<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/NCT04444622</url>
  </required_header>
  <id_info>
    <org_study_id>ITL-032-MCRC3-STIM</org_study_id>
    <nct_id>NCT04444622</nct_id>
  </id_info>
  <brief_title>Immunotherapy for Third Line Metastatic Colorectal Cancer</brief_title>
  <acronym>STIMVAX</acronym>
  <official_title>Phase IIB Open-Label Study to Assess the Safety and Efficacy of STIMVAX® as Third-line Therapy for Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Immunovative Therapies, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mirror Biologics, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Immunovative Therapies, Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase IIB multi-site, open label study of a next generation immunotherapy for&#xD;
      third-line MSI-S metastatic colorectal cancer using an &quot;off-the-shelf&quot;, non-genetically&#xD;
      manipulated living immune cell product (AlloStim) derived from the blood of healthy donors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase IIB open label immunotherapy protocol called &quot;StimVax&quot;. The protocol design&#xD;
      is based upon information obtained from a previous Phase IIA dose level and dose frequency&#xD;
      ranging study. The population targeted is MSI-S metastatic colorectal cancer previously&#xD;
      treated with two lines of chemotherapy regimens, one containing oxaliplatin and the other&#xD;
      containing irinotecan. This population is not considered to be responsive to immunotherapy.&#xD;
&#xD;
      The study drug is called &quot;AlloStim&quot;. AlloStim is an &quot;off-the-shelf&quot;,&#xD;
      non-genetically-manipulated, living immune cell immunotherapy. AlloStim is derived from&#xD;
      precursors purified from the blood of healthy donors and grown and differentiated in&#xD;
      specialized bioreactors in the laboratory. Because the donors are intentionally mis-matched&#xD;
      to the host, AlloStim is completely eliminated by the host in a non-toxic rejection response&#xD;
      within 24h of administration.&#xD;
&#xD;
      Unlike autologous immune cell therapies, like CAR-T cells or TIL cells, AlloStim is&#xD;
      allogeneic and is not intended to directly kill tumors. Rather, the novel AlloStim mechanism&#xD;
      is designed to modify and train the host immune system to kill tumors and prevent tumor&#xD;
      growth and spread. Uniquely, the AlloStim mechanism is also designed to increase Th1/Th2&#xD;
      balance, activate innate effector cells (such as NK and NKT), counter-regulate the immune&#xD;
      suppressive and immune evasion mechanisms that tumors use to evade immune elimination both&#xD;
      systemically and in the tumor microenvironment.&#xD;
&#xD;
      The AlloStim mechanism creates self-amplifying waves of temporal and spatial immune effects&#xD;
      that can lead to an initial non-specific cellular innate NK cell immune response followed by&#xD;
      a tumor-specific killer T-cell immune response specific for the host tumor through a&#xD;
      combination of immune processes called &quot;allo-priming&quot; and &quot;in-situ vaccination&quot;.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 12, 2021</start_date>
  <completion_date type="Anticipated">April 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>date of death from any cause, whichever came first, assessed up to 12 months from accrual</time_frame>
    <description>measurement of the survival on experimental treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidents of Adverse Events (AE)</measure>
    <time_frame>day 0 to 1 year</time_frame>
    <description>to evaluate safety and tolerability</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>AlloStim</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AlloStim is administered in three cycles:&#xD;
Cycle 1 Day 0: 0.5ml ID AlloStim® Day 7: 0.5ml ID AlloStim® Day 14: 0.5ml ID AlloStim® Day 21: 0.5ml ID AlloStim® Day 28: 0.5ml ID AlloStim®&#xD;
Cycle 2 Day 42: 0.5ml ID AlloStim® Day 49: 0.5ml ID AlloStim® Day 56: 0.5ml ID AlloStim® Day 63: 0.5ml ID AlloStim® Day 70: 0.5ml ID AlloStim® + 3ml IV AlloStim®&#xD;
Cycle 3 Day 84: 0.5ml ID AlloStim® Day 91: 0.5ml ID AlloStim® Day 98: 0.5ml ID AlloStim® Day 105: 0.5ml ID AlloStim® Day 112: 0.5ml ID AlloStim® + 3ml IV AlloStim®</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AlloStim</intervention_name>
    <description>Living bioengineered, non-genetically manipulated, activated Th1-like immune cells differentiated and expanded from precursor cells purified from blood of healthy unrelated donors</description>
    <arm_group_label>AlloStim</arm_group_label>
    <other_name>StimVax</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult males and female subjects aged 18-80 years at screening visit&#xD;
&#xD;
          2. Pathologically confirmed diagnosis of colorectal adenocarcinoma&#xD;
&#xD;
          3. Presenting with metastatic disease:&#xD;
&#xD;
          4. Previous treatment failure of two previous lines of active systemic chemotherapy:&#xD;
&#xD;
               -  Previous chemotherapy must have included an oxaliplatin-containing (e.g. FOLFOX)&#xD;
                  and an irinotecan-containing (e.g. FOLFIRI) regimen&#xD;
&#xD;
               -  With or without bevacizumab&#xD;
&#xD;
               -  Administered in adjuvant setting or for treatment of metastatic disease&#xD;
&#xD;
               -  If KRAS wild type, must have at least one prior anti-EGFR therapy&#xD;
&#xD;
               -  Treatment failure can be due to disease progression or toxicity&#xD;
&#xD;
               -  Disease progression on second line therapy must be documented radiologically and&#xD;
                  must have occurred during or within 30 days following the last administration of&#xD;
                  treatment for metastatic disease&#xD;
&#xD;
          5. ECOG performance score: 0-1&#xD;
&#xD;
          6. Adequate hematological function:&#xD;
&#xD;
               -  Absolute granulocyte count ≥ 1,200/mm3&#xD;
&#xD;
               -  Platelet count ≥ 100,000/mm3&#xD;
&#xD;
               -  PT/INR ≤ 1.5 or correctable to &lt;1.5 at time of interventional procedures&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL (may be corrected by transfusion)&#xD;
&#xD;
          7. Adequate Organ Function:&#xD;
&#xD;
               -  Creatinine ≤ 1.5 mg/dL&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN)&#xD;
&#xD;
               -  Alkaline phosphatase ≤ 2.5 times ULN *&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) or (SGOT) ≤ 2.5 times ULN *&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) or (SGPT) ≤ 2.5 times ULN * *or ≤5x ULN if liver&#xD;
                  involvement&#xD;
&#xD;
          8. EKG without clinically relevant abnormalities&#xD;
&#xD;
          9. Female subjects: Not pregnant or lactating&#xD;
&#xD;
         10. Patients with child bearing potential must agree to use adequate contraception&#xD;
&#xD;
         11. Study specific informed consent in the native language of the subject.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. high frequency microsatellite instability (MSI-H)&#xD;
&#xD;
          2. Bowel obstruction or high risk for obstruction if tumors become inflamed&#xD;
&#xD;
          3. Moderate or severe ascites requiring medical intervention&#xD;
&#xD;
          4. Clinical evidence or radiological evidence of brain metastasis or leptomeningeal&#xD;
             involvement&#xD;
&#xD;
          5. Peritoneal carcinomatosis&#xD;
&#xD;
          6. Symptomatic asthma or COPD&#xD;
&#xD;
          7. Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in&#xD;
             pulmonary dysfunction requiring active treatment; or, oxygen saturation &lt;92% on room&#xD;
             air&#xD;
&#xD;
          8. Bevacizumab (Avastin®) treatment within 6 weeks of baseline scheduled biopsy procedure&#xD;
&#xD;
          9. Any of the following mood disorders: active major depressive episode, history of&#xD;
             suicidal attempt or ideation&#xD;
&#xD;
         10. Prior allogeneic bone marrow/stem cell or solid organ transplant&#xD;
&#xD;
         11. Chronic use (&gt; 2 weeks) of greater than physiologic doses of a corticosteroid agent&#xD;
             (dose equivalent to &gt; 5 mg/day of prednisone) within 30 days of the first day of study&#xD;
             drug treatment&#xD;
&#xD;
               -  Topical corticosteroids are permitted&#xD;
&#xD;
         12. Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple&#xD;
             sclerosis, autoimmune thyroid disease, uveitis).&#xD;
&#xD;
               -  Well controlled Type I diabetes allowed&#xD;
&#xD;
         13. Prior experimental therapy&#xD;
&#xD;
         14. History of blood transfusion reactions&#xD;
&#xD;
         15. Progressive viral or bacterial infection&#xD;
&#xD;
               -  All infections must be resolved and the subject must remain afebrile for seven&#xD;
                  days without antibiotics prior to being placed on study&#xD;
&#xD;
         16. Cardiac disease of symptomatic nature&#xD;
&#xD;
         17. History of HIV positivity or AIDS&#xD;
&#xD;
         18. Concurrent medication known to interfere with platelet function or coagulation (e.g.,&#xD;
             aspirin, ibuprofen, clopidogrel, or warfarin) unless such medications can be&#xD;
             discontinued for an appropriate time period based on the drug half-life and known&#xD;
             activity (e.g., aspirin for 7 days) prior to biopsy procedures&#xD;
&#xD;
         19. History of severe hypersensitivity to monoclonal antibody drugs&#xD;
&#xD;
         20. Psychiatric or addictive disorders or other condition that, in the opinion of the&#xD;
             investigator, would preclude study participation.&#xD;
&#xD;
         21. Subjects that lack ability to provide consent for themselves.&#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_contact>
    <last_name>Kim Demonte</last_name>
    <phone>732-630-9059</phone>
    <email>axellaresearch@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Thu Bui, MHA</last_name>
    <phone>619-227-4872</phone>
    <email>thu@immunovative.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Mt. Sinai Comprehensive Cancer Center</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luz Smith</last_name>
      <phone>305-674-2625</phone>
      <email>Luz.Smith@msmc.com</email>
    </contact>
    <investigator>
      <last_name>Mike Cusnir, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Oleg Gligich, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gerard Chaaya, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jacqueline Barrientos, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ragisha Gopalakrishnan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Aron Simkins, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michael Schwartz, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Prachi Shah</last_name>
