Pediatric Brain TumorPhase 1/2NCT03330197
A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG
A Phase 1/2 study testing Ad-RTS-hIL-12, Oral Veledimex - Arm 1 (Pediatric Brain Tumor) and Oral Veledimex - Arm 2 (DIPG) in people with Pediatric Brain Tumor and Diffuse Intrinsic Pontine Glioma, run by Alaunos Therapeutics at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 21 years
- Conditions the study is for
- Pediatric Brain Tumor, Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Ad-RTS-hIL-12, Oral Veledimex - Arm 1 (Pediatric Brain Tumor) and Oral Veledimex - Arm 2 (DIPG)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesUnited States
- Study dates
- 26 Sep 2017to 10 Sep 2021
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
- Eastern Cooperative Oncology Group (ECOG) score ≤ 2
- Have adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
- Hemoglobin ≥ 8 g/L
- Absolute lymphocyte count ≥ 500/mm3
- Absolute neutrophil count ≥ 1000/mm3
- Platelets ≥ 100,000/mm3 (untransfused [> 5 days] without growth factors)
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for age
- Total bilirubin < 1.5 x ULN for age
- International normalized ratio (INR) and activated thromboplastin time within normal institutional limits
- 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.
Who cannot join
- 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
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- 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
- Unstable or clinically significant concurrent medical condition that would jeopardize the safety of a subject and/or their compliance with the protocol
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Dana- Farber Cancer Institute
Boston, Massachusetts, 02215
Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University of California San Francisco, Benioff Children's Hospital
San Francisco, California, 94158
About this study
Official title: 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.
Read the 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.
- Being tested
- Ad-RTS-hIL-12, Oral Veledimex - Arm 1 (Pediatric Brain Tumor), Oral Veledimex - Arm 2 (DIPG)
- Keywords
- DIPG, Glioblastoma, Anaplastic Astrocytoma, High Grade Glioma (HGG) Not Otherwise Specified (NOS), Supratentorial Tumor NOS
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma, Glioblastoma, Astrocytoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad-RTS-hIL-12Biological
2.0 x 10^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor)Drug
1 dose level (10mg/day) 15 oral daily doses of veledimex
Oral Veledimex - Arm 2 (DIPG)Drug
2 dose levels (10mg/day, 20mg/day) 14 oral daily doses of veledimex
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Ad-RTS-hIL-12; Drug: Oral Veledimex - Arm 2 (DIPG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From Day 0 through Day 56
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 2 Years
Best Overall Response by iRANO Criteria
Best Overall Response was assessed using the immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria.
Measured: 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.
Measured: From the time of first response (CR or PR) until progression or death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start26 Sep 2017
- Primary completion10 Sep 2021
- Study completion10 Sep 2021
Why it stopped: Sponsor decision due to slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pediatric Brain TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alaunos Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jaymes Holland, Study director, Alaunos Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03330197
- Sponsor's protocol ID
- ATI001-103
- Status last verified
- Aug 2025
- First submitted
- 16 Oct 2017
- Last updated
- 12 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided