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

Primary Purpose

Glioblastoma Multiforme of Brain

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Autologous dendritic cells pulsed with multiple neoantigen peptides.

Temozolomide adjuvant chemotherapy

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme of Brain

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age from 18 to 75 years (including 18 and 75 years old);
Newly-diagnosed glioblastoma confirmed by histopathological exams;
IDH1- and IDH2-wild-type gliomas;
Extent of resection of enhancing lesions > 90%;
Karnofsky Performance Score(KPS) ≥ 60%;
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:

Subjects with any other active malignancy;
Subjects received the placement of Carmustine implants within 6 months before the inclusion;
Subjects with active HBC, HCV or HIV infection;
Subjects with grade 2 -3 hypertension or uncontrolled hypertension;
Subjects with severe cardio- or cerebro- vascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.;
Subjects with uncontrolled autoimmune diseases such as hemolytic anemia, psoriasis and rheumatoid arthritis, etc.;
Subjects with severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes;
Subjects receiving immunosuppressants after organ transplantation;
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);
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;
Subjects in pregnancy or breastfeeding, or those who plan to become pregnant during treatment or within 2 months after the end of treatment;
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);
Subjects who have received other vaccine therapies or gene-modified cell therapy before enrollment;
Subjects with number of the predicted neoantigen peptides less than 5;
Subjects with other conditions that would interfere trial participation at the investigator's discretion;
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;
Subjects who participated or are participating in other clinical trials within 4 weeks before enrollment.

Sites / Locations

Beijing Tiantan HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DC vaccine group

Arm Description

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

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events (AEs)

AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Secondary Outcome Measures

Proportions of patients with positive peripheral tumor specific immune response after the DC vaccinations

The peripheral tumor specific immune response is measured by the IFN-γ release ELISPOT assay, using the peripheral blood mononuclear cells (PBMCs) that are collected before the vaccine injection (baseline), one week after the 3r, 5th and the last injection, respectively. The positive response is defined as "≥ 55 spot-forming cells in each million PBMCs" or "number of spot-forming cells increase by 3-fold after the DC vaccination compared with the baseline".

Progression-free survival

months from the date of surgery to tumor recurrence or progression

Overall survival

months from the date of surgery to death

Rate of the patients who survive for more than one year after surgery in all the included patients who receive the DC vaccine

One-year survival rate

Full Information

NCT ID

NCT04968366

First Posted

July 6, 2021

Last Updated

July 25, 2023

Sponsor

Beijing Tiantan Hospital

Collaborators

ZhongSheng BioTech Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04968366

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 30, 2021 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Beijing Tiantan Hospital

Collaborators

ZhongSheng BioTech Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme of Brain

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

DC vaccine group

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Autologous dendritic cells pulsed with multiple neoantigen peptides.

Intervention Description

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

Drug

Intervention Name(s)

Temozolomide adjuvant chemotherapy

Other Intervention Name(s)

the standard-of-care adjuvant chemotherapy for GBM patients

Intervention Description

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

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events (AEs)

Description

AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Time Frame

All the AEs were recorded from the first shot to 8 weeks after the last shot.

Secondary Outcome Measure Information:

Title

Proportions of patients with positive peripheral tumor specific immune response after the DC vaccinations

Description

Time Frame

start from the inclusion timepoint to one week after the last injection.

Title

Progression-free survival

Description

months from the date of surgery to tumor recurrence or progression

Time Frame

From date of surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Title

Overall survival

Description

months from the date of surgery to death

Time Frame

From date of surgery until the date of death from any cause, assessed up to 60 months

Title

Rate of the patients who survive for more than one year after surgery in all the included patients who receive the DC vaccine

Description

One-year survival rate

Time Frame

From date of surgery until one year after surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age from 18 to 75 years (including 18 and 75 years old); Newly-diagnosed glioblastoma confirmed by histopathological exams; IDH1- and IDH2-wild-type gliomas; Extent of resection of enhancing lesions > 90%; Karnofsky Performance Score(KPS) ≥ 60%; 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: Subjects with any other active malignancy; Subjects received the placement of Carmustine implants within 6 months before the inclusion; Subjects with active HBC, HCV or HIV infection; Subjects with grade 2 -3 hypertension or uncontrolled hypertension; Subjects with severe cardio- or cerebro- vascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.; Subjects with uncontrolled autoimmune diseases such as hemolytic anemia, psoriasis and rheumatoid arthritis, etc.; Subjects with severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes; Subjects receiving immunosuppressants after organ transplantation; 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); 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; Subjects in pregnancy or breastfeeding, or those who plan to become pregnant during treatment or within 2 months after the end of treatment; 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); Subjects who have received other vaccine therapies or gene-modified cell therapy before enrollment; Subjects with number of the predicted neoantigen peptides less than 5; Subjects with other conditions that would interfere trial participation at the investigator's discretion; 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; Subjects who participated or are participating in other clinical trials within 4 weeks before enrollment.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yang Zhang, Dr.

Phone

01059976516

zhangyang8025@yeah.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nan Ji, Dr.

Organizational Affiliation

Beijing Tiantan Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Tiantan Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100730

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yang Zhang, Dr.

Phone

010-59976516

zhangyang8025@yeah.net

First Name & Middle Initial & Last Name & Degree

Nan Ji, Dr.

First Name & Middle Initial & Last Name & Degree

Yang Zhang, Dr.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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