Recurrent Diffuse Hemispheric Glioma, H3 G34-MutantPhase 1NCT06914479
Virus-Based Gene Therapy (AdV-HSV1-TK and AdV-Flt3L) in Combination With Valacyclovir for the Treatment of Pediatric and Young Adult Patients With Resectable, Recurrent Primary Malignant Brain Tumors
A Phase 1 study testing Ad-hCMV-Flt3L, Ad-hCMV-TK and Biospecimen Collection in people with Recurrent Diffuse Hemispheric Glioma, H3 G34-Mutant and Recurrent Malignant Brain Neoplasm, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
This phase I trial tests the safety, side effects and best dose of AdV-HSV1-TK and AdV-Flt3L in combination with valacyclovir for the treatment of patients with primary cancerous (malignant) brain tumors that can be removed by surgery (resectable) and that have come back after a period of improvement (recurrent). Read more about this study
- Who is it for?
- Ages 3 to 39 years
- Conditions the study is for
- Recurrent Diffuse Hemispheric Glioma, H3 G34-Mutant, Recurrent Malignant Brain Neoplasm, Resectable Brain Neoplasm
- What is being tested?
- Ad-hCMV-Flt3L, Ad-hCMV-TK and Biospecimen Collection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 22 May 2026to May 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 3 to 25 years with:
- Diagnosis of malignant primary brain tumor after tumor recurrence, relapse, or progression who have completed up-front, standard-of-care therapy
- Age 26 to 39 years with:
- Diagnosis of diffuse hemispheric glioma, H3 G34-mutant, per 2021 World Health Organization (WHO) classification, after tumor recurrence, relapse, or progression who have completed up-front, standard-of-care therapy
- At least 10 kg (and body surface area [BSA] > 0.5 m^2)
- Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 3 days prior to baseline MRI
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- Surgical resection of the tumor recurrence/relapse/progression is clinically indicated at the time of enrollment
- A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate
- Participant must be willing to provide archival formalin-fixed embedded (FFPE) and/or frozen tissue specimens, if available
- Participant must have recovered from all acute side effects of prior therapy.
- From the projected start of scheduled study treatment, the following time periods must have elapsed: At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibody therapy (21 days for bevacizumab,.6 weeks from cellular therapy (i.e. modified T cells, natural killer [NK] cells, dendritic cells, etc.), or 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies
- For participants who have received radiotherapy previously, participants must be at least 28 days from focal radiation therapy, at least 150 days from craniospinal irradiation therapy.
- The use of bevacizumab to control radiation therapy-induced edema is allowed prior to or during study therapy (if used for tumor-directed therapy, please see required washout period above).
- Dosing limitations are as follows:
- Bevacizumab (or bioequivalent) for up to a maximum of 5 doses, dosing per institutional standard. There is no required washout period
- Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg/m^2/dose continuously during radiation therapy) or dexamethasone is allowed
- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm^3 (1.0g/l)
- Platelet count ≥ 100,000/mm^3 (100x10^9/l) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70mL/min/1.73 m^2 or a serum creatinine within the normal limits for age
- Bilirubin (sum of conjugated + unconjugated) ≤ 2 x upper limit of normal (ULN) for age
- Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x ULN
- Serum albumin ≥ 2 g/dL
- Performance score ≥ 60 (Karnofsky for participants > 16 years of age, Lansky for participants ≤ 16 years of age.)
- Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- The effects of the study drugs on the developing human fetus are unknown. For this reason, females of child-bearing potential (FOCBP) and males must agree to use adequate contraception for the duration of study participation and 30 days after last dose of AdV-HSV1-TK/AdV-Flt3L or valacyclovir, whichever is later.
- Adequate methods include hormonal or barrier method of birth control, or abstinence at the time of study entry and for the duration of study participation.
- Should a participant become pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately.
- Males treated on this study must also agree to use adequate contraception as of the time of enrollment onto the study and for the duration of study participation. Male participants must notify the treating physician immediately if his partner becomes pregnant while he is receiving study therapy
Who cannot join
- Patient deemed not clinically appropriate to undergo tumor tissue resection by a neurosurgeon
- Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of cerebrospinal fluid (CSF) dissemination
- Patient with primary brainstem or primary spinal tumors
- History of prior gene therapy
- Ongoing therapy with valacyclovir that is unable to be stopped due to a medical condition
- Known allergy to valacyclovir
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- Concurrent use of other investigational agents.
- Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy/resection should be discussed with the study chairs
- Participants who are currently receiving anti-cancer agents
- Participants with a known disorder that affects their immune system, such as HIV or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy
- Presence of uncontrolled infection or other uncontrolled systemic illness
- Current diagnosis of bipolar disorder or major depressive disorder
- Presence of a congenital immune deficiency syndrome or acquired autoimmune disease
- Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine or serum pregnancy test prior to the start of therapy (as clinically indicated)
- Active illicit drug use or diagnosis of alcoholism
- History of kidney transplant
- History of allogeneic stem cell transplantation
- Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Andrea T. Franson, 800-865-1125, CancerAnswerLine@med.umich.edu
Andrea T. Franson
About this study
Official title: A Phase 1 Study of a Combined Cytotoxic and Immune-Stimulatory Therapy in Pediatric and Young Adult Patients With Recurrent, Primary Malignant Brain Tumors
This phase I trial tests the safety, side effects and best dose of AdV-HSV1-TK and AdV-Flt3L in combination with valacyclovir for the treatment of patients with primary cancerous (malignant) brain tumors that can be removed by surgery (resectable) and that have come back after a period of improvement (recurrent). AdV-HSV1-TK and AdV-Flt3L use a virus modified in the laboratory to kill tumor cells and stimulate the immune system to recognize the tumor cells as "invaders" which can lead to tumor shrinkage. For this process to work, an oral anti-herpes medication called valacyclovir is also needed. Giving AdV-HSV1-TK, AdV-Flt3L and valacyclovir may be safe, tolerable and/or effective in treating patients with resectable, recurrent primary malignant brain tumors.
Read the detailed description
22MAY2026- Inclusion criteria updated to correct a typographical error regarding serum albumin.
- Conditions
- Recurrent Diffuse Hemispheric Glioma, H3 G34-Mutant, Recurrent Malignant Brain Neoplasm, Resectable Brain Neoplasm
- Being tested
- Ad-hCMV-Flt3L, Ad-hCMV-TK, Biospecimen Collection, Magnetic Resonance Imaging, Survey Administration
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad-hCMV-Flt3LGenetic
Given via injection
Ad-hCMV-TKGenetic
Given via injection
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Survey AdministrationOther
Ancillary studies
Tumor ResectionProcedure or surgery
Undergo standard of care tumor resection
ValacyclovirDrug
Also called Valaciclovir, ValACV, Zelitrex
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) | Experimental | Patients undergo standard of care tumor resection and receive AdV-HSV1-TK and AdV-Flt3L via multiple injections over 3-5 minutes each to areas around the tumor. One to three days after surgery, patients receive valacyclovir PO TID on days 1-14 of each cycle. Cycles repeat every 12 weeks for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive standard of care radiation therapy starting on day 21. Patients undergo MRI and blood sample collection throughout the study. Receives: Genetic: Ad-hCMV-Flt3L; Genetic: Ad-hCMV-TK; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Survey Administration; Procedure: Tumor Resection; Drug: Valacyclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT)
Each participant will be classified as either having a DLT prior to Day 21 after dual vector administration or Day 21 after dual vector administration with no DLT (a binary endpoint). Adverse events (AEs) will be defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.
Measured: Up to day 21
Secondary outcomes (4)
Overall survival at 6 months (OS6)
Defined as the percentage of participants alive at least 6 months (26 weeks) after the study enrollment. Will be addressed by using the Kaplan-Meier method with confidence intervals. Estimation of OS6 will be addressed by using the Kaplan-Meier method with confidence intervals (R module: 'survival').
Measured: At 6 months
OS time
Estimation of median OS will be addressed by using the Kaplan-Meier method with confidence intervals (R module: 'survival').
Measured: From study enrollment until death from any cause, up to 5 years
Progression free survival at 6 months (PFS6)
Defined as the percentage of participants alive and free from progression (relapse, progression per Response Assessment in Pediatric Neuro-Oncology [RAPNO] criteria, or death from any cause) at 6 months (26 weeks) after study enrollment. Estimation of PFS6 will be addressed by using the Kaplan-Meier method with confidence intervals (R module: 'survival'). Point estimates of PFS6 will be presented along with either standard error or 90% confidence intervals.
Measured: At 6 months after study enrollment
PFS time
Estimation of median PFS will be addressed by using the Kaplan-Meier method with confidence intervals (R module: 'survival').
