Personalized Vaccine for Patients With Recurrent Malignant Glioma

Study Overview
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Brief Summary
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A single-arm, single-center, open-labeled study will be conducted with an aim to investigate the feasibility, safety, and efficacy of the personalized vaccine for patients with recurrent malignant glioma.

Official Title
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Personalized Vaccine for Patients With Recurrent Malignant Glioma: a Single-arm, Single-center, Open-labeled Study

Conditions
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Malignant Glioma, Recurrent Glioma

Intervention / Treatment
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* Biological: personalized vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-70; signed inform consent; patients with recurrent malignant glioma; have received surgery, radiotherapy, chemotherapy; patients' tumor tissue should have a high mutation load(>10 TMB); be genetically unstable; at least have 10 neoantigens; should be able to provide tumor tissue and peripheral blood for sequencing and flow cytometry analysis; at least three months post last operation; one month after the completion of the last anti-drug therapy or radiotherapy; have not received any immune therapy; at least have one measurable lesion; KPS >60; estimated survival > 3 months patients should have adequate organ and bone marrow function; Exclusion Criteria: female patient is breastfeeding or pregnant; known history of allergy to peptides or other stimulating factors (i.e. GM-CSF); known history of Graft-Versus-Host Disease (GVHD); participation in gene therapy; other malignancy; systemic disease: i.e., severe infection; HIV; other conditions upon investigator's judgement;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: personalized vaccine<br>patients with recurrent malignant gliomas enrolled into this arm will receive the personalized vaccine through sub-cutaneous. | Biological: personalized vaccine<br>* Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced; patients would be vaccinated on day 1, 4, 8 ,15, 22 and then on week 12, 20.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidences of advent events and severe advent events | would be monitored and measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.X.) | from initiation of study treatment to 28 weeks post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| object response rate (ORR) according to iRANO criteria | ORR including complete response (CR) and partial response (PR) would be assessed and measured based on the conditions proposed by iRANO criteria | from initiation of study treatment to 24 weeks post-vaccination (last shot) | 
| progression free survival (PFS) | time interval (measured in weeks) between initiation of study treatment to progression of disease | up to 48 weeks post-vaccination(last shot) | 
| overall survival (OS) | time interval (measured in weeks) from initiation of study treatment to the death of patients | up to 48 weeks post-vaccination(last shot) | 
| immune response based on the criteria encoded by GRT-C903 and GRT-R904 | humoral and cellular immune responses including generation of specific antibodies, inflammatory factors, immune cells, will be measured as proposed by GRT-C903 and GRT-R904 | Baseline to end of treatment (up to approximately 12 months) |