Recruiting
Phase 1

rHSC-DIPGVax & Checkpoint Blockade

Sponsor:

Ann & Robert H Lurie Children's Hospital of Chicago

Code:

NCT04943848

Conditions

Diffuse Intrinsic Pontine Glioma

Diffuse Midline Glioma, H3 K27M-Mutant

Eligibility Criteria

Sex: All

Age: 1 - 18

Healthy Volunteers: Not accepted

Interventions

rHSC-DIPGVax

Balstilimab

Zalifrelimab

Study Details

Brief 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 tumors. Newly diagnosed patients with DIPG and DMG who have completed radiation six to ten weeks prior to enrollment are eligible.

Conditions

Diffuse Intrinsic Pontine Glioma

Diffuse Midline Glioma, H3 K27M-Mutant

Study ID

NCT04943848

Start date

Jan 10, 2022

Status verified date

Mar, 2026

Completion date

Sep, 2027

Anticipated

Primary completion date

Sep, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 1 - 18

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

36 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: "Lead In": rHSC-DIPGVax Monotherapy

rHSC-DIPGVax for 8 total doses

experimental: Part A: rHSC-DIPGVax in Combination with BALSTILIMAB (Anti-PD1)

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.

experimental: Part B: Dose Escalation of ZALIFRELIMAB (Anti-CTLA4)

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.

experimental: Part C: Dose Expansion

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.

Interventions

rHSC-DIPGVax

Off-the-shelf, neoantigen heat shock protein vaccine

Balstilimab

BALSTILIMAB is a human monoclonal antibody that targets programmed cell death 1 (PD1)

Zalifrelimab

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)

Primary outcome measure

  • Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax [ Time Frame: DLT period of 28 days for rHSC-DIPGVax monotherapy ]
  • Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax plus BALSTILIMAB [ Time Frame: DLT period of 28 days for Part A ]
  • Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax plus BALSTILIMAB and ZALIFRELIMAB [ Time Frame: DLT period of 42 days for Part B ]

Central Contacts and Locations

Central contacts

Monica Newmark, BS, RN

312-227-4847MNewmark@luriechildrens.org

Ashley Plant-Fox, MD

312-227-4858aplant@luriechildrens.org

Locations

Children's Health Orange County (CHOC)

Recruiting

Orange, California, United States, 92868

Contacts

Mariko Sato, MD

714-509-8636mariko.sato@choc.org

Claudia Mousa

714-509-8724claudia.mousa@choc.org

Principal Investigator:

Mariko Sato, MD

Ann and Robert H. Lurie Children's Hospital of Chicago

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Ashley S Plant, MD

312-227-4090aplant@luriechildrens.org

Monica Newmark, BS

312-227-4847mnewmark@luriechildrens.org

Principal Investigator:

Ashley S Plant, MD

Dana-Farber Boston Children's Cancer and Blood Disorders Center

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Alexa E Stathis

857-215-1558alexae_stathis@dfci.harvard.edu

Susan Chi, MD

617-632-4386susan_chi@dfci.harvard.edu

Principal Investigator:

Susan Chi, MD

More Information

Sponsor

Ann & Robert H Lurie Children's Hospital of Chicago

Last update posted

Mar 17, 2026

Last verified

Mar, 2026

Keywords

  • Immunotherapy
  • Cancer vaccine
  • Checkpoint blockade
  • DIPG
  • Diffuse intrinsic pontine glioma
  • High grade glioma
  • DMG
  • Diffuse midline glioma
  • rHSC-DIPGVax
  • Balstilimab
  • Zalifrelimab

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Ann & Robert H Lurie Children's Hospital of Chicago on 2026-03-17.