed to obtain the data for these time&#xD;
           points for disease progression and/or survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">April 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events from the labeled DC vaccine</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ability to track the labeled DC vaccine by MRI</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>1 year</time_frame>
    <description>Effectiveness of DC accumulation may be correlated with their effectiveness in inducing immune responses as measured by:&#xD;
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.&#xD;
Peripheral blood CD8+ and CD4+ T cell responses against autologous tumor cells, using IFNγ-ELISPOT readout.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>May assess the disease-free survival and overall survival</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Colorectal Neoplasms</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Colorectal Carcinoma</condition>
  <condition>Colorectal Tumors</condition>
  <condition>Neoplasms, Colorectal</condition>
  <arm_group>
    <arm_group_label>Day 1 MRI with low dose vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Day 3 MRI with low dose vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Day 1 MRI with high dose vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Day 3 MRI with high dose vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DC Vaccine</intervention_name>
    <description>Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.</description>
    <arm_group_label>Day 1 MRI with high dose vaccine</arm_group_label>
    <arm_group_label>Day 1 MRI with low dose vaccine</arm_group_label>
    <arm_group_label>Day 3 MRI with high dose vaccine</arm_group_label>
    <arm_group_label>Day 3 MRI with low dose vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have adequate tumor tissue from surgery, performed as part of their&#xD;
             conventional care.&#xD;
&#xD;
          -  No chemotherapy, radiotherapy, major surgery, or biologic therapy for their malignancy&#xD;
             in the 2 weeks prior to vaccine administration and they must have recovered from all&#xD;
             side effects.&#xD;
&#xD;
          -  An ECOG performance status of 0, 1, or 2.&#xD;
&#xD;
          -  Age equal to 18 years or older.&#xD;
&#xD;
          -  Blood tests:&#xD;
&#xD;
               -  Platelet counts greater than 80,000 (platelet count, hematocrit, and WBC will be&#xD;
                  re-evaluated within 2 weeks prior to leukapheresis)&#xD;
&#xD;
               -  Hematocrit &gt; 27.0&#xD;
&#xD;
               -  White blood count &gt; 2000/µL&#xD;
&#xD;
               -  Creatinine less than or equal to 2 X ULN&#xD;
&#xD;
          -  Aware of the neoplastic nature of his/her illness, the experimental nature of the&#xD;
             study intervention, alternative treatments, potential benefits and risks, and willing&#xD;
             to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects currently treated with systemic immunosuppressive agents, including steroids,&#xD;
             are ineligible until 2 weeks after removal from immunosuppressive treatment. Subjects&#xD;
             on maintenance steroids because of adrenal insufficiency are eligible.&#xD;
&#xD;
          -  Subjects with total bilirubin greater than 2 X ULN.&#xD;
&#xD;
          -  Subjects with uncontrolled pain.&#xD;
&#xD;
          -  Subjects with active autoimmune disease, positive serology for HIV, HBV, or HCV.&#xD;
             (Hypothyroidism is allowed.)&#xD;
&#xD;
          -  Subjects who are allergic to or develop an allergy to heparin.&#xD;
&#xD;
          -  Subjects who are pregnant.&#xD;
&#xD;
          -  Subjects who have sensitivity to drugs that provide local anesthesia.&#xD;
&#xD;
          -  Subjects who have medical contraindications for MRI. Such contraindications include:&#xD;
&#xD;
               -  Electrical implants such as cardiac pacemakers or perfusion pumps&#xD;
&#xD;
               -  Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses,&#xD;
                  artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos&#xD;
                  near the eye or steel implants&#xD;
&#xD;
               -  Ferromagnetic objects such as jewelry or metal clips in clothing&#xD;
&#xD;
               -  Pre-existing medical conditions, including claustrophobic reactions, the&#xD;
                  likelihood of developing a seizure or any greater than normal potential for&#xD;
                  cardiac arrest&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David L. Bartlett, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 20, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <last_update_submitted>September 25, 2017</last_update_submitted>
  <last_update_submitted_qc>September 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Pawel Kalinski</investigator_full_name>
    <investigator_title>Professor of Surgery</investigator_title>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>colorectal</keyword>
  <keyword>tumor</keyword>
  <keyword>neoplasms</keyword>
  <keyword>carcinoma</keyword>
  <keyword>vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01671592
org study id: 10-052
secondary id: R01CA134633
nct id: NCT01671592
lead sponsor: 
collaborator: 
has dmc: Yes
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 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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events from the labeled DC vaccine
time frame: 1 year
measure: Ability to track the labeled DC vaccine by MRI
time frame: 1 year
measure: 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.
time frame: 1 year
description: 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.
measure: May assess the disease-free survival and overall survival
time frame: 5 years
arm group label: Day 1 MRI with low dose vaccine
arm group type: Experimental
description: 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.
arm group label: Day 3 MRI with low dose vaccine
arm group type: Experimental
description: 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.
arm group label: Day 1 MRI with high dose vaccine
arm group type: Experimental
description: 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.
arm group label: Day 3 MRI with high dose vaccine
arm group type: Experimental
description: 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.
intervention type: Biological
intervention name: DC Vaccine
description: Alpha-type-1-polarized dendritic cells (αDC1) pulsed with apoptotic autologous tumor.
arm group label: Day 1 MRI with high dose vaccine
arm group label: Day 1 MRI with low dose vaccine
arm group label: Day 3 MRI with high dose vaccine
arm group label: Day 3 MRI with low dose vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David L. Bartlett, MD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Pawel Kalinski
investigator title: Professor of Surgery
mesh term: Neoplasms
mesh term: Colorectal Neoplasms