Immune Modulatory DC Vaccine Against Brain Tumor
Primary Purpose
Diffuse Intrinsic Pontine Glioma or Glioblastoma
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Immunomodulatory DC vaccine to target DIPG and GBM
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Intrinsic Pontine Glioma or Glioblastoma focused on measuring DC vaccine therapy, DIPG, GBM, neoantigen
Eligibility Criteria
Inclusion Criteria:
- Abilities to understand and the willingness to provide written informed consent. Assent will be obtained when appropriate based on the subjects age;
- Patients are ≥ 6 months and ≤ 80 years old;
- DIPG or GBM patients with existing or measurable tumors in the brain. Patients have received standard care of medication, such as gross total resection with concurrent radio chemotherapy (~54 - 60 Gy, TMZ);
- Patients with adequate neurological function and epileptic symptoms that are well controlled;
- Observing the condition after surgery or without surgery;
- Karnofsky performance score (KPS) ≥ 60;Life expectancy >3 months;
- Important organ function is satisfied: Cardiac ultrasound indicates a cardiac ejection fraction ≥50%; and there is no obvious abnormality in the electrocardiogram; blood oxygen saturation ≥90%; creatinine <2.5 times normal range; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 times normal range; Total bilirubin ≤ 2.0 mg / dl; Hgb (hemoglobin) ≥ 80g / L;
- Peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
- Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if seizure disorder is well controlled;
- Patients must be willing to follow the orders of doctors.
Exclusion Criteria:
- A prior history of gliadel implantation 4 weeks before this study start or antibody based therapies;
- The patient was still using dexamethasone at a dose greater than 4 mg/day during mononuclear cell collection;
- Patients have a history of autoimmune diseases or other diseases requiring long-term use of hormones or immunosuppressive drugs;
- Patients with a history of allergies or allergies to immune cells and adjuvants of cellular products;
- Active infection with fever;
- Patients with neutropenia (> 10 days) that are difficult to correct after treatment;
- Infection with bacteria, fungi or viruses, uncontrolled;
- Patients with HIV and those living with active HBV and HCV;
- Pregnant, pregnant and lactating women;
- Important organ failure (heart, liver, kidney, lung);
- Patients who had previously been treated with cell therapy but were ineffective after physical examination were discussed and confirmed by team experts and were not suitable for re-treatment;
- Anything that researchers believe may increase the risk of subjects or interfere with test results.
Sites / Locations
- Shenzhen Geno-immune Medical Institute
- Shenzhen Children's Hospital
- Department of Neurosurgery, Shenzhen Hospital, Southern Medical University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Immunomodulatory DC vaccine to target DIPG and GBM
Arm Description
Patients will receive immune modulatory treatment consisting of cyclophosphamide (200 mg/m2) and bevacizumab (15 mg/kg), before and after DC vaccine injection, respectively.
Outcomes
Primary Outcome Measures
Safety of infusion of autologous immunomodulatory DC Vaccine is assessed by the NCI CTCAE V4.0 criteria.
Safety of the vaccine will be assessed by monitoring for adverse events (AEs) based on scheduled laboratory assessments.
Overall survival (OS) at 12 months (OS12).
OS12 will be the clinical efficacy primary endpoint. For subjects who are still alive at 12 months, OS12 will be censored at the last contact date. OS will be estimated using the Kaplan-Meier method.
Secondary Outcome Measures
Treatment response rate of DIPG or GBM
Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on brain MRI imaging analysis.
Overall survival Rate
Percentage of participants with objective response as determined by the investigator based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
Progression-free survival rate
Progression-free Survival (PFS) as determined by the investigator based on RECIST v1.1
ELISPOT or antigen specific functional assays for evaluation of antigen specific immune response in patients
Tumor antigen specific immune response in the peripheral blood evaluated by ELISPOT or antigen specific functional assays.
Magnetic resonance imaging for evaluation of disease progression and prognosis
The prognosis of GBM or DIPG will be determined by MRI
Full Information
NCT ID
NCT03914768
First Posted
April 11, 2019
Last Updated
June 10, