NCT05457959

Peptide-Pulsed Dendritic Cell Vaccination in Combination With Nivolumab and Ipilimumab for the Treatment of Recurrent and/or Progressive Diffuse Hemispheric Glioma, H3 G34-mutant

A Placebo-Controlled, Single (Participant) Blind Trial to Evaluate the Safety, Tolerability, and Early Immunogenicity of Peptide-Pulsed Dendritic Cell Vaccination With Nivolumab and Ipilimumab in Recurrent and/or Progressive Diffuse Hemispheric Glioma, H3 G34-Mutant

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 13 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests peptide-pulsed dendritic cell vaccination in combination with immunotherapy nivolumab and ipilimumab for the treatment diffuse hemispheric glioma with a H3 G34 mutation that has come back (recurrent) and/or is growing, spreading, or getting worse (progressive). Vaccines made from the patient's own white blood cells and peptide-pulsed dendritic cells may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, also may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Together, the vaccine and immunotherapy drugs given before and after surgical resection (the removal of tumor cells through surgery) may improve stimulation of anti-tumor immunity to help fight the cancer.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of nivolumab/ipilimumab and peptide-pulsed dendritic cell (ppDC) vaccination in diffuse hemispheric glioma H3 G34-mutant (DHG) participants undergoing surgical resection. SECONDARY OBJECTIVES: I. To determine whether nivolumab/ipilimumab and/or ppDC vaccination facilitate intratumoral T cell-mediated anti-tumor immune activation in progressive DHG. II. To determine whether nivolumab/ipilimumab and/or ppDC vaccination stimulate systemic adaptive anti-tumor immunity in progressive DHG. OUTLINE: Patients are sequentially assigned to 2 cohorts. COHORT 1 (Pre-Surgical Resection): Patients are randomized to 1 of 3 arms. ARM A: Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC intradermally (ID) in both arms with poly ICLC intramuscularly (IM) on day -10 and placebo intravenously (IV) on day -9 prior to standard of care surgical resection. ARM B: Patients undergo leukapheresis 10 days prior to first injection. Patients receive placebo ID in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection. ARM C: Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID divided in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection. COHORT 2 (Post-Surgical Resection): Patients are assigned to 1 of 3 arms. ARM A: Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and placebo IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. ARM B: Within 30 days of surgical resection, patients receive placebo ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. ARM C: Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and 6 months and every 6 months for up to 2 years.

Conditions

• Diffuse Hemispheric Glioma, H3 G34-Mutant

Interventions

Type	Name	Description
BIOLOGICAL	Dendritic Cell Tumor Peptide Vaccine	Given ID
BIOLOGICAL	Ipilimumab	Given IV
PROCEDURE	Leukapheresis	Undergo leukapheresis
BIOLOGICAL	Nivolumab	Given IV
DRUG	Placebo Administration	Given ID
DRUG	Placebo Administration	Given IV
DRUG	Poly ICLC	Given IM
PROCEDURE	Resection	Undergo standard of care surgical resection

Timeline

• Start date: 2024-12-01
• Primary completion: 2029-12-01
• Completion: 2030-12-01
• First posted: 2022-07-14
• Last updated: 2025-02-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study