A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors or DIPG

Status: Recruiting
Phase:
DFCI Protocol ID: 17-337

This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex for production of human 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 and may interfere with blood flow to the tumor. The main purpose of this study is to evaluate the safety and tolerability of a single tumor injection of Ad-RTS-hIL-12 given with oral veledimex in the pediatric population.

Conducting Institutions:

Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Mark Kieran, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Contacts:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria:

  1. Male or female subjects ≤ 21 years-of-age with the demonstrated ability to swallow
     capsules whole and who are willing to provide access to previously obtained biopsy
     results

  2. Provision of written informed consent and assent, when applicable, for tumor
     resection, stereotactic surgery, tumor biopsy, sample collection, and/or treatment
     with study drug prior to undergoing any study-specific procedures

  3. Arm 1: Evidence of recurrent or progressive supratentorial tumor, which has shown a >
     25% increase in bi dimensional measurements by MRI or is refractory with significant
     neuro deterioration that is not otherwise explained with no known curative therapy.

     Arm 2: Clinical presentation of DIPG and compatible MRI with approximately 2/3 of the
     pons included. Subject should be ≥ 2 weeks and ≤ 10 weeks post standard focal
     radiotherapy (ie, dose of 5400 to 5960 cGy and maximum dexamethasone of 1 mg/m2/day)

  4. At the time of registration, subjects must have recovered from the toxic effects of
     previous treatments, as determined by the treating physician.

       1. Targeted agents, including small-molecular tyrosine kinase inhibitors: 2 weeks

       2. Other cytotoxic agents: 3 weeks

       3. Nitrosoureas: 6 weeks

       4. Monoclonal antibody immunotherapies (eg, PD-1, CTLA-4): 6 weeks

       5. Vaccine-based and/or viral therapy: 3 months

  5. On a stable or decreasing dose of dexamethasone for the previous 7 days

  6. Able to undergo standard MRI scans with contrast agent before enrollment and after
     treatment

  7. Have age-appropriate functional performance:

       1. Lansky score ≥ 50 or

       2. Karnofsky score > 50 or

       3. Eastern Cooperative Oncology Group (ECOG) score ≤ 2

  8. Have adequate bone marrow reserves and liver and kidney function, as assessed by the
     following laboratory requirements:

       1. Hemoglobin ≥ 8 g/L

       2. Absolute lymphocyte count ≥ 500/mm3

       3. Absolute neutrophil count ≥ 1000/mm3

       4. Platelets ≥ 100,000/mm3 (untransfused [> 5 days] without growth factors)

       5. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age

       6. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for age

       7. Total bilirubin < 1.5 x ULN for age

       8. International normalized ratio (INR) and activated thromboplastin time within
  normal institutional limits

  9. Male and female subjects of childbearing potential must agree to use a highly reliable
     method of birth control (expected failure rate < 1% 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.

Exclusion Criteria:

  1. Radiotherapy treatment prior to the first veledimex dose:

       1. Focal radiation ≤ 4 weeks

       2. Whole-brain radiation ≤ 6 weeks

       3. Cranio-spinal radiation ≤ 12 weeks NOTE: Subjects in Arm 2 (ie, with DIPG) must
  be ≥ 2 weeks and ≤ 10 weeks after standard focal radiotherapy (dose of 5400 to
  5960 cGy and maximum dexamethasone of 1 mg/m2/day)

  2. Subjects with clinically significant increased intracranial pressure (eg, impending
     herniation or requirement for immediate palliative treatment) or uncontrolled seizures

  3. Subjects whose body surface area (BSA) would expose them to < 75% or > 125% of the
     target dose

  4. Known immunosuppressive disease, autoimmune condition, and/or chronic viral infection
     (eg, human immunodeficiency virus [HIV], hepatitis)

  5. Use of systemic antibacterial, antifungal, or antiviral medications 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 allowed
     perioperatively

  6. Use of enzyme-inducing antiepileptic drugs (EIAEDs) within 7 days prior to the first
     dose of study drug

  7. Other concurrent clinically active malignant disease, requiring treatment

  8. Nursing or pregnant females

  9. Prior exposure to veledimex

 10. Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450)
     3A4 within 7 days prior to veledimex

 11. Use of heparin or acetylsalicylic acid (ASA)

 12. Presence of any contraindication for a neurosurgical procedure

 13. Unstable or clinically significant concurrent medical condition

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