Malignant GliomaPhase 1ACTIONNCT03334305
Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas
A Phase 1 study testing TTRNA-DC vaccines with GM-CSF, Dose-intensified TMZ and Autologous Hematopoietic Stem cells (HSCs) in people with Malignant Glioma and High Grade Glioma, run by University of Florida at 3 sites in United States.
Trial summary
It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Malignant Glioma, High Grade Glioma
- What is being tested?
- TTRNA-DC vaccines with GM-CSF, Dose-intensified TMZ and Autologous Hematopoietic Stem cells (HSCs)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesUnited States
- Study dates
- 27 Aug 2018to 20 Mar 2025
- 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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- Pregnant or need to breast feed during the study period (Negative serum pregnancy test required).
- Known autoimmune or immunosuppressive disease or human immunodeficiency virus infection.
- Subjects with significant renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), pulmonary, hepatic or other organ dysfunction.
- Severe or unstable concurrent medical conditions.
- Prior allergic reaction to TMZ, GM-CSF, or Td
- Subjects who are unwilling or unable to receive treatment and undergo follow-up evaluations at the enrolled Sunshine Project Consortium treatment site.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Children's of Alabama at UAB
Birmingham, Alabama, 35233
UF Health Shands Children's Hospital
Gainesville, Florida, 32608
Children's National Hospital
Washington D.C., District of Columbia, 20010
About this study
Official title: ACTION Trial: Adoptive Cellular Therapy Following Dose-Intensified Temozolomide in Newly-diagnosed Pediatric High-grade Gliomas (Phase I).
It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. In most patients with advanced cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will use a patient's tumor to make a vaccine which we hope will stimulate T-cells to kill tumor cells and leave normal cells alone.
High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to attack. Before T-cells can become active against tumor cells, they require strong stimulation by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes, and create this strong stimulation.
The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC vaccines can be given safely. Most importantly, this study is also to determine whether the T-cells and DC vaccines can stimulate a person's immune system to fight off the tumor cells in the brain.
Read the detailed description
It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. But in most patients with advanced cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will use your tumor to make a vaccine which we hope will stimulate your T-cells to kill tumor cells and leave your normal cells alone.
High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to attack. Before T-cells can become active against tumor cells, they require strong stimulation by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes, and create this strong stimulation.
The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC vaccines can be given safely. Most importantly, this study is also to determine whether the T-cells and DC vaccines can stimulate your immune system to fight off the tumor cells in your brain. When the vaccine for this study is made, dendritic cells will be loaded with genetic material called RNA (ribonucleic acid) from your tumor to stimulate the dendritic cells. The vaccine has two components given at different times after chemoradiation and throughout chemotherapy cycles. The first part, the DC vaccine, involves RNA loaded dendritic cells that are given under the skin at several time points in the study and the second part, xALT vaccine, is a single infusion of tumor-specific T cells delivered through one of two peripheral IV catheters that are placed prior to infusion. This vaccine is investigational which means that it is not approved by the US Food and Drug Administration (FDA) and is being tested in research studies.
It is hoped that by injecting the DC vaccine into your skin and infusing the T-cells into your blood, your immune system will be activated against the tumor. Once it is activated against the tumor, your immune system may recognize and attack the tumor cells in your brain and not attack normal cells. Use of a vaccine that stimulates your immune system is called immunotherapy.
- Conditions
- Malignant Glioma, High Grade Glioma
- Being tested
- TTRNA-DC vaccines with GM-CSF, Dose-intensified TMZ, Autologous Hematopoietic Stem cells (HSCs), TTRNA-xALT, Td vaccine
- Keywords
- Immunotherapy, Pediatric, Vaccine Therapy, Young adult, Immune system, Dendritic Cell
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTRNA-DC vaccines with GM-CSFBiological
After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal.
Dose-intensified TMZDrug
After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations.
Autologous Hematopoietic Stem cells (HSCs)Biological
Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of > 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion.
