Safety & Efficacy of DC Vaccine and TMZ for the Treatment of Newly-diagnosed Glioblastoma After Surgery

NCT ID: NCT04968366

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-30
• Study Completion Date: 2028-12-31

Brief Summary

This is a single-center, single-arm phase I study to determine the safety and preliminary efficacy of autologous dendritic cells (DCs) loaded with multiple tumor neoantigen peptides administered as a cancer-treatment vaccine to treat adult postoperative patients with newly-diagnosed glioblastoma, in combination with the standard-of-care Temozolomide (TMZ) chemotherapy.

Detailed Description

This is a single-center, single-arm phase I study to determine the safety and preliminary efficacy of autologous dendritic cells (DCs) loaded with multiple tumor neoantigen peptides administered as a cancer-treatment vaccination for the treatment of newly-diagnosed glioblastoma (GBM). The subjects are adult GBM patients who have undergone surgical resection. After the completion of TMZ concurrent chemoradiation, and, during conventional adjuvant TMZ chemotherapy, subjects will receive autologous DC vaccine treatments as scheduled. Ten subjects will be enrolled. The autologous genetic-modification-free DC cells will be loaded with multiple tumor neoantigen peptides and administered (i.d) to subjects. After 5 injections, the investigator will review subject's tolerance and compliance, and decide whether or not to administer more DC vaccines up to 8 injections. For certain patients with good tolerance and clinical response of the DC vaccine, peripheral blood is extracted after completion of TMZ adjuvant chemotherapy to assess patient's immune response. According to the result, investigators will be decided whether to perform more 1-2 treatment cycles (5-8 infections/cycle) to strengthen the effectiveness.

Conditions

Glioblastoma Multiforme of Brain

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DC vaccine group

Subjects will receive five to eight doses of the DC vaccine through i.d. injection into regions near to the groin and axillary during they receive TMZ adjuvant chemotherapy

Group Type: EXPERIMENTAL

Autologous dendritic cells pulsed with multiple neoantigen peptides.

Intervention Type: BIOLOGICAL

Each dosage of Dendritic Cells (DC) vaccine contains 2-10 million DC cells, loaded with 5-20 tumor neoantigen peptides. DC vaccine will be administered (i.d) around lymph nodes of the groin and Axillary at 2nd, 3rd, 4th, 7th and 11th week after the completion of concurrent Temozolomide chemoradiation. After 5 injections, the investigator will review subject's tolerance and compliance; and, decide whether to administer more DC vaccines up to 8 injections. For certain patients with good tolerance and clinical response of the DC vaccine, peripheral blood is extracted after completion of Temozolomide adjuvant chemotherapy to assess the patient's immune response. According to the result, investigators will decide whether to perform 1-2 more treatment cycles (5-8 injections/cycle) to strengthen the effectiveness

Temozolomide adjuvant chemotherapy

Intervention Type: DRUG

Temozolomide is administered as the standard-of-care adjuvant chemotherapy, in combination with the DC vaccines to treat the enrolled patients.

Interventions

Autologous dendritic cells pulsed with multiple neoantigen peptides.

Each dosage of Dendritic Cells (DC) vaccine contains 2-10 million DC cells, loaded with 5-20 tumor neoantigen peptides. DC vaccine will be administered (i.d) around lymph nodes of the groin and Axillary at 2nd, 3rd, 4th, 7th and 11th week after the completion of concurrent Temozolomide chemoradiation. After 5 injections, the investigator will review subject's tolerance and compliance; and, decide whether to administer more DC vaccines up to 8 injections. For certain patients with good tolerance and clinical response of the DC vaccine, peripheral blood is extracted after completion of Temozolomide adjuvant chemotherapy to assess the patient's immune response. According to the result, investigators will decide whether to perform 1-2 more treatment cycles (5-8 injections/cycle) to strengthen the effectiveness

Intervention Type: BIOLOGICAL

Temozolomide adjuvant chemotherapy

Temozolomide is administered as the standard-of-care adjuvant chemotherapy, in combination with the DC vaccines to treat the enrolled patients.

Intervention Type: DRUG

Other Intervention Names

the standard-of-care adjuvant chemotherapy for GBM patients

Eligibility Criteria

Inclusion Criteria

1. Age from 18 to 75 years (including 18 and 75 years old);

2. Newly-diagnosed glioblastoma confirmed by histopathological exams;

3. IDH1- and IDH2-wild-type gliomas;

4. Extent of resection of enhancing lesions > 90%;

5. Karnofsky Performance Score(KPS) ≥ 60%;

6. Adequate organ functions:

The absolute value of white blood cells ≥ 2.5×10 9/L; Hemoglobin levels> 100 g/L; Platelet counts > 100×109/L; Levels of Alanine aminotransferase, aspartate aminotransferase <2.5 x ULN; Serum creatinine levels <1.5 x ULN.

Exclusion Criteria

1. Subjects with any other active malignancy;

2. Subjects received the placement of Carmustine implants within 6 months before the inclusion;

3. Subjects with active HBC, HCV or HIV infection;

4. Subjects with grade 2 -3 hypertension or uncontrolled hypertension;

5. Subjects with severe cardio- or cerebro- vascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.;

6. Subjects with uncontrolled autoimmune diseases such as hemolytic anemia, psoriasis and rheumatoid arthritis, etc.;

7. Subjects with severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes;

8. Subjects receiving immunosuppressants after organ transplantation;

9. Within four weeks before the DC vaccinations, subjects receiving systemic administration of steroids with dosage more than 10mg/d prednisone or the equivalent doses of other steroids ( not including inhaled corticosteroid);

10. Subjects with unstable pulmonary embolism, deep venous embolism, or other major arterial and venous thromboembolic events that occur within 30 days before the enrollment; receiving ongoing anticoagulant therapy;

11. Subjects in pregnancy or breastfeeding, or those who plan to become pregnant during treatment or within 2 months after the end of treatment;

12. Within the 14 days before enrollment, subjects with active infections or uncontrolled infections that require systemic antibiotic treatment (except for simple urinary tract infections or upper respiratory tract infections);

13. Subjects who have received other vaccine therapies or gene-modified cell therapy before enrollment;

14. Subjects with number of the predicted neoantigen peptides less than 5;

15. Subjects with other conditions that would interfere trial participation at the investigator's discretion;

16. Subjects with medical conditions that affect signing the written informed consent or complying with the research procedures; or patients who are unwilling or unable to comply with the research procedures;

17. Subjects who participated or are participating in other clinical trials within 4 weeks before enrollment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZhongSheng BioTech Inc.

UNKNOWN

Sponsor Role: collaborator

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yang Zhang

Chief Neurosurgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nan Ji, Dr.

Role: PRINCIPAL_INVESTIGATOR

Beijing Tiantan Hospital

Locations

Beijing Tiantan Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

KY 2021-021-02

Identifier Type: -

Identifier Source: org_study_id