Glioblastoma MultiformePhase 1NCT02026271
A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma
A Phase 1 study testing Ad-RTS-hIL-12 and veledimex in people with Glioblastoma Multiforme and Anaplastic Oligoastrocytoma, run by Alaunos Therapeutics at 6 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 18 to 75 years
- Conditions the study is for
- Glioblastoma Multiforme, Anaplastic Oligoastrocytoma
- What is being tested?
- Ad-RTS-hIL-12 and veledimex
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 6 sitesUnited States
- Study dates
- Jun 2015to Aug 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects ≥ 18 and ≤ 75 years of age
- 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
- Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue.
- Evidence of tumor recurrence/progression by MRI (RANO criteria) post standard initial therapy.
- Previous standard of care anti-tumor treatment including surgery and/or biopsy and chemoradiation. The washout periods from prior therapies are intended as follows:
- Nitrosoureas: 6 weeks
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- Other cytotoxic agents: 4 weeks
- Anti-angiogenic agents including bevacizumab: 4 weeks
- Targeted agents including small-molecule tyrosine kinase inhibitors: 2 weeks
- Experimental immunotherapies: 3 months
- Vaccine based therapy: 3 months
- Able to undergo standard MRI scans with contrast agent
- Karnofsky Performance Status ≥ 70
- Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
- Hemoglobin ≥ 9 g/L
- Lymphocytes > 500/ mm3
- Absolute Neutrophil Count ≥ 1500/ mm3
- Platelets ≥ 100,000/ mm3
- Serum creatinine ≤ 1.5 x ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤ 5 × ULN
- Total bilirubin < 1.5 x ULN
- International Normalized Ratio (INR) and activated Partial Thromboplastin Time [PTT] within normal institutional limits
- 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.
Who cannot join
- Radiotherapy within 4 weeks or less prior to starting first veledimex dose
- Subjects with clinically significant increased intracranial pressure or uncontrolled seizures.
- Known immunosuppressive disease, autoimmune conditions, and /or chronic viral infections
- 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.
- Use of enzyme-inducing anti-epileptic drugs (EIAED) within 7 days prior to the first dose of study drug.
- 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.
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- Nursing or pregnant females
- Prior exposure to veledimex
- Use of medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first veledimex dosing
- Presence of any contra-indication for a neurosurgical procedure
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Brigham & Women's
Boston, Massachusetts, 02115
Northwestern
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
MD Anderson Cancer Center
Houston, Texas, 77030
Cedars-Sinai
Los Angeles, California, 90048
University of California - San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase I Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma
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.
Read the detailed description
Eligible patients will be stratified to one of two groups, according to clinical indication for tumor resection. Patients who are scheduled for a standard of care 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.
Patients not scheduled for tumor resection 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, veledimex
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad-RTS-hIL-12Biological
Also called INXN-2001
- 2.0 x 10^11 viral particles (vp) per injection or 1.0 x 10^12 viral particles (vp) per injection
- one intratumoral injection of Ad-RTS-hIL-12
veledimexDrug
Also called INXN-1001, Activator Ligand
- 4 doses (20mg/day, 40mg/day, 80mg/day, and 120mg/day)
- 14 oral daily doses of veledimex
- 1 Expansion cohort at a single dose level at or below MTD
| Study group | Role | What they receive |
|---|---|---|
| Ad-RTS-hIL-12+veledimex | Experimental | varying doses of intratumoral Ad-RTS-hIL-12 (INXN-2001) and oral veledimex (activator ligand). Receives: Biological: Ad-RTS-hIL-12; Drug: veledimex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of Varying Doses of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex Doses in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma
Evaluation will be based on the incidence, intensity, and type of Adverse Events (AEs). Clinically significant changes in the subjects' physical examinations, vital signs, and ECG evaluations, and clinical manifestations relevant to abnormal laboratory values will be captured as AEs.
Measured: 3 years
Secondary outcomes (7)
Veledimex Maximum Tolerated Dose (MTD) When Given With Varying Doses of Intratumoral Ad-RTS-hIL-12
The protocol defined the MTD as the dose level below at which less than 33% of subjects, of the same cohort in a group, experienced DLTs, with an independent assessment of Group 1 and Group 2 subjects.
- The number of DLTs and the proportion of subjects with any DLT and each type of DLT were summarized by veledimex dose within each group.
Measured: 3 years
Veledimex Pharmacokinetic Profile and Veledimex Concentration Ratio Between the Brain Tumor and the Blood
From the protocol: Veledimex PK parameters to be determined will include, but are not limited to, the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), half-life (t1/2), area-under-the-concentration versus time curve (AUC), volume of distribution (Vd), and clearance (CL).
From the SAP: The PK blood sample collection was performed either pre-dose or 3-5 hours post-dose, therefore only Cmax and Ctrough will be summarized and plotted. Veledimex concentration ratio between brain tumor and blood will be assessed on Day 0 samples. There will be no parameters including time to maximum plasma concentration (Tmax), half-life (t1/2), area under the curve (AUC), volume of distribution (Vd), and clearance (CL). Cmax will be determined from the maximum plasma concentration from Day 0 (post veledimex and resection/craniotomy), 3-5 hours after the veledimex dose on Day 1, and 3-5 hours after the veledimex dose on Day 14.
Measured: 15 days
Cellular and Humoral Immune Responses Elicited by Ad-RTS-hIL-12 and Veledimex
Peak serum IL-12 and I downstream IFN-gamma expressions between Day 3 to Day 28 are reported by dose cohort.
Measured: 28 days
Tumor Objective Response Rate (ORR)
For the ORR calculation, responders are defined as those experiencing a confirmed complete response or confirmed partial response. Non-responders are those either with stable or progressive disease. Those subjects that cannot be assessed will be treated as non-responders for the purposes of deriving the percentage of responders and confidence intervals. The ORR is reported overall by treatment arm based on the investigator response at timepoints 56 days, Week 16, Week 24, and Week 48.
Measured: 48 weeks
Progression-free Survival (PFS)
PFS (progression free survival) is the time in months from the first treatment (either veledimex or Ad-RTS-hIL-12) to the first assessment on which the overall response is reported as disease progression. Subjects withdrawing from the study will be censored at their last non progressive disease response assessment. If a subject does not have a non-progressive disease response assessment, the subject will be censored on the date of the first treatment as described above.
Measured: 3 years
Overall Survival (OS)
OS is defined as the duration of time from the first dose of study drug (Day 0) to the date of death from any cause in days or months. Subjects are censored based on the last date known to be alive. For example:
- Subjects who discontinue the study without documentation of additional follow-up will be censored at the date of discontinuation.
- Subjects who are lost to follow-up will be censored at last follow-up contact date.
- Subjects still alive up to 2 years from the first dose of study drug are classified as censored and as having completed all follow-up scheduling.
Measured: 6, 9, 12, 15, 18, and 24 months
Veledimex Concentration Ratio Between the Brain Tumor and the Blood
From the protocol: Veledimex PK parameters to be determined will include, but are not limited to, the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), half-life (t1/2), area-under-the-concentration versus time curve (AUC), volume of distribution (Vd), and clearance (CL).
From the SAP: The PK blood sample collection was performed either pre-dose or 3-5 hours post-dose, therefore only Cmax and Ctrough will be summarized and plotted. Veledimex concentration ratio between brain tumor and blood will be assessed on Day 0 samples. There will be no parameters including time to maximum plasma concentration (Tmax), half-life (t1/2), area under the curve (AUC), volume of distribution (Vd), and clearance (CL). Cmax will be determined from the maximum plasma concentration from Day 0 (post veledimex and resection/craniotomy), 3-5 hours after the veledimex dose on Day 1, and 3-5 hours after the veledimex dose on Day 14.
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2014 (estimated)
- Study startJun 2015
- Primary completionAug 2019
- Study completionAug 2019
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 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
- NCT02026271
- Sponsor's protocol ID
- ATI001-102
- Status last verified
- Mar 2025
- First submitted
- 16 Dec 2013
- Last updated
- 16 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Chiocca EA, Yu JS, Lukas RV, Solomon IH, Ligon KL, Nakashima H, Triggs DA, Reardon DA, Wen P, Stopa BM, Naik A, Rudnick J, Hu JL, Kumthekar P, Yamini B, Buck JY, Demars N, Barrett JA, Gelb AB, Zhou J, Lebel F, Cooper LJN. Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial. Sci Transl Med. 2019 Aug 14;11(505):eaaw5680. doi: 10.1126/scitranslmed.aaw5680.