TTRNA-xALTBiological
During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects.
Td vaccineDrug
A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) Receives: Biological: TTRNA-DC vaccines with GM-CSF; Drug: Dose-intensified TMZ; Biological: TTRNA-xALT; Drug: Td vaccine |
| Group B | Experimental | Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) Receives: Biological: TTRNA-DC vaccines with GM-CSF; Drug: Dose-intensified TMZ; Biological: Autologous Hematopoietic Stem cells (HSCs); Biological: TTRNA-xALT; Drug: Td vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate Safety of TTRNA-DCs and TTRNA-xALT
Percentage of subjects with grade 3 or greater adverse events. Adverse events (AEs) were summarized in the safety population (N = 5) at the participant level. For each AE term, a participant was counted once using the maximum observed CTCAE grade. Recurrent occurrences of the same AE in a participant were not counted multiple times.
Measured: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death, whichever occurs first, up to 10 months
Secondary outcomes (4)
Determine Feasibility of Completing Treatment
Number of subjects completing treatment. Completion defined as receipt of ≥3 DC vaccinations.
Measured: Up to 10 months
Change in CD4:CD8 T-cell Ratio
Change in CD4:CD8 T-cell ratio from baseline to post-treatment immune assessment measured in peripheral blood samples.
Measured: baseline to up to 10 months after initiation of treatment
Progression-free Survival (PFS)
Median time to progression
Measured: From date of first treatment until documented disease progression or death, assessed during study follow-up (up to approximately 3 years)
Overall Survival (OS)
Median time to death
Measured: From date of first treatment until death from any cause, assessed during study follow-up (up to approximately 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start27 Aug 2018
- Primary completion20 Mar 2025
- Study completion20 Mar 2025
Why it stopped: due to lack of accrual/feasibility to complete accrual due to competing trials
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 Malignant GliomaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Pediatric Cancer Foundation, National Cancer Institute (NCI), Moffitt Clinical Research Network (MCRN), National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Elias Sayour, MD, PhD, Principal investigator, University of FloridaDuane Mitchell, MD, PhD, Study chair, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03334305
- Sponsor's protocol ID
- IRB201701867-N
- Other IDs
- R01CA195563, OCR15852
- Acronym
- ACTION
- Status last verified
- Jan 2026
- First submitted
- 26 Oct 2017
- Last updated
- 23 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ACTION Trial: Adoptive Cellular Therapy Following Dose-Intensified Temozolomide in Newly-diagnosed Pediatric High-grade Gliomas (Phase I).
- ClinicalTrials.gov ID
- NCT03334305
- Acronym / sponsor ID
- ACTION / IRB201701867-N
- Conditions
- Malignant Glioma, High Grade Glioma
- Keywords
- Immunotherapy, Pediatric, Vaccine Therapy, Young adult, Immune system, Dendritic Cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to lack of accrual/feasibility to complete accrual due to competing trials
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- National Pediatric Cancer Foundation, National Cancer Institute (NCI), Moffitt Clinical Research Network (MCRN), National Institutes of Health (NIH)
- Study start
- 27 Aug 2018 (actual)
- Primary completion
- 20 Mar 2025 (actual)
- Study completion
- 20 Mar 2025 (actual)
- First posted
- 7 Nov 2017 (actual)
- Results
- Posted 23 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. In most patients with advanced cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will use a patient's tumor to make a vaccine which we hope will stimulate T-cells to kill tumor cells and leave normal cells alone.
High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to attack. Before T-cells can become active against tumor cells, they require strong stimulation by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes, and create this strong stimulation.
The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC vaccines can be given safely. Most importantly, this study is also to determine whether the T-cells and DC vaccines can stimulate a person's immune system to fight off the tumor cells in the brain.
Detailed description
It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. But in most patients with advanced cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will use your tumor to make a vaccine which we hope will stimulate your T-cells to kill tumor cells and leave your normal cells alone.
High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to attack. Before T-cells can become active against tumor cells, they require strong stimulation by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes, and create this strong stimulation.
The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC vaccines can be given safely. Most importantly, this study is also to determine whether the T-cells and DC vaccines can stimulate your immune system to fight off the tumor cells in your brain. When the vaccine for this study is made, dendritic cells will be loaded with genetic material called RNA (ribonucleic acid) from your tumor to stimulate the dendritic cells. The vaccine has two components given at different times after chemoradiation and throughout chemotherapy cycles. The first part, the DC vaccine, involves RNA loaded dendritic cells that are given under the skin at several time points in the study and the second part, xALT vaccine, is a single infusion of tumor-specific T cells delivered through one of two peripheral IV catheters that are placed prior to infusion. This vaccine is investigational which means that it is not approved by the US Food and Drug Administration (FDA) and is being tested in research studies.
It is hoped that by injecting the DC vaccine into your skin and infusing the T-cells into your blood, your immune system will be activated against the tumor. Once it is activated against the tumor, your immune system may recognize and attack the tumor cells in your brain and not attack normal cells. Use of a vaccine that stimulates your immune system is called immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Biological: TTRNA-DC vaccines with GM-CSF, Drug: Dose-intensified TMZ, Biological: TTRNA-xALT, Drug: Td vaccineDose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) |
| Group B | Experimental | Biological: TTRNA-DC vaccines with GM-CSF, Drug: Dose-intensified TMZ, Biological: Autologous Hematopoietic Stem cells (HSCs), Biological: TTRNA-xALT, Drug: Td vaccineDose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- Pregnant or need to breast feed during the study period (Negative serum pregnancy test required).
- Known autoimmune or immunosuppressive disease or human immunodeficiency virus infection.
- Subjects with significant renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), pulmonary, hepatic or other organ dysfunction.
- Severe or unstable concurrent medical conditions.
- Prior allergic reaction to TMZ, GM-CSF, or Td
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 |
|---|---|---|
| TTRNA-DC vaccines with GM-CSFAfter chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. | Biological | Group A, Group B |
| Dose-intensified TMZAfter chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. | Drug | Group A, Group B |
| Autologous Hematopoietic Stem cells (HSCs)Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of > 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. | Biological | Group B |
| TTRNA-xALTDuring TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. | Biological | Group A, Group B |
| Td vaccineA full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8. | Drug | Group A, Group B |
Primary outcome
Evaluate Safety of TTRNA-DCs and TTRNA-xALT
Time frame: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death, whichever occurs first, up to 10 months
Percentage of subjects with grade 3 or greater adverse events. Adverse events (AEs) were summarized in the safety population (N = 5) at the participant level. For each AE term, a participant was counted once using the maximum observed CTCAE grade. Recurrent occurrences of the same AE in a participant were not counted multiple times.
4 secondary outcomes
Determine Feasibility of Completing Treatment
Time frame: Up to 10 months
Change in CD4:CD8 T-cell Ratio
Time frame: baseline to up to 10 months after initiation of treatment
Progression-free Survival (PFS)
Time frame: From date of first treatment until documented disease progression or death, assessed during study follow-up (up to approximately 3 years)
Overall Survival (OS)
Time frame: From date of first treatment until death from any cause, assessed during study follow-up (up to approximately 3 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Elias Sayour, MD, PhD principal investigator
University of Florida
Duane Mitchell, MD, PhD study chair
University of Florida
3 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 TTRNA-DC vaccines with GM-CSF, Dose-intensified TMZ and Autologous Hematopoietic Stem cells (HSCs) in people with Malignant Glioma and High Grade Glioma, run by University of Florida at 3 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 0 inclusion and 6 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: stopped early, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 23 Apr 2026). 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?
Evaluate Safety of TTRNA-DCs and TTRNA-xALT (time frame: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death, whichever occurs first, up to 10 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Apr 2026.