Recurrent High Grade GliomaPhase 1PuMPNCT06126744
Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of the Oncolytic HSV1 MVR-C5252
A Phase 1 study testing MVR-C5252 in people with Recurrent High Grade Glioma, run by Duke University at 2 sites in United States.
Trial summary
This is a Phase 1 open label study designed to assess the safety and tolerability of the oncolytic herpes simplex virus 1 (oHSV1) study drug, MVR-C5252, administered intratumorally by convection-enhanced delivery (CED) in patients with recurrent high-grade glioma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent High Grade Glioma
- What is being tested?
- MVR-C5252
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Jun 2024to 1 Dec 2028
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years of age
- Disease recurrence of at least 1x1cm and a maximum of 3x3cm of enhancing tumor:
- Dose escalation portion: patients with recurrent high-grade glioma, IDH wt or IDH mutated, grade 3 or grade 4 based on imaging.
- Dose expansion portion: Recurrent, IDH wt, glioblastoma, WHO grade 4. Diagnosis has be made using the 2021 WHO Classification of Tumors of the CNS.
- The neurosurgeon must confirm (a) the tumor location (> 1 cm from eloquent brain), (b) that the placement of infusion catheter within or through the progressive enhancing tumor is feasible and is at a safe distance to eloquent brain function. These aspects will be determined prior catheter placement on the basis of prior (screening) MRI and then at the time of catheter placement on the basis of a CT scan prior to infusion. The tip of the catheter must be placed as follows:
- Within the enhancing portion or in the vicinity of enhancement of target lesion (i.e., infiltrative disease)
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- ≥ 0.5 cm from ventricles
- ≥ 1 cm deep into the brain
- ≥ 0.5 cm from the corpus callosum
- If a histological or pathological confirmation of recurrence (< 6 weeks) is not available, a pre-infusion biopsy will be required to confirm recurrence.
- Adequate pulmonary function, with a baseline pulse oximetry of at 90% on room air.
- The subject must have received standard radiation therapy plus temozolomide and be refractory to radiation therapy plus temozolomide prior to enrollment.
- Prior to administration of MVR-C5252, the presence of recurrent tumor must be confirmed by histopathological analysis. (Distinguishing between recurrent active tumor and radiation necrosis is important to avoid delivering MVR-C5252 when there is no active disease).
- Should participants have further surgical resection at any time following their participation in the study, patients will be invited to make any biospecimens available for correlative research.
- Karnofsky Performance Status (KPS) ≥ 70%
- Labs:
- platelets ≥ 100,000 unsupported at initial screening, but ≥ 125,000 supported prior to biopsy/catheter insertion
- hemoglobin ≥ 9 gm/dL, ANC ≥ 1000/µL
- creatinine ≤ 1.5x upper limit of normal (ULN)
- total bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 2.5 x ULN (subjects with known or suspected Gilbert's syndrome are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN)
- PT, aPTT ≤ 1.2 x ULN prior to biopsy (if patient is taking warfarin, INR should be obtained and be < 2.0)
- Able to undergo MRI brain with and without contrast
- If the patient is a sexually active female of childbearing potential, whose partner is male, or if the patient is a sexually active male, whose partner is a female of child bearing potential, the patient must use appropriate contraceptive measures for the duration of the treatment and for 6 months afterwards. Female patients of childbearing potential must have a negative serum pregnancy test at the time of screening and within 48 hours of starting the MVR-C5252 infusion.
- Signed informed consent approved by the Institutional Review Board
Who cannot join
- Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
- Patients who are pregnant or breastfeeding
- Patients with contrast-enhancing tumor crossing the midline, multifocal tumor, infratentorial tumor, tumor in eloquent brain regions, extensive tumor dissemination (subependymal or leptomeningeal), or in unsafe brain regions per the opinion of the treating neurosurgeon
- Unstable systemic disease in the opinion of the treating physician.
- Active infection requiring systemic therapy or causing fever (temperature > 38.1˚C) or subjects with unexplained fever (temperature > 38.1˚C) within 7 days prior to the day of investigational product administration.
