human stem cell derived neurons

A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma

 

Summary

This phase I clinical trial will evaluate the safety and tolerability of a single tumor injection of Ad-RTS-hIL-12 given with veledimex, for patients with recurrent grade III or IV glioma.

Ad-RTS-hiL-12 is a genetically engineered, non-pathogenic form of an adenovirus that encodes the protein called interleukin 12 (IL-12). IL-12 is a protein that can improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells. It may also interfere with blood flow to the tumor.

When Ad-RTS-hiL-12 is administered to the tumor site, the modified adenovirus will infect the tumor cells and begin using host cell machinery to produce IL-12. Additional modifications ensure that Ad-RTS-hIL-12 will only initiate production of IL-12 protein if administered with veledimex, an oral drug.

In this phase I study, Ad-RTS-hIL-12 will be injected to the tumor site during surgical resection, along with oral veledimex. Eligible participants will stratified into two groups, depending on whether they are scheduled for tumor resection: 

  • Experimental Group 1 (tumor resection): Ad-RTS-hIL-12 (via free-hand injection) + veledimex
  • Experimental Group 2 (no tumor resection): Ad-RTS-hIL-12 (via stereotactic injection) + veledimex
Inclusion Criteria
  1. Male or female subjects ≥ 18 and ≤ 75 years of age
  2. Provision of written informed consent for tumor resection, stereotactic surgery, tumor biopsy, samples collection and treatment with investigational products prior to undergoing any study procedures
  3. Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue.
  4. Evidence of tumor recurrence/progression by MRI (RANO criteria) post standard initial therapy.
  5. Previous standard of care anti-tumor treatment including surgery and/or biopsy and chemoradiation. The washout periods from prior therapies are intended as follows:
    1. Nitrosoureas: 6 weeks
    2. Other cytotoxic agents: 4 weeks
    3. Anti-angiogenic agents including bevacizumab: 4 weeks
    4. Targeted agents including small-molecule tyrosine kinase inhibitors: 2 weeks
    5. Experimental immunotherapies: 3 months
    6. Vaccine based therapy: 3 months
  6.  Able to undergo standard MRI scans with contrast agent
  7. Karnofsky Performance Status ≥ 70
  8. Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
    1. Hemoglobin ≥ 9 g/L
    2. Lymphocytes > 500/ mm3
    3. Absolute Neutrophil Count ≥ 1500/ mm3
    4. Platelets ≥ 100,000/ mm3
    5. Serum creatinine ≤ 1.5 x ULN
    6. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤ 5 × ULN
    7. Total bilirubin < 1.5 x ULN
    8. International Normalized Ratio (INR) and activated Partial Thromboplastin Time [PTT] within normal institutional limits
  9. Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate less than 5% per year) from the screening visit through 28 days after the last dose of study drug. Women of childbearing potential must have a negative pregnancy test at screening.

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

Exclusion Criteria
  1. Radiotherapy within 4 weeks or less prior to starting first veledimex dose
  2. Subjects with clinically significant increased intracranial pressure or uncontrolled seizures.
  3. Known immunosuppressive disease, autoimmune conditions, and /or chronic viral infections
  4. Use of systemic antibacterials, antifungals or antivirals for the treatment of acute clinically significant infection within 2 weeks of first veledimex dose. Concomitant therapy for chronic infections is not allowed. Subjects must be afebrile prior to Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is permitted perioperatively.
  5. Use of enzyme-inducing anti-epileptic drugs (EIAED) within 7 days prior to the first dose of study drug.
  6. Other concurrent clinically active malignant disease, requiring treatment, with the exception of non-melanoma cancers of the skin or carcinoma in-situ of the cervix or non-metastatic prostate cancer.
  7. Nursing or pregnant females
  8. Prior exposure to veledimex
  9. Use of medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first veledimex dosing
  10. Presence of any contra-indication for a neurosurgical procedure
  11. Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator or medical monitor, jeopardize the safety of a subject and/or their compliance with the protocol.

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

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