rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG
Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant
About this trial
This is an interventional treatment trial for Diffuse Intrinsic Pontine Glioma focused on measuring Immunotherapy, Cancer vaccine, Checkpoint blockade, DIPG, Diffuse intrinsic pontine glioma, High grade glioma, DMG, Diffuse midline glioma, rHSC-DIPGVax, Balstilimab, Zalifrelimab
Eligibility Criteria
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
Sites / Locations
- Children's Health Orange County (CHOC)Recruiting
- Ann and Robert H. Lurie Children's Hospital of ChicagoRecruiting
- Dana-Farber Boston Children's Cancer and Blood Disorders CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
"Lead In": rHSC-DIPGVax Monotherapy
Part A: rHSC-DIPGVax in Combination with BALSTILIMAB (Anti-PD1)
Part B: Dose Escalation of ZALIFRELIMAB (Anti-CTLA4)
Part C: Dose Expansion
rHSC-DIPGVax for 8 total doses
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.
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.
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.