- Patients on >4 mg per day of dexamethasone within the 2 weeks prior to admission for MVR-C5252 infusion or systemic therapy with immunosuppressive agents within 28 days prior to admission for MVR-C5252 infusion
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- Patients who have not completed standard of care treatment prior to participation in this trial
- Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation of recurrent tumor
- Treated with immunotherapeutic agents prior to MVR-C5252 treatment, within 4 weeks, alkylating agents within 4 weeks, nitrosoureas within 6 weeks, or non-alkylating chemotherapy within 2 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy
- Treated with antiangiogenic agents (i.e., bevacizumab) within 4 weeks before biopsy
- Patients who require an attenuated or live vaccine within 28 days prior to the first trial drug administration and during the study treatment period
- Prior treatment with any oncolytic virus, cell therapy or gene therapy.
- Prior antitumor treatment with intracranial implants, such as Carmustine
- Previous history of allergic reactions to similar biological components such as HSV-1, IL-12 or anti-PD-1 antibodies, or with known allergic reactions to any component of the MVR-C5252 prescription, including glycerol.
- Systemic use (other than topical) of anti-HSV drugs (including, but not limited to, acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir, etc.)
- Patients with cardiac risks including congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry, or a history of myocarditis.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Duke University
Durham, North Carolina, 27750
Mustafa Khasraw, MD, 919-681-8838, mustafa.khasraw@duke.edu
BTC Triage Help, 919-684-5301, dukebrain1@duke.edu
- Recruiting
Memorial Sloan Kettering
New York, New York, 10065
Christian Grommes, MD, 212-610-0344, grommesc@mskcc.org
Lauren Schaff, MD, 212-610-0485, schaffl@mskcc.org
About this study
Official title: The PuMP Trial: "A Multistage Phase 1 Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of the Oncolytic HSV1 MVR-C5252 in Patients With Recurrent High-Grade Glioma"
This is a Phase 1 open label study designed to assess the safety and tolerability of the oncolytic herpes simplex virus 1 (oHSV1) study drug, MVR-C5252, administered intratumorally by convection-enhanced delivery (CED) in patients with recurrent high-grade glioma. Once the safety and maximum tolerated dose (MTD) is established in the dose escalation portion of the trial, a dose expansion cohort at the recommended phase 2 dose (RP2D) in patients with isocitrate dehydrogenase (IDH) wildtype recurrent glioblastoma (GBM) will evaluate preliminary efficacy of the study drug.
Read the detailed description
Oncolytic HSV1 (oHSV1) was the first viral vector studied in clinical trials to treat malignant glioma with positive outcomes for tolerability and potential clinical benefits. MVR-C5252 is a genetically modified next generation oHSV1 with an active domain of human IL-12 and Fab fragment of anti-PD-1 antibody. During viral replication, IL-12 and anti-PD-1 antibody are expressed and secreted into the tumor microenvironment, acting synergistically by increasing the T cell infiltration, converting the cold (immune suppressing) tumor to hot (immune active) tumor, and inducing anti-tumor specific immunity. This study is investigating if oHSV1 MVR-C5252 administered via CED can overcome the BBB (Blood Brain Barrier) in patients with recurrent high-grade glioma. This study will enroll patients in 4 Stages. In Stage 1, externalized Synchromed II pump will be used to deliver Gadoliunium followed by MVR-C5252 for a single administration on Day 1. Stage 2, two infusions will be administered-on days 1 and 28 via the internalized pump. For patients accrued on Stage 3, the second infusion of study drug (Cycle 1, infusion 2) will occur 7 ± 1 days after 1st infusion for a total of 6 cycles (12 infusions). Stage 4, the dose expansion portion of the study, will commence once a MTD/RP2D is established. Within Stage 4 the efficacy of the study drug, as measured by progression-free 6 months survival will be evaluated.
- Conditions
- Recurrent High Grade Glioma
- Being tested
- MVR-C5252
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MVR-C5252Biological
MVR-C5252 is a genetically modified next generation oncolytic herpes simplex virus 1 (oHSV1) with an active domain of human IL-12 and Fab fragment of anti-PD-1 antibody. This is a Phase 1 open label study designed to determine the safety and tolerability of MVR-C5252. The dose-escalation portion of the study will be conducted in 4 stages to evaluate the safety of infusion and determination of the MTD/RP2D followed by efficacy assessment.
| Study group | Role | What they receive |
|---|---|---|
| MVR-C5252 | Experimental | Open label single arm infusion of MVR-C5252, genetically engineered type 1 oHSV (oncolytic herpes simplex viruses) into the tumor via Convection-enhanced delivery (CED) a modality that can bypass the BBB (Blood Brain Barrier), allowing the intracranial delivery through the BBB and avoiding systemic toxicities. Receives: Biological: MVR-C5252 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1: Proportion of patients with dose-limiting toxicity (DLT) during the single infusion
Proportion of patients with dose-limiting toxicity (DLT) during the single infusion
Measured: Day 1 of treatment until 28 days post first infusion
Stage 2: Proportion of patients with dose-limiting toxicity (DLT) during 2 infusions using the internalized Ascenda catheter
Proportion of patients with DLT who have received two infusions on days 1 and 28
Measured: Day 1 of treatment until 28 days post second infusion for a total of up to 56 days post first infusion
Stage 3a: Proportion of patients with dose-limiting toxicity (DLT) after each cycle with two infusions on days 1 and 8
Proportion of patients with DLT who have received two infusions on days 1 and 8
Measured: Day 1 of treatment until 28 days post second infusion for a total of up to 35 days post first infusion
Stage 3b: Determine the MTD/RP2D
Maximal Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)
Measured: Day 1 of treatment until 28 days post second infusion for a total of up to 35 days post first infusion for all the cycles for all the patients enrolled in stages 1, 2 and 3
Stage 4: Progression Free Survival at 6 months
Progression Free Survival at 6 months will be estimated by the Kaplan-Meier method
Measured: Day 1 of treatment until first documentation of disease progression or date of death, whichever comes first, assessed up to 6 months
Secondary outcomes (2)
Overall Survival
Day 1 of treatment until death to calculate Median overall survival by the Kaplan-Meier method.
Measured: 5 years
Progression Free Survival
Day 1 of treatment until first documentation of disease progression or death to calculate Median progression free survival by the Kaplan-Meier method.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start11 Jun 2024
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent High Grade GliomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mustafa Khasraw, MBChB, MD, FRCP, FRACP, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06126744
- Sponsor's protocol ID
- Pro00112883
- Acronym
- PuMP
- Status last verified
- Apr 2026
- First submitted
- 24 Sep 2023
- Last updated
- 15 Apr 2026
- Results posted
- No
- 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 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The PuMP Trial: "A Multistage Phase 1 Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of the Oncolytic HSV1 MVR-C5252 in Patients With Recurrent High-Grade Glioma"
- ClinicalTrials.gov ID
- NCT06126744
- Acronym / sponsor ID
- PuMP / Pro00112883
- Conditions
- Recurrent High Grade Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 11 Jun 2024 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 13 Nov 2023 (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 is a Phase 1 open label study designed to assess the safety and tolerability of the oncolytic herpes simplex virus 1 (oHSV1) study drug, MVR-C5252, administered intratumorally by convection-enhanced delivery (CED) in patients with recurrent high-grade glioma. Once the safety and maximum tolerated dose (MTD) is established in the dose escalation portion of the trial, a dose expansion cohort at the recommended phase 2 dose (RP2D) in patients with isocitrate dehydrogenase (IDH) wildtype recurrent glioblastoma (GBM) will evaluate preliminary efficacy of the study drug.
Detailed description
Oncolytic HSV1 (oHSV1) was the first viral vector studied in clinical trials to treat malignant glioma with positive outcomes for tolerability and potential clinical benefits. MVR-C5252 is a genetically modified next generation oHSV1 with an active domain of human IL-12 and Fab fragment of anti-PD-1 antibody. During viral replication, IL-12 and anti-PD-1 antibody are expressed and secreted into the tumor microenvironment, acting synergistically by increasing the T cell infiltration, converting the cold (immune suppressing) tumor to hot (immune active) tumor, and inducing anti-tumor specific immunity. This study is investigating if oHSV1 MVR-C5252 administered via CED can overcome the BBB (Blood Brain Barrier) in patients with recurrent high-grade glioma. This study will enroll patients in 4 Stages. In Stage 1, externalized Synchromed II pump will be used to deliver Gadoliunium followed by MVR-C5252 for a single administration on Day 1. Stage 2, two infusions will be administered-on days 1 and 28 via the internalized pump. For patients accrued on Stage 3, the second infusion of study drug (Cycle 1, infusion 2) will occur 7 ± 1 days after 1st infusion for a total of 6 cycles (12 infusions). Stage 4, the dose expansion portion of the study, will commence once a MTD/RP2D is established. Within Stage 4 the efficacy of the study drug, as measured by progression-free 6 months survival will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MVR-C5252 | Experimental | Biological: MVR-C5252Open label single arm infusion of MVR-C5252, genetically engineered type 1 oHSV (oncolytic herpes simplex viruses) into the tumor via Convection-enhanced delivery (CED) a modality that can bypass the BBB (Blood Brain Barrier), allowing the intracranial delivery through the BBB and avoiding systemic toxicities. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Age >18 years of age
- Disease recurrence of at least 1x1cm and a maximum of 3x3cm of enhancing tumor:
- Dose escalation portion: patients with recurrent high-grade glioma, IDH wt or IDH mutated, grade 3 or grade 4 based on imaging.
