NCT03914768

Immune Modulatory DC Vaccine Against Brain Tumor

Immune Modulatory DC Vaccine Against Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma (GBM)

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Shenzhen Geno-Immune Medical Institute · Academic / Other
• Sex: All
• Age: 1 Year – 75 Years
• Healthy volunteers: Not accepted

Summary

This study is designed to treat patients who have been diagnosed with brain cancer, including glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). The treatment uses immunomodulatory vaccine generated by autologous dendritic cells (DCs) pulsed with genetically modified tumor cells or tumor-related antigens including neoantigens to inject into patients. Vaccine-induced T cell responses have been associated with improved survival. The study will evaluate the safety and potential benefit of the novel immunomodulatory DC vaccines.

Detailed description

Diffuse intrinsic pontine glioma (DIPG) or glioblastoma (GBM) is an aggressive malignancy. DIPG mainly occurs in the ventral pontine of childhood. The overall median survival time is 9 to 11 months. The 2-year survival rate is less than 10%. Thus DIPG has become one of the most fatal diseases in children. These tumors invade and infiltrate the surrounding brain, making complete surgical excision impossible. Several studies focused on the identification of GBM or DIPG-specific antigens and evaluated their potential for vaccine application. Immunomodulatory DC vaccines based on ex vivo genetic modifications in combination with known tumor-specific antigens may substantially enhance the activation potential of tumor-specific T cells with improved benefit to patients. Although certain antigens are highly specific in DIPG or GBM, existing immune tolerance suppresses anti-tumor immunity in cancer patients. To induce anti-cancer immune response in patients, ex vivo modification of immune modulatory antigens or immune cells will be necessary. Advanced whole exome sequencing has been developed to identify specific mutations in tumors and predict best-fit MHC-specific neoepitopes for T cell activation. In this study we will investigate novel DC vaccines based on autologous DCs pulsed with genetically modified tumor cells or related antigens such as neoantigens to induce a strong anti-tumor immunity. Early studies of DC-based vaccines targeting gliomas have shown acceptable safety and low toxicity profile. This is a multi-center randomized Phase I study to evaluate safety of novel DC vaccines.

Conditions

• Diffuse Intrinsic Pontine Glioma or Glioblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Immunomodulatory DC vaccine to target DIPG and GBM	This study will inject DC vaccine cells near lymphoid tissue close to the tumor. The patient will receive intravenous cyclophosphamide (200 mg/m2) or oral (cytoxan) before the vaccine, followed by DC vaccine and intravenous bevacizumab (15 mg/kg) the next day. The cells will be repeatedly infused every month for six consecutive months depending on the response and the condition of the patient. The amount of DC vaccine cells per injection is based on prior report at 5-10x106. An initial dose escalation scheme will be imposed.

Timeline

• Start date: 2019-03-31
• Primary completion: 2021-01-31
• Completion: 2022-12-31
• First posted: 2019-04-16
• Last updated: 2020-06-12

Locations

3 sites across 1 country: China