Diffuse Intrinsic Pontine GliomaPhase 1NCT04943848
rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG
A Phase 1 study testing rHSC-DIPGVax, Balstilimab and Zalifrelimab in people with Diffuse Intrinsic Pontine Glioma and Diffuse Midline Glioma, H3 K27M-Mutant, run by Ann & Robert H Lurie Children's Hospital of Chicago at 3 sites in United States.
Trial summary
This is a phase I, open label, plus expansion clinical trial evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB. rHSC-DIPGVax is an off-the-shelf neo-antigen heat shock protein containing 16 peptides reflecting neo-epitopes found in the majority of DIPG and DMG… Read more about this study
- Who is it for?
- Ages 12 months to 18 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant
- What is being tested?
- rHSC-DIPGVax, Balstilimab and Zalifrelimab
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 3 sitesUnited States
- Study dates
- 10 Jan 2022to Sep 2027
- Phase
- Phase 1
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 12 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects with newly diagnosed typical or non-typical, biopsy-proven DIPG or DMG are eligible for study enrollment. Biopsy is not required for subjects with radiographically typical DIPG meeting imaging criteria. Biopsy is required for DMG's and non-radiographically typical DIPG. Histone mutation must be confirmed by pathology report. Radiographically typical DIPG defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons.
- = Subjects ages > or = to 12 months and < or = 18 years ("Lead In", Part A, and Part B require first three patients be > or = to 12 years of age)
- BSA > or = 0.35m2 at the time of study enrollment
- Performance score: Karnofsky >50% of subjects >16 years of age and Lansky > or = 50 for subjects < or = 16 years of age. Subjects who are unable to walk because of paralysis but are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
- Must start radiation therapy within 42 days from date of diagnostic imaging. C1D1 must be within 42 days to 70 days post radiation (6-10 weeks). Patients CANNOT receive temozolomide during radiation
- Corticosteroids should be weaned as tolerated after radiation therapy with the goal of < or = 0.5mg/kg/day for a minimum of 7 days prior to enrollment.
- Subjects must have measurable disease
Who cannot join
- Patients cannot receive temozolomide during radiation
- Disseminated disease
- Subjects who have received any cancer therapy except for radiation
- Autoimmune or immune disorders
- Active respiratory disorder or infection
- Active viral infection
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Dana-Farber Boston Children's Cancer and Blood Disorders Center
Boston, Massachusetts, 02215
Alexa E Stathis, 857-215-1558, alexae_stathis@dfci.harvard.edu
Susan Chi, MD, 617-632-4386, susan_chi@dfci.harvard.edu
- Recruiting
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Ashley S Plant, MD, 312-227-4090, aplant@luriechildrens.org
Monica Newmark, BS, 312-227-4847, mnewmark@luriechildrens.org
- Recruiting
Children's Health Orange County (CHOC)
Orange, California, 92868
Mariko Sato, MD, 714-509-8636, mariko.sato@choc.org
Claudia Mousa, 714-509-8724, claudia.mousa@choc.org
About this study
Official title: A Phase I Clinical Trial of Neo-antigen Heat Shock Protein Vaccine (rHSC-DIPGVax) in Combination With Checkpoint Blockade for the Treatment of Diffuse Intrinsic Pontine Glioma (DIPG) and Diffuse Midline Glioma in Childhood
This is a phase I, open label, plus expansion clinical trial evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB. rHSC-DIPGVax is an off-the-shelf neo-antigen heat shock protein containing 16 peptides reflecting neo-epitopes found in the majority of DIPG and DMG tumors. Newly diagnosed patients with DIPG and DMG who have completed radiation six to ten weeks prior to enrollment are eligible.
Read the detailed description
This is a phase I, open label, plus expansion clinical trial evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB using a 3+3 design for subjects with newly diagnosed DIPG or DMG following completion of radiation therapy. Given this is a first in-human study of rHSC-DIPGVax, an initial study "Lead In" will assess the tolerability of vaccine monotherapy first in older children (ages 5 to 18 years of age) followed by younger children (12 months to 18 years of age).
Sequential Parts A and B of this study will also first enroll patients ages 5 to 18 years of age before enrolling younger children. The rationale for the combination of vaccine and anti-PD1 therapy includes evidence of a more profound intra-tumoral response with addition of inhibition of negative co-regulatory pathways, such as, PD1/PDL1 and the need to overcome potentially immunosuppressive or immune "cold" microenvironment of gliomas. Anti-CLTA4 therapy will also be combined with rHSC-DIPGVax in the dose escalation portion of this study because of the ability of anti-CTLA4 therapy to induce T cell priming to promote T memory formation. Given the lack of standard treatment options for DIPG and DMG patients, this clinical trial will use combinatorial immunotherapy in upfront treatment of these patients in hopes of maximizing potential efficacy in this at-risk population while still assessing safety throughout.
Part A will evaluate rHSC-DIPGVax plus BALSTILIMAB. Pharmacokinetics (PK) of BALSTILIMAB will also be evaluated to assess exposure. If the rHSC-DIPGVax plus BALSTILIMAB is well tolerated in Part A for 28-days, this study will then move to enrolling Part B to evaluate the safety and tolerability of rHSC-DIPGVax and BALSTILIMAB in combination with ZALIFRELIMAB at two dose levels for a total therapy duration of one year or twenty-seven cycles, whichever occurs first.
Advancement from Part A to Part B and dose escalation in Part B will follow a conservative 3+3 design. The dose limiting toxicity (DLT) monitoring period will last 28 days (2 cycles) for Part A subjects and 42 days (1 cycle) for Part B. Subjects will be allowed to continue on in Part A for twenty-seven 14-day cycles or nine 42-day cycles in Part B or 1 year of total therapy, whichever comes first.
