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

NCT03330197 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: ATI001-103
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Pediatric Brain Tumor; Diffuse Intrinsic Pontine Glioma

Keywords

DIPG; Glioblastoma; Anaplastic Astrocytoma; High Grade Glioma (HGG) Not Otherwise Specified (NOS); Supratentorial Tumor NOS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method

  From Day 0 through Day 15 of veledimex dosing

• Overall Survival (OS)

  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

  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

  2 Years

• Best Overall Response by iRANO Criteria

  2 Years

Study Arms (2)

Arm 1 - Closed

EXPERIMENTAL

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; Drug: Oral Veledimex - Arm 1 (Pediatric Brain Tumor)

Arm 2 - Open

EXPERIMENTAL

Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.

Biological: Ad-RTS-hIL-12; Drug: Oral Veledimex - Arm 2 (DIPG)

Interventions

Ad-RTS-hIL-12 BIOLOGICAL

2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12

Arm 1 - Closed; Arm 2 - Open

Oral Veledimex - Arm 1 (Pediatric Brain Tumor) DRUG

1 dose level (10mg/day) 15 oral daily doses of veledimex

Arm 1 - Closed

Oral Veledimex - Arm 2 (DIPG) DRUG

2 dose levels (10mg/day, 20mg/day) 14 oral daily doses of veledimex

Arm 2 - Open

Eligibility Criteria

• Age: 0 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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
• 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)
• At the time of registration, subjects must have recovered from the toxic effects of previous treatments, as determined by the treating physician.
• Targeted agents, including small-molecular tyrosine kinase inhibitors: 2 weeks
• Other cytotoxic agents: 3 weeks
• Nitrosoureas: 6 weeks
• Monoclonal antibody immunotherapies (eg, PD-1, CTLA-4): 6 weeks
• Vaccine-based and/or viral therapy: 3 months
• On a stable or decreasing dose of dexamethasone for the previous 7 days
• Able to undergo standard MRI scans with contrast agent before enrollment and after treatment
• Have age-appropriate functional performance:
• Lansky score ≥ 40 or
• Karnofsky score \> 50 or

You may not qualify if:

• Radiotherapy treatment prior to the first veledimex dose:
• Focal radiation ≤ 4 weeks
• Whole-brain radiation ≤ 6 weeks
• 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)
• Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures
• Subjects whose body surface area (BSA) would expose them to \< 75% or \> 125% of the target dose
• Known immunosuppressive disease, autoimmune condition, and/or chronic viral infection (eg, human immunodeficiency virus \[HIV\], hepatitis)
• 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
• Use of enzyme-inducing antiepileptic drugs (EIAEDs) within 7 days prior to the first dose of study drug
• Other concurrent clinically active malignant disease, requiring treatment
• Nursing or pregnant females
• Prior exposure to veledimex
• Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450) 3A4 within 7 days prior to veledimex
• 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.
• Presence of any contraindication for a neurosurgical procedure

Sponsors & Collaborators

• Alaunos Therapeutics: lead

Study Sites (3)

University of California San Francisco, Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Dana- Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Glioblastoma; Astrocytoma; Glioma

Interventions

dipinacoline glutamate

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Given the limited number of subjects enrolled and early closure of the study, complete assessment of safety and tolerability could not be determined. There was a wide range of adverse events reported and limited survival among the subjects enrolled.

Results Point of Contact

• Title: Jaymes Holland
• Organization: Alaunos Therapeutics

jholland@alaunos.com

650 273-2627

Study Officials

• Jaymes Holland

  Alaunos Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2017
• First Posted: November 6, 2017
• Study Start: September 26, 2017
• Primary Completion: September 10, 2021
• Study Completion: September 10, 2021
• Last Updated: August 12, 2025
• Results First Posted: August 12, 2025

Record last verified: 2025-08

Locations

US (3)