Measured: From study enrollment until the occurrence of the first event (relapse, progression per RAPNO criteria, or death from any cause), 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 posted6 Apr 2025
- Study start22 May 2026
- Primary completionMay 2031 (estimated)
- Study completionMay 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Diffuse Hemispheric Glioma, H3 G34-MutantStudies 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
- 11 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrea T Franson, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06914479
- Sponsor's protocol ID
- UMCC 2024.064
- Other IDs
- NCI-2025-01951, HUM00252291
- Status last verified
- Jun 2026
- First submitted
- 31 Mar 2025
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of a Combined Cytotoxic and Immune-Stimulatory Therapy in Pediatric and Young Adult Patients With Recurrent, Primary Malignant Brain Tumors
- ClinicalTrials.gov ID
- NCT06914479
- Acronym / sponsor ID
- UMCC 2024.064
- Conditions
- Recurrent Diffuse Hemispheric Glioma, H3 G34-Mutant, Recurrent Malignant Brain Neoplasm, Resectable Brain Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 11 participants (estimated)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- 22 May 2026 (actual)
- Primary completion
- May 2031 (estimated)
- Study completion
- May 2031 (estimated)
- First posted
- 6 Apr 2025 (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.
This phase I trial tests the safety, side effects and best dose of AdV-HSV1-TK and AdV-Flt3L in combination with valacyclovir for the treatment of patients with primary cancerous (malignant) brain tumors that can be removed by surgery (resectable) and that have come back after a period of improvement (recurrent). AdV-HSV1-TK and AdV-Flt3L use a virus modified in the laboratory to kill tumor cells and stimulate the immune system to recognize the tumor cells as "invaders" which can lead to tumor shrinkage. For this process to work, an oral anti-herpes medication called valacyclovir is also needed. Giving AdV-HSV1-TK, AdV-Flt3L and valacyclovir may be safe, tolerable and/or effective in treating patients with resectable, recurrent primary malignant brain tumors.
Detailed description
22MAY2026- Inclusion criteria updated to correct a typographical error regarding serum albumin.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) | Experimental | Genetic: Ad-hCMV-Flt3L, Genetic: Ad-hCMV-TK, Procedure: Biospecimen Collection, Procedure: Magnetic Resonance Imaging, Other: Survey Administration, Procedure: Tumor Resection, Drug: ValacyclovirPatients undergo standard of care tumor resection and receive AdV-HSV1-TK and AdV-Flt3L via multiple injections over 3-5 minutes each to areas around the tumor. One to three days after surgery, patients receive valacyclovir PO TID on days 1-14 of each cycle. Cycles repeat every 12 weeks for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive standard of care radiation therapy starting on day 21. Patients undergo MRI and blood sample collection throughout the study. |
Who may qualify
- Ages
- 3 to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Age 3 to 25 years with:
- Age 26 to 39 years with:
- At least 10 kg (and body surface area [BSA] > 0.5 m^2)
- Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 3 days prior to baseline MRI
- Surgical resection of the tumor recurrence/relapse/progression is clinically indicated at the time of enrollment
Key exclusion criteria (18 listed)
- Patient deemed not clinically appropriate to undergo tumor tissue resection by a neurosurgeon
- Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of cerebrospinal fluid (CSF) dissemination
- Patient with primary brainstem or primary spinal tumors
- History of prior gene therapy
- Ongoing therapy with valacyclovir that is unable to be stopped due to a medical condition
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-hCMV-Flt3LGiven via injection | Genetic | Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) |
| Ad-hCMV-TKGiven via injection | Genetic | Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) |
| Survey AdministrationAncillary studies | Other | Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) |
| Tumor ResectionUndergo standard of care tumor resection | Procedure or surgery | Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) |
| ValacyclovirAlso: Valaciclovir, ValACV, ZelitrexGiven PO | Drug | Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) |
Primary outcome
Dose limiting toxicity (DLT)
Time frame: Up to day 21
Each participant will be classified as either having a DLT prior to Day 21 after dual vector administration or Day 21 after dual vector administration with no DLT (a binary endpoint). Adverse events (AEs) will be defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.
4 secondary outcomes
Overall survival at 6 months (OS6)
Time frame: At 6 months
OS time
Time frame: From study enrollment until death from any cause, up to 5 years
Progression free survival at 6 months (PFS6)
Time frame: At 6 months after study enrollment
PFS time
Time frame: From study enrollment until the occurrence of the first event (relapse, progression per RAPNO criteria, or death from any cause), up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Individual participant dataSharing planned: Undecided
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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.
Andrea T Franson principal investigator
University of Michigan Rogel Cancer Center
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 Ad-hCMV-Flt3L, Ad-hCMV-TK and Biospecimen Collection in people with Recurrent Diffuse Hemispheric Glioma, H3 G34-Mutant and Recurrent Malignant Brain Neoplasm, run by University of Michigan Rogel Cancer Center 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 28 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 15 Jun 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cancer AnswerLine (1-800-865-1125, CancerAnswerLine@med.umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (DLT) (time frame: Up to day 21). 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 15 Jun 2026; AzTrials last refreshed its copy on 26 Oct 2026.