- Dose expansion portion: Recurrent, IDH wt, glioblastoma, WHO grade 4. Diagnosis has be made using the 2021 WHO Classification of Tumors of the CNS.
- The neurosurgeon must confirm (a) the tumor location (> 1 cm from eloquent brain), (b) that the placement of infusion catheter within or through the progressive enhancing tumor is feasible and is at a safe distance to eloquent brain function. These aspects will be determined prior catheter placement on the basis of prior (screening) MRI and then at the time of catheter placement on the basis of a CT scan prior to infusion. The tip of the catheter must be placed as follows:
Key exclusion criteria (16 listed)
- Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
- Patients who are pregnant or breastfeeding
- Patients with contrast-enhancing tumor crossing the midline, multifocal tumor, infratentorial tumor, tumor in eloquent brain regions, extensive tumor dissemination (subependymal or leptomeningeal), or in unsafe brain regions per the opinion of the treating neurosurgeon
- Unstable systemic disease in the opinion of the treating physician.
- Active infection requiring systemic therapy or causing fever (temperature > 38.1˚C) or subjects with unexplained fever (temperature > 38.1˚C) within 7 days prior to the day of investigational product administration.
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 |
|---|---|---|
| MVR-C5252MVR-C5252 is a genetically modified next generation oncolytic herpes simplex virus 1 (oHSV1) with an active domain of human IL-12 and Fab fragment of anti-PD-1 antibody. This is a Phase 1 open label study designed to determine the safety and tolerability of MVR-C5252. The dose-escalation portion of the study will be conducted in 4 stages to evaluate the safety of infusion and determination of the MTD/RP2D followed by efficacy assessment. | Biological | MVR-C5252 |
Primary outcome
Stage 1: Proportion of patients with dose-limiting toxicity (DLT) during the single infusion
Time frame: Day 1 of treatment until 28 days post first infusion
Proportion of patients with dose-limiting toxicity (DLT) during the single infusion
Stage 2: Proportion of patients with dose-limiting toxicity (DLT) during 2 infusions using the internalized Ascenda catheter
Time frame: Day 1 of treatment until 28 days post second infusion for a total of up to 56 days post first infusion
Proportion of patients with DLT who have received two infusions on days 1 and 28
Stage 3a: Proportion of patients with dose-limiting toxicity (DLT) after each cycle with two infusions on days 1 and 8
Time frame: Day 1 of treatment until 28 days post second infusion for a total of up to 35 days post first infusion
Proportion of patients with DLT who have received two infusions on days 1 and 8
Stage 3b: Determine the MTD/RP2D
Time frame: Day 1 of treatment until 28 days post second infusion for a total of up to 35 days post first infusion for all the cycles for all the patients enrolled in stages 1, 2 and 3
Maximal Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)
Stage 4: Progression Free Survival at 6 months
Time frame: Day 1 of treatment until first documentation of disease progression or date of death, whichever comes first, assessed up to 6 months
Progression Free Survival at 6 months will be estimated by the Kaplan-Meier method
2 secondary outcomes
Overall Survival
Time frame: 5 years
Progression Free Survival
Time frame: 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 Apr 2026.
- 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.
2 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 MVR-C5252 in people with Recurrent High Grade Glioma, run by Duke University at 2 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 24 inclusion and 16 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 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 2 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?
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 Mustafa Khasraw, MD (919 684 5301, mustafa.khasraw@duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1: Proportion of patients with dose-limiting toxicity (DLT) during the single infusion (time frame: Day 1 of treatment until 28 days post first infusion). The study lists 5 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 15 Apr 2026.