PubMed 31413142
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma
- ClinicalTrials.gov ID
- NCT02026271
- Acronym / sponsor ID
- ATI001-102
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Alaunos TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2015
- Primary completion
- Aug 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 1 Jan 2014 (estimated)
- Results
- Posted 16 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Eligible patients will be stratified to one of two groups, according to clinical indication for tumor resection. Patients who are scheduled for a standard of care 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.
Patients not scheduled for tumor resection 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ad-RTS-hIL-12+veledimex | Experimental | Biological: Ad-RTS-hIL-12, Drug: veledimexvarying doses of intratumoral Ad-RTS-hIL-12 (INXN-2001) and oral veledimex (activator ligand). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Male or female subjects ≥ 18 and ≤ 75 years of age
- 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
- Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue.
- Evidence of tumor recurrence/progression by MRI (RANO criteria) post standard initial therapy.
- Previous standard of care anti-tumor treatment including surgery and/or biopsy and chemoradiation. The washout periods from prior therapies are intended as follows:
Key exclusion criteria (11 listed)
- Radiotherapy within 4 weeks or less prior to starting first veledimex dose
- Subjects with clinically significant increased intracranial pressure or uncontrolled seizures.
- Known immunosuppressive disease, autoimmune conditions, and /or chronic viral infections
- 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.
- Use of enzyme-inducing anti-epileptic drugs (EIAED) within 7 days prior to the first dose of study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ad-RTS-hIL-12Also: INXN-2001* 2.0 x 10^11 viral particles (vp) per injection or 1.0 x 10^12 viral particles (vp) per injection * one intratumoral injection of Ad-RTS-hIL-12 | Biological | Ad-RTS-hIL-12+veledimex |
| veledimexAlso: INXN-1001, Activator Ligand* 4 doses (20mg/day, 40mg/day, 80mg/day, and 120mg/day) * 14 oral daily doses of veledimex * 1 Expansion cohort at a single dose level at or below MTD | Drug | Ad-RTS-hIL-12+veledimex |
Primary outcome
Safety and Tolerability of Varying Doses of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex Doses in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma
Time frame: 3 years
Evaluation will be based on the incidence, intensity, and type of Adverse Events (AEs). Clinically significant changes in the subjects' physical examinations, vital signs, and ECG evaluations, and clinical manifestations relevant to abnormal laboratory values will be captured as AEs.
7 secondary outcomes
Veledimex Maximum Tolerated Dose (MTD) When Given With Varying Doses of Intratumoral Ad-RTS-hIL-12
Time frame: 3 years
Veledimex Pharmacokinetic Profile and Veledimex Concentration Ratio Between the Brain Tumor and the Blood
Time frame: 15 days
Cellular and Humoral Immune Responses Elicited by Ad-RTS-hIL-12 and Veledimex
Time frame: 28 days
Tumor Objective Response Rate (ORR)
Time frame: 48 weeks
Progression-free Survival (PFS)
Time frame: 3 years
Overall Survival (OS)
Time frame: 6, 9, 12, 15, 18, and 24 months
Veledimex Concentration Ratio Between the Brain Tumor and the Blood
Time frame: 15 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31413142Chiocca EA, Yu JS, Lukas RV, Solomon IH, Ligon KL, Nakashima H, Triggs DA, Reardon DA, Wen P, Stopa BM, Naik A, Rudnick J, Hu JL, Kumthekar P, Yamini B, Buck JY, Demars N, Barrett JA, Gelb AB, Zhou J, Lebel F, Cooper LJN. Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial. Sci Transl Med. 2019 Aug 14;11(505):eaaw5680. doi: 10.1126/scitranslmed.aaw5680.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaymes Holland study director
Alaunos Therapeutics
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ad-RTS-hIL-12 and veledimex in people with Glioblastoma Multiforme and Anaplastic Oligoastrocytoma, run by Alaunos Therapeutics at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of Varying Doses of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex Doses in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02026271, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2025.