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Immunotherapy for Third Line Metastatic Colorectal Cancer (STIMVAX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04444622
Recruitment Status : Not yet recruiting
First Posted : June 23, 2020
Last Update Posted : January 20, 2021
Mirror Biologics, Inc.
Information provided by (Responsible Party):
Immunovative Therapies, Ltd.

Tracking Information
First Submitted Date  ICMJE June 19, 2020
First Posted Date  ICMJE June 23, 2020
Last Update Posted Date January 20, 2021
Estimated Study Start Date  ICMJE March 6, 2021
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • Overall Survival [ Time Frame: date of death from any cause, whichever came first, assessed up to 12 months from accrual ]
    measurement of the survival on experimental treatment
  • Incidents of Adverse Events (AE) [ Time Frame: day 0 to 1 year ]
    to evaluate safety and tolerability
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Immunotherapy for Third Line Metastatic Colorectal Cancer
Official Title  ICMJE Phase IIB Open-Label Study to Assess the Safety and Efficacy of STIMVAX® as Third-line Therapy for Metastatic Colorectal Cancer
Brief Summary 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.
Detailed Description

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".

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Colorectal Cancer
Intervention  ICMJE Biological: AlloStim
Living bioengineered, non-genetically manipulated, activated Th1-like immune cells differentiated and expanded from precursor cells purified from blood of healthy unrelated donors
Other Name: StimVax
Study Arms  ICMJE Experimental: AlloStim

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: Biological: AlloStim
Publications * 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. Epub 2007 Dec 3.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 22, 2020)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult males and female subjects aged 18-80 years at screening visit
  2. Pathologically confirmed diagnosis of colorectal adenocarcinoma
  3. Presenting with metastatic disease:

    • Primary can be intact or previously resected
    • Preferably with metastasis to the liver or other location for safe percutaneous biopsy
  4. Previous treatment failure of two previous lines of active systemic chemotherapy:

    • Previous chemotherapy must have included an oxaliplatin-containing (e.g. FOLFOX) and an irinotecan-containing (e.g. FOLFIRI) regimen
    • With or without bevacizumab
    • Administered in adjuvant setting or for treatment of metastatic disease
    • If KRAS wild type, must have at least one prior anti-EGFR therapy
    • Treatment failure can be due to disease progression or toxicity
    • Disease progression on second line therapy must be documented radiologically and must have occurred during or within 30 days following the last administration of treatment for metastatic disease
  5. ECOG performance score: 0-1
  6. Adequate hematological function:

    • Absolute granulocyte count ≥ 1,200/mm3
    • Platelet count ≥ 100,000/mm3
    • PT/INR ≤ 1.5 or correctable to <1.5 at time of interventional procedures
    • Hemoglobin ≥ 9 g/dL (may be corrected by transfusion)
  7. Adequate Organ Function:

    • Creatinine ≤ 1.5 mg/dL
    • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
    • Alkaline phosphatase ≤ 2.5 times ULN *
    • Aspartate aminotransferase (AST) or (SGOT) ≤ 2.5 times ULN *
    • Alanine aminotransferase (ALT) or (SGPT) ≤ 2.5 times ULN * *or ≤5x ULN if liver involvement
  8. EKG without clinically relevant abnormalities
  9. Female subjects: Not pregnant or lactating
  10. Patients with child bearing potential must agree to use adequate contraception
  11. Study specific informed consent in the native language of the subject.

Exclusion Criteria:

  1. high frequency microsatellite instability (MSI-H)
  2. Bowel obstruction or high risk for obstruction if tumors become inflamed
  3. Moderate or severe ascites requiring medical intervention
  4. Clinical evidence or radiological evidence of brain metastasis or leptomeningeal involvement
  5. Peritoneal carcinomatosis
  6. Symptomatic asthma or COPD
  7. Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment; or, oxygen saturation <92% on room air
  8. Bevacizumab (Avastin®) treatment within 6 weeks of baseline scheduled biopsy procedure
  9. Any of the following mood disorders: active major depressive episode, history of suicidal attempt or ideation
  10. Prior allogeneic bone marrow/stem cell or solid organ transplant
  11. Chronic use (> 2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to > 5 mg/day of prednisone) within 30 days of the first day of study drug treatment

    • Topical corticosteroids are permitted
  12. Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis).

    • Well controlled Type I diabetes allowed
  13. Prior experimental therapy
  14. History of blood transfusion reactions
  15. Progressive viral or bacterial infection

    • All infections must be resolved and the subject must remain afebrile for seven days without antibiotics prior to being placed on study
  16. Cardiac disease of symptomatic nature
  17. History of HIV positivity or AIDS
  18. Concurrent medication known to interfere with platelet function or coagulation (e.g., aspirin, ibuprofen, clopidogrel, or warfarin) unless such medications can be discontinued for an appropriate time period based on the drug half-life and known activity (e.g., aspirin for 7 days) prior to biopsy procedures
  19. History of severe hypersensitivity to monoclonal antibody drugs
  20. Psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation.
  21. Subjects that lack ability to provide consent for themselves.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kim Demonte 732-630-9059
Contact: Thu Bui, MHA 619-227-4872
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04444622
Other Study ID Numbers  ICMJE ITL-032-MCRC3-STIM
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Immunovative Therapies, Ltd.
Study Sponsor  ICMJE Immunovative Therapies, Ltd.
Collaborators  ICMJE Mirror Biologics, Inc.
Investigators  ICMJE Not Provided
PRS Account Immunovative Therapies, Ltd.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP