Diffuse Intrinsic Pontine Glioma (DIPG)Phase 1BRAVONCT03396575
Brain Stem Gliomas Treated With Adoptive Cellular Therapy During Focal Radiotherapy Recovery Alone or With Dose-intensified Temozolomide (Phase I)
A Phase 1 study testing TTRNA-DC vaccines with GM-CSF, TTRNA-xALT and Cyclophosphamide + Fludarabine Lymphodepletive Conditioning in people with Diffuse Intrinsic Pontine Glioma (DIPG) and Brain Stem Glioma, run by University of Florida at 1 site in United States.
Trial summary
The standard of care for children with DIPG includes focal radiotherapy (RT) but outcomes have remained dismal despite this treatment. The addition of oral Temozolomide (TMZ) concurrently with RT followed by monthly TMZ was also found to be safe but ineffective. Read more about this study
- Who is it for?
- Ages 3 to 30 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma (DIPG), Brain Stem Glioma
- What is being tested?
- TTRNA-DC vaccines with GM-CSF, TTRNA-xALT and Cyclophosphamide + Fludarabine Lymphodepletive Conditioning
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2018to 20 Mar 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Initial Screening
- Radiologically confirmed DIPG or other diffuse intrinsic brain stem glioma (Grade III or IV).
- Patient and/or parents/guardian willing to consent to biopsy for obtaining tumor material for confirmatory diagnosis and/or tumor RNA extraction and amplification.
- Biopsy confirmation of any grade of glioma (for patients with classic DIPG on neuroimaging or at least grade III glioma in case of other diffuse intrinsic brain stem gliomas)
- Karnofsky Performance Status (KPS) of > 50% (KPS for > 16 years of age) or Lansky performance Score (LPS) of ≥ 50 (LPS for ≤ 16 years of age) assessed within 2 weeks prior to registration;
- Bone Marrow;
Show all 20Show fewer
- ANC (absolute neutrophil count) ≥ 1000/µl (unsupported)
- Platelets ≥ 100,000/µl (unsupported)
- Hemoglobin > 8 g/dL (can be transfused)
- Renal;
- Serum creatinine ≤ upper limit of institutional normal
- Hepatic;
- Bilirubin ≤ 1.5 times upper limit of institutional normal for age
- SGPT (ALT) ≤ 3 times upper limit of institutional normal for age
- SGOT (AST) ≤ 3 times upper limit of institutional normal for age
- Patients of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control while being treated on this study.
- Signed informed consent according to institutional guidelines.
- Post Biopsy
- Patients with post-surgical neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration;
- Pathologic diagnosis of glioma on tumor biopsy.
Who cannot join
- Patients with severe dysphagia, obtundation, or tetraplegia (poor risks for anesthesia and biopsy procedure);
- Absence of tumor on biopsy specimen;
- 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;
- Patients with significant renal, cardiac, pulmonary, hepatic or other organ dysfunction;
- Severe or unstable concurrent medical conditions;
Show all 11Show fewer
- Patients who require corticosteroids above physiologic doses (>4 mg/day dexamethasone) after chemoradiotherapy;
- Patients scheduled to receive any other concurrent anticancer or investigational drug therapy;
- Prior allergic reaction to TMZ, GM-CSF, or Td;
- Patients who are unwilling or unable to receive treatment and undergo follow-up evaluations at University of Florida;
- Patient and/or parent/guardian demonstrating an inability to comply with the study and/or follow-up procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
UF Health Shands Children's Hospital
Gainesville, Florida, 32610
About this study
Official title: BRAVO: Newly-Diagnosed Brain Stem Gliomas Treated With Adoptive Cellular Therapy During Recovery From Focal Radiotherapy Alone or Focal Radiotherapy and Dose-intensified Temozolomide (Phase I)
The standard of care for children with DIPG includes focal radiotherapy (RT) but outcomes have remained dismal despite this treatment. The addition of oral Temozolomide (TMZ) concurrently with RT followed by monthly TMZ was also found to be safe but ineffective. Recent studies in adults have shown that certain types of chemotherapy induce a profound but transient lymphopenia (low blood lymphocytes) and vaccinating and/or the adoptive transfer of tumor-specific lymphocytes into the cancer patient during this lymphopenic state leads to dramatic T cell expansion and potent immunologic and clinical responses. Therefore, patients in this study will either receive concurrent TMZ during RT and immunotherapy during and after maintenance cycles of dose-intensive TMZ (Group A) or focal radiotherapy alone and immunotherapy without maintenance DI TMZ (Group B). Immune responses during cycles of DC vaccination with or without DI TMZ will be evaluated in both treatment groups.
