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

A Phase I/II Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Pediatric Brain Tumor Subjects

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.

Study Overview

• Status: Terminated
• Conditions: Diffuse Intrinsic Pontine Glioma; Pediatric Brain Tumor
• Intervention / Treatment: Biological: Ad-RTS-hIL-12; Drug: Oral Veledimex - Arm 1 (Pediatric Brain Tumor); Drug: Oral Veledimex - Arm 2 (DIPG)

Detailed Description

Eligible patients will be stratified to one of two arms, according to clinical indication for tumor resection. Pediatric patients who are scheduled for craniotomy and tumor resection will receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12 will be administered by free-hand injection. Patients will continue on oral veledimex for 14 days. This arm has been completed and is currently closed to enrollment.

Pediatric patients with diffuse intrinsic pontine glioma (DIPG) will receive Ad-RTS-hIL-12 by stereotactic injection and then will continue on oral veledimex for 14 days.

The study is divided into three periods: the screening period, the treatment period and the follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco, Benioff Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana- Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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, not in direct continuity with the ventricular system (e.g., there is physical separation between the tumor and ventricle, the tumor does not open directly into the ventricular system).

   Arm 2: Clinical presentation of DIPG and compatible MRI with approximately 2/3 of the pons included and without evidence of dissemination. Subjects 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 ≥ 40 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). The use of systemic heparinization, or any ASA containing medications, is prohibited during active dosing with veledimex. Prophylactic heparin SC, per institutional protocol, or heparin when used for maintaining patency of an access port of a PICC line is permitted.
12. Presence of any contraindication for a neurosurgical procedure
13. Unstable or clinically significant concurrent medical condition that would jeopardize the safety of a subject and/or their compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - Closed; Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.	Biological: Ad-RTS-hIL-12; 2.0 x 10^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12; Drug: Oral Veledimex - Arm 1 (Pediatric Brain Tumor); 1 dose level (10mg/day) 15 oral daily doses of veledimex
Experimental: Arm 2 - Open; Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.	Biological: Ad-RTS-hIL-12; 2.0 x 10^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12; Drug: Oral Veledimex - Arm 2 (DIPG); 2 dose levels (10mg/day, 20mg/day) 14 oral daily doses of veledimex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.	Dose Limiting Toxicities are defined as events that occur during the first 28 days (Day 0 - Day 28) that meets one of the following criteria: Any local reaction that requires operative intervention and is felt to be attributable to study drug; Any local reaction that has life-threatening consequences requiring urgent intervention or results in death and is felt to be attributable to study drug; Any Grade 3 or higher non-hematologic adverse event that is at least possibly related to study drug and lasts ≥ 3 days; Nausea and vomiting will not be considered a DLT unless at least Grade 3 and refractory to antiemetics; Grade 3 or higher thrombocytopenia (< 50,000/mm3) at least possibly related to study drug; Any Grade 4 hematologic toxicity (except thrombocytopenia) that is at least possibly related to study drug and lasts ≥ 5 days; Transient neurological changes are expected in Arm 2 and will not be considered a DLT unless they last > 10 days	From Day 0 through Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method	Veledimex brain concentration. Veledimex plasma concentration was below the limit of quantitation for most patients. Given the limited number of subjects enrolled and early closure of the study, complete assessment of veledimex in blood and brain tumor could not be determined.	From Day 0 through Day 15 of veledimex dosing
Overall Survival (OS)	OS is defined as the duration of time from the first dose of the study drug to the date of death. Subjects were followed for up to 2 years.	2 Years
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels	Samples for serum cytokine analysis were collected on Days 0, 3, 7, 14, and 28. For the results, participants who had samples analyzed were included in the "number analyzed" counts; however, values that were below the limit of quantitation (BLQ) were excluded from the calculation of mean and standard deviation.	Day 0, Day 3, Day 7, Day 14, and Day 28
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0	Subjects with Ad-RTS-hIL-12 and veledimex related adverse events will be assessed for safety by CTCAE v5.0	2 Years
Best Overall Response by iRANO Criteria	Best Overall Response was assessed using the immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria.	2 Years
Duration of Response (DOR)	Duration of Response (DOR) was defined as the time from the first documentation of a Complete Response (CR) or Partial Response (PR) to the first documentation of Progressive Disease (PD) or death due to any cause, whichever occurred first.	From the time of first response (CR or PR) until progression or death

Collaborators and Investigators

• Sponsor: Alaunos Therapeutics
• Investigators: Study Director: Jaymes Holland, Alaunos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2017
• Primary Completion (Actual): September 10, 2021
• Study Completion (Actual): September 10, 2021

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 10, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Glioblastoma; DIPG; Anaplastic Astrocytoma; High Grade Glioma (HGG) Not Otherwise Specified (NOS); Supratentorial Tumor NOS
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Stem Neoplasms; Infratentorial Neoplasms; Diffuse Intrinsic Pontine Glioma; Brain Neoplasms
• Other Study ID Numbers: ATI001-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No