After the RP2D of ZALIFRELIMAB is determined, Part C, the expansion arm, will enroll further subjects at this dose level to assess futility versus efficacy. All subjects in trial Part C will be monitored for dose limiting toxicities for the duration of their participation in the study to monitor for excess toxicity.
- Being tested
- rHSC-DIPGVax, Balstilimab, Zalifrelimab
- Keywords
- Immunotherapy, Cancer vaccine, Checkpoint blockade, DIPG, Diffuse intrinsic pontine glioma, High grade glioma, DMG, Diffuse midline glioma, rHSC-DIPGVax, Balstilimab, Zalifrelimab
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rHSC-DIPGVaxBiological
Also called vaccine
Off-the-shelf, neoantigen heat shock protein vaccine
BalstilimabDrug
Also called checkpoint blockade, anti-PD1
BALSTILIMAB is a human monoclonal antibody that targets programmed cell death 1 (PD1)
ZalifrelimabDrug
Also called checkpoint blockade, anti-CTLA4
ZALIFRELIMAB is a human monoclonal immunoglobulin G1k subclass (IgG1k) antibody that specifically recognizes cytotoxic T lymphocyte-associated protein 4 (CTLA-4, also known as CD152)
| Study group | Role | What they receive |
|---|---|---|
| "Lead In": rHSC-DIPGVax Monotherapy | Experimental | rHSC-DIPGVax for 8 total doses Receives: Biological: rHSC-DIPGVax |
| Part A: rHSC-DIPGVax in Combination with BALSTILIMAB (Anti-PD1) | Experimental | rHSC-DIPGVax (8 total doses) + BALSTILIMAB (1 year of therapy or 27 cycles, whichever comes first)
Patients will enroll 6-10 weeks post standard of care (SOC) radiation completion. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. The first 3 patients must be 5 years or older to 18. Subsequently, subjects ages 12 months to 18 years can be enrolled. Up to six patients will be enrolled on Part A. Once safety is established for rHSC-DIPGVax plus anti-PD1 (BALSTILIMAB), the study will proceed to Part B. Receives: Biological: rHSC-DIPGVax; Drug: Balstilimab |
| Part B: Dose Escalation of ZALIFRELIMAB (Anti-CTLA4) | Experimental | rHSC-DIPGVax (8 total doses) + BALSTILIMAB + ZALIFRELIMAB (1 year of therapy or 9 cycles, whichever comes first)
Patients will enroll 6-10 weeks post standard of care (SOC) radiation therapy. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. The first 3 patients must be 5 years or older to 18. Subsequently, subjects ages 12 months to 18 years can be enrolled. Up to 12 patients will be enrolled on Part B. Once safety is established for rHSC-DIPGVax plus anti-PD1 (BALSTILIMAB) plus anti-CTLA4 (ZALIFRELIMAB), the study will proceed to Part C. Receives: Biological: rHSC-DIPGVax; Drug: Balstilimab; Drug: Zalifrelimab |
| Part C: Dose Expansion | Experimental | rHSC-DIPGVax (8 total doses) + BALSTILIMAB + ZALIFRELIMAB (at RP2D from Part B) (1 year of therapy or 9 cycles, whichever comes first)
Patients will enroll 6-10 weeks post standard of care (SOC) radiation therapy. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. Up to 12 patients will be enrolled on Part C. All subjects in Part C will be monitored for DLT's for the duration of their participation in the study to monitor for excess toxicity. Receives: Biological: rHSC-DIPGVax; Drug: Balstilimab; Drug: Zalifrelimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax
Number of DLT's per CTCAE version 5.0 and iRANO guidelines.
Measured: DLT period of 28 days for rHSC-DIPGVax monotherapy
Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax plus BALSTILIMAB
Number of DLT's per CTCAE version 5.0 and iRANO guidelines.
Measured: DLT period of 28 days for Part A
Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax plus BALSTILIMAB and ZALIFRELIMAB
Number of DLT's per CTCAE version 5.0 and iRANO guidelines.
Measured: DLT period of 42 days for Part B
Secondary outcomes (4)
Total number of DLT's for ZALIFRELIMAB at RP2D in combination with rHSC-DIPGVax and BALSTILIMAB
Number of DLT's using CTCAE version 5.0 and iRANO guidelines
Measured: On-going during 1 year of therapy plus 3 month follow up
To evaluate the efficacy of the combination of rHSC-DIPGVax, BALSTILIMAB, and ZALIFRELIMB in pediatric subjects with DIPG and DMG as measured by overall survival at 12 months and time-to-progression as measured from time of diagnostic imaging
12 month overall survival
Measured: On-going during 1 year of therapy plus 3 month follow up
Overall survival at 1 year
Overall survival from time of diagnostic imaging to time of death
Measured: On-going during 1 year of therapy
Time to progression
time to progression (from time of diagnostic imaging to time of disease progression)
Measured: On-going during 1 year of therapy plus up to 5 years off treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2021
- Study start10 Jan 2022
- Primary completionSep 2026 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Intrinsic Pontine GliomaStudies 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Phase I, open label, plus expansion clinical trial
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Children's Hospital of Orange County, University of Calgary
- Responsible party
- Sponsor
- Investigators
- Ashley Plant-Fox, MD, Principal investigator, Ann and Robert H. Lurie Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04943848
- Sponsor's protocol ID
- LCH 20C05
- Status last verified
- Mar 2026
- First submitted
- 24 May 2021
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No