Read the detailed description
The standard of care for children with DIPG includes external beam focal radiotherapy (RT) but outcomes have remained dismal despite this treatment. The addition of oral Temozolomide (TMZ) concurrently with focal irradiation followed by maintenance monthly TMZ was also found to be safe but ineffective. However, in the context of an immunotherapy strategy, it might be beneficial to use TMZ as an adjuvant therapy during and following radiotherapy. Recent pre-clinical and clinical studies in adults with have shown that both myeloablative (MA) and non-myeloablative (NMA) chemotherapy induce a profound but transient lymphopenia and, somewhat counterintuitively, vaccination during recovery from this lymphopenic state and/or the adoptive transfer of tumor-specific lymphocytes into lymphodepleted hosts leads to dramatic in vivo T cell expansion and potent immunologic and clinical responses. Therefore, the study team expects that tumor-specific lymphocytes, expanded ex vivo with the use of TTRNA-pulsed DCs may provide a source of lymphocytes that preferentially expand in this lymphopenic environment following TMZ, and serve as a source of responder cells to subsequent DC vaccination.
TMZ induces profound lymphopenia in children with central nervous system (CNS) tumors. It has not been conclusively shown to help in augmenting vaccine-induced immune responses in this population. Patients in this study will either receive concurrent TMZ during RT and immunotherapy during and after maintenance cycles of dose-intensive TMZ (Group A) or focal radiotherapy alone and immunotherapy without maintenance DI TMZ (Group B). Immune responses during cycles of DC vaccination with or without DI TMZ will be evaluated in both treatment groups. The immunotherapy regimen will consist of TTRNA-DC vaccines alone followed by adoptive cellular therapy consisting of ex vivo expanded tumor-reactive lymphocytes coupled with TTRNA-DC vaccines and autologous HSCs.
Patients in Group B will not receive DI TMZ, however, they will receive lymphodepletion with cyclophosphamide + fludarabine after DC vaccination and prior to the intravenous infusion of ex vivo expanded tumor-reactive lymphocytes. T cell engraftment and persistence has been shown to be augmented by lymphodepletion in numerous studies. TTRNA-pulsed DCs will be given in conjunction with the adjuvants GM-CSF and tetanus-diphtheria toxoid (Td) vaccine which the study team have shown can significantly enhance clinical responses to DC vaccination.
- Being tested
- TTRNA-DC vaccines with GM-CSF, TTRNA-xALT, Cyclophosphamide + Fludarabine Lymphodepletive Conditioning, Dose-Intensified TMZ, Td vaccine
- Keywords
- Tumor mRNA-pulsed autologous Dendritic Cells (TTRNA-DCs), Tumor-specific autologous lymphocyte transfer (TTRNA-xALT), Autologous G-CSF mobilized HSCs, Temozolomide (TMZ), Cyclophosphamide (CTX), Fludarabine (Flu), Immunotherapy, Pediatric, Young Adult, Brain Tumor, CNS, Vaccine Therapy
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma, Xanthomatosis, Cerebrotendinous, Influenza, Human, Brain Neoplasms
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.
TTRNA-xALTBiological
During TMZ Cycle 4 and with DC vaccine #6, an infusion of T-cells will be administered to all subjects.
Cyclophosphamide + Fludarabine Lymphodepletive ConditioningDrug
Subjects in Group B, however, will receive lymphodepletion with cyclophosphamide + fludarabine after DC vaccination and prior to the intravenous infusion of ex vivo expanded tumor-reactive lymphocytes.
Dose-Intensified TMZDrug
After chemoradiation, subjects in Group A 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.
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.
Autologous Hematopoietic Stem Cells (HSC)Biological
During Cycle 4, all patients will receive HSCs prior to xALT infusion and DC vaccine #6.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) during cycles of Dose-intensified TMZ Receives: Biological: TTRNA-DC vaccines with GM-CSF; Biological: TTRNA-xALT; Drug: Dose-Intensified TMZ; Drug: Td vaccine; Biological: Autologous Hematopoietic Stem Cells (HSC) |
| Group B | Experimental | TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) with Cyclophosphamide + Fludarabine Lymphodepletive Conditioning Receives: Biological: TTRNA-DC vaccines with GM-CSF; Biological: TTRNA-xALT; Drug: Cyclophosphamide + Fludarabine Lymphodepletive Conditioning; Drug: Td vaccine; Biological: Autologous Hematopoietic Stem Cells (HSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility and safety of adoptive cellular therapy in pediatric patients with DIPG with or without dose-intensified TMZ during cycles of DC vaccination
Number of subjects with immunotherapy-related dose-limiting toxicities including 1) Grade III or greater non-neurologic toxicity; 2) Grade III neurologic toxicity that does not improve to Grade II or better within 5 days; or 3) Grade IV neurologic toxicity.
Measured: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death
Determine the maximally achievable dose (MAD) or maximum tolerated dose (MTD) of xALT plus DC and HSC in Group A and Group B subjects
The first 6 patients in Group A (receiving DI TMZ) at a dose of 3 x 107 cells /kg xALT and if dose-limiting toxicities are observed in no more than 1 of 6 patients, the study team will enroll another 6 patients at the next dose level of 3 x108 cells /kg. If no more than 1 patient suffers dose limiting toxicity (DLT) at this dose level, it will declared the MAD of T cells. Subjects enrolled in Group B will be treated at the MAD or MTD determined in the Group A Cohort.
Measured: From first DC vaccine in Group A until 14 days after administration of the last dose of investigational product is given.
Secondary outcomes (3)
Post-immunotherapy functional anti-tumor immune responses
The in vivo expansion, persistence, and function of tumor-specific lymphocytes will be followed serially in these patients using T-cell receptor (TCR) sequencing and functional immunologic analysis.
Measured: Up to 10 months
Analysis of progression-free survival (PFS)
Days of PFS
Measured: Up to 5 years
Analysis of overall survival (OS)
Days of OS
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2018
- Study start17 Jul 2018
- Primary completion20 Mar 2025
- Study completion20 Mar 2025
Why it stopped: Not feasible to accrue due to competing studies
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Intrinsic Pontine Glioma (DIPG)Studies 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
- Model description
- Patients in this study will either receive concurrent TMZ during RT and dose-intensive TMZ as maintenance treatment (Group A) or radiotherapy only prior to DC vaccination and without maintenance DI TMZ (Group B). Immune responses during cycles of DC vaccination with or without DI TMZ will be evaluated in both treatment groups. Once Group A accrual is completed and evaluated for toxicity, 6 Group B patients will be enrolled and treated at the Maximally Achievable Dose (MAD) or (Maximum Tolerated Dose) MTD determined in Group A cohort.
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Accelerate Brain Cancer Cure, Lyla Nsouli Foundation
- Responsible party
- Sponsor
- Investigators
- Elias Sayour, MD, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03396575
- Sponsor's protocol ID
- IRB201701296
- Other IDs
- OCR16024
- Acronym
- BRAVO
- Status last verified
- Oct 2025
- First submitted
- 4 Jan 2018
- Last updated
- 29 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BRAVO: Newly-Diagnosed Brain Stem Gliomas Treated With Adoptive Cellular Therapy During Recovery From Focal Radiotherapy Alone or Focal Radiotherapy and Dose-intensified Temozolomide (Phase I)
- ClinicalTrials.gov ID
- NCT03396575
- Acronym / sponsor ID
- BRAVO / IRB201701296
- Keywords
- Tumor mRNA-pulsed autologous Dendritic Cells (TTRNA-DCs), Tumor-specific autologous lymphocyte transfer (TTRNA-xALT), Autologous G-CSF mobilized HSCs, Temozolomide (TMZ), Cyclophosphamide (CTX), Fludarabine (Flu), Immunotherapy, Pediatric
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not feasible to accrue due to competing studies
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Accelerate Brain Cancer Cure, Lyla Nsouli Foundation
- Study start
- 17 Jul 2018 (actual)
- Primary completion
- 20 Mar 2025 (actual)
- Study completion
- 20 Mar 2025 (actual)
- First posted
- 11 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The standard of care for children with DIPG includes focal radiotherapy (RT) but outcomes have remained dismal despite this treatment. The addition of oral Temozolomide (TMZ) concurrently with RT followed by monthly TMZ was also found to be safe but ineffective. Recent studies in adults have shown that certain types of chemotherapy induce a profound but transient lymphopenia (low blood lymphocytes) and vaccinating and/or the adoptive transfer of tumor-specific lymphocytes into the cancer patient during this lymphopenic state leads to dramatic T cell expansion and potent immunologic and clinical responses. Therefore, patients in this study will either receive concurrent TMZ during RT and immunotherapy during and after maintenance cycles of dose-intensive TMZ (Group A) or focal radiotherapy alone and immunotherapy without maintenance DI TMZ (Group B). Immune responses during cycles of DC vaccination with or without DI TMZ will be evaluated in both treatment groups.
Detailed description
The standard of care for children with DIPG includes external beam focal radiotherapy (RT) but outcomes have remained dismal despite this treatment. The addition of oral Temozolomide (TMZ) concurrently with focal irradiation followed by maintenance monthly TMZ was also found to be safe but ineffective. However, in the context of an immunotherapy strategy, it might be beneficial to use TMZ as an adjuvant therapy during and following radiotherapy. Recent pre-clinical and clinical studies in adults with have shown that both myeloablative (MA) and non-myeloablative (NMA) chemotherapy induce a profound but transient lymphopenia and, somewhat counterintuitively, vaccination during recovery from this lymphopenic state and/or the adoptive transfer of tumor-specific lymphocytes into lymphodepleted hosts leads to dramatic in vivo T cell expansion and potent immunologic and clinical responses. Therefore, the study team expects that tumor-specific lymphocytes, expanded ex vivo with the use of TTRNA-pulsed DCs may provide a source of lymphocytes that preferentially expand in this lymphopenic environment following TMZ, and serve as a source of responder cells to subsequent DC vaccination.
TMZ induces profound lymphopenia in children with central nervous system (CNS) tumors. It has not been conclusively shown to help in augmenting vaccine-induced immune responses in this population. Patients in this study will either receive concurrent TMZ during RT and immunotherapy during and after maintenance cycles of dose-intensive TMZ (Group A) or focal radiotherapy alone and immunotherapy without maintenance DI TMZ (Group B). Immune responses during cycles of DC vaccination with or without DI TMZ will be evaluated in both treatment groups. The immunotherapy regimen will consist of TTRNA-DC vaccines alone followed by adoptive cellular therapy consisting of ex vivo expanded tumor-reactive lymphocytes coupled with TTRNA-DC vaccines and autologous HSCs.
Patients in Group B will not receive DI TMZ, however, they will receive lymphodepletion with cyclophosphamide + fludarabine after DC vaccination and prior to the intravenous infusion of ex vivo expanded tumor-reactive lymphocytes. T cell engraftment and persistence has been shown to be augmented by lymphodepletion in numerous studies. TTRNA-pulsed DCs will be given in conjunction with the adjuvants GM-CSF and tetanus-diphtheria toxoid (Td) vaccine which the study team have shown can significantly enhance clinical responses to DC vaccination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients in this study will either receive concurrent TMZ during RT and dose-intensive TMZ as maintenance treatment (Group A) or radiotherapy only prior to DC vaccination and without maintenance DI TMZ (Group B). Immune responses during cycles of DC vaccination with or without DI TMZ will be evaluated in both treatment groups. Once Group A accrual is completed and evaluated for toxicity, 6 Group B patients will be enrolled and treated at the Maximally Achievable Dose (MAD) or (Maximum Tolerated Dose) MTD determined in Group A cohort.
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Biological: TTRNA-DC vaccines with GM-CSF, Biological: TTRNA-xALT, Drug: Dose-Intensified TMZ, Drug: Td vaccine, Biological: Autologous Hematopoietic Stem Cells (HSC)TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) during cycles of Dose-intensified TMZ |
| Group B | Experimental | Biological: TTRNA-DC vaccines with GM-CSF, Biological: TTRNA-xALT, Drug: Cyclophosphamide + Fludarabine Lymphodepletive Conditioning, Drug: Td vaccine, Biological: Autologous Hematopoietic Stem Cells (HSC)TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) with Cyclophosphamide + Fludarabine Lymphodepletive Conditioning |
Who may qualify
- Ages
- 3 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Initial Screening
- Radiologically confirmed DIPG or other diffuse intrinsic brain stem glioma (Grade III or IV).
- Patient and/or parents/guardian willing to consent to biopsy for obtaining tumor material for confirmatory diagnosis and/or tumor RNA extraction and amplification.