      <phone>313-576-9382</phone>
      <email>shahp@karmanos.org</email>
    </contact>
    <contact_backup>
      <last_name>Paige Buzenski</last_name>
      <phone>313-576-9380</phone>
      <email>buzenskp@karmanos.org</email>
    </contact_backup>
    <investigator>
      <last_name>Mohammed Al Hallak, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Summit Health</name>
      <address>
        <city>Florham Park</city>
        <state>New Jersey</state>
        <zip>07932</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michelle Mackenzie, RN</last_name>
      <phone>973-436-1752</phone>
      <email>mmackenzie@summithealth.com</email>
    </contact>
    <investigator>
      <last_name>David Gallinson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hirschfield Oncology Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10469</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Karla Witkowski</last_name>
      <phone>718-732-4050</phone>
      <email>karla@honcology.com</email>
    </contact>
    <investigator>
      <last_name>Azriel Hirschfeld, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70(6):1186-92. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.</citation>
    <PMID>18054441</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>immunotherapy</keyword>
  <keyword>cancer vaccine</keyword>
  <keyword>colorectal cancer</keyword>
  <keyword>AlloStim</keyword>
  <keyword>MSI-S</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT04444622
org study id: ITL-032-MCRC3-STIM
nct id: NCT04444622
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase IIB multi-site, open label study of a next generation immunotherapy for
      third-line MSI-S metastatic colorectal cancer using an "off-the-shelf", non-genetically
      manipulated living immune cell product (AlloStim) derived from the blood of healthy donors.
This is a Phase IIB open label immunotherapy protocol called "StimVax". The protocol design
      is based upon information obtained from a previous Phase IIA dose level and dose frequency
      ranging study. The population targeted is MSI-S metastatic colorectal cancer previously
      treated with two lines of chemotherapy regimens, one containing oxaliplatin and the other
      containing irinotecan. This population is not considered to be responsive to immunotherapy.

      The study drug is called "AlloStim". AlloStim is an "off-the-shelf",
      non-genetically-manipulated, living immune cell immunotherapy. AlloStim is derived from
      precursors purified from the blood of healthy donors and grown and differentiated in
      specialized bioreactors in the laboratory. Because the donors are intentionally mis-matched
      to the host, AlloStim is completely eliminated by the host in a non-toxic rejection response
      within 24h of administration.

      Unlike autologous immune cell therapies, like CAR-T cells or TIL cells, AlloStim is
      allogeneic and is not intended to directly kill tumors. Rather, the novel AlloStim mechanism
      is designed to modify and train the host immune system to kill tumors and prevent tumor
      growth and spread. Uniquely, the AlloStim mechanism is also designed to increase Th1/Th2
      balance, activate innate effector cells (such as NK and NKT), counter-regulate the immune
      suppressive and immune evasion mechanisms that tumors use to evade immune elimination both
      systemically and in the tumor microenvironment.

      The AlloStim mechanism creates self-amplifying waves of temporal and spatial immune effects
      that can lead to an initial non-specific cellular innate NK cell immune response followed by
      a tumor-specific killer T-cell immune response specific for the host tumor through a
      combination of immune processes called "allo-priming" and "in-situ vaccination".
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival
time frame: date of death from any cause, whichever came first, assessed up to 12 months from accrual
description: measurement of the survival on experimental treatment
measure: Incidents of Adverse Events (AE)
time frame: day 0 to 1 year
description: to evaluate safety and tolerability
arm group label: AlloStim
arm group type: Experimental
description: AlloStim is administered in three cycles:
Cycle 1 Day 0: 0.5ml ID AlloStim® Day 7: 0.5ml ID AlloStim® Day 14: 0.5ml ID AlloStim® Day 21: 0.5ml ID AlloStim® Day 28: 0.5ml ID AlloStim®
Cycle 2 Day 42: 0.5ml ID AlloStim® Day 49: 0.5ml ID AlloStim® Day 56: 0.5ml ID AlloStim® Day 63: 0.5ml ID AlloStim® Day 70: 0.5ml ID AlloStim® + 3ml IV AlloStim®
Cycle 3 Day 84: 0.5ml ID AlloStim® Day 91: 0.5ml ID AlloStim® Day 98: 0.5ml ID AlloStim® Day 105: 0.5ml ID AlloStim® Day 112: 0.5ml ID AlloStim® + 3ml IV AlloStim®
intervention type: Biological
intervention name: AlloStim
description: Living bioengineered, non-genetically manipulated, activated Th1-like immune cells differentiated and expanded from precursor cells purified from blood of healthy unrelated donors
arm group label: AlloStim
other name: StimVax
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kim Demonte
phone: 732-630-9059
email: axellaresearch@gmail.com
last name: Thu Bui, MHA
phone: 619-227-4872
email: thu@immunovative.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
citation: Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70(6):1186-92. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.
PMID: 18054441
responsible party type: Sponsor
mesh term: Colorectal Neoplasms