- Biopsy confirmation of any grade of glioma (for patients with classic DIPG on neuroimaging or at least grade III glioma in case of other diffuse intrinsic brain stem gliomas)
- Karnofsky Performance Status (KPS) of > 50% (KPS for > 16 years of age) or Lansky performance Score (LPS) of ≥ 50 (LPS for ≤ 16 years of age) assessed within 2 weeks prior to registration;
Key exclusion criteria (11 listed)
- Patients with severe dysphagia, obtundation, or tetraplegia (poor risks for anesthesia and biopsy procedure);
- Absence of tumor on biopsy specimen;
- 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;
- Patients with significant renal, cardiac, pulmonary, hepatic or other organ dysfunction;
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 |
| TTRNA-xALTDuring TMZ Cycle 4 and with DC vaccine #6, an infusion of T-cells will be administered to all subjects. | Biological | Group A, Group B |
| Cyclophosphamide + Fludarabine Lymphodepletive ConditioningSubjects in Group B, however, will receive lymphodepletion with cyclophosphamide + fludarabine after DC vaccination and prior to the intravenous infusion of ex vivo expanded tumor-reactive lymphocytes. | Drug | Group B |
| Dose-Intensified TMZAfter chemoradiation, subjects in Group A 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 |
| 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 |
| Autologous Hematopoietic Stem Cells (HSC)During Cycle 4, all patients will receive HSCs prior to xALT infusion and DC vaccine #6. | Biological | Group A, Group B |
Primary outcome
Feasibility and safety of adoptive cellular therapy in pediatric patients with DIPG with or without dose-intensified TMZ during cycles of DC vaccination
Time frame: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death
Number of subjects with immunotherapy-related dose-limiting toxicities including 1) Grade III or greater non-neurologic toxicity; 2) Grade III neurologic toxicity that does not improve to Grade II or better within 5 days; or 3) Grade IV neurologic toxicity.
Determine the maximally achievable dose (MAD) or maximum tolerated dose (MTD) of xALT plus DC and HSC in Group A and Group B subjects
Time frame: From first DC vaccine in Group A until 14 days after administration of the last dose of investigational product is given.
The first 6 patients in Group A (receiving DI TMZ) at a dose of 3 x 107 cells /kg xALT and if dose-limiting toxicities are observed in no more than 1 of 6 patients, the study team will enroll another 6 patients at the next dose level of 3 x108 cells /kg. If no more than 1 patient suffers dose limiting toxicity (DLT) at this dose level, it will declared the MAD of T cells. Subjects enrolled in Group B will be treated at the MAD or MTD determined in the Group A Cohort.
3 secondary outcomes
Post-immunotherapy functional anti-tumor immune responses
Time frame: Up to 10 months
Analysis of progression-free survival (PFS)
Time frame: Up to 5 years
Analysis of overall survival (OS)
Time frame: Up to 5 years
Results and safety
The study was stopped early (reason given: Not feasible to accrue due to competing studies). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2025.
Related trials for Diffuse Intrinsic Pontine Glioma (DIPG)
RecruitingObservational study
International Diffuse Intrinsic Pontine Glioma (DIPG)/Diffuse Midline Glioma (DMG) Registry and Repository
Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant
RecruitingPhase 2
ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas
Diffuse Intrinsic Pontine Gliomas (DIPG), Progressive DIPG
RecruitingPhase 3
Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0
Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant
RecruitingPhase 2
Illuminate: A Clinical Study Evaluating CAR T Immune Cell Therapy (BCB-276) for Patients With Diffuse Intrinsic Pontine Glioma (DIPG).
Diffuse Intrinsic Pontine Glioma, DIPG
Not yet recruitingPhase 2
Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)
High Grade Glioma (HGG) of the Brain With BRAF Aberration, High Grade Glioma (III or IV)
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
1 site 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, TTRNA-xALT and Cyclophosphamide + Fludarabine Lymphodepletive Conditioning in people with Diffuse Intrinsic Pontine Glioma (DIPG) and Brain Stem Glioma, run by University of Florida at 1 site 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 20 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: stopped early, as of the sponsor's last update on 29 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study was stopped early (reason given: Not feasible to accrue due to competing studies). Results are not available in the source record.
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?
Feasibility and safety of adoptive cellular therapy in pediatric patients with DIPG with or without dose-intensified TMZ during cycles of DC vaccination (time frame: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death). The study lists 2 primary outcomes in all. 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 29 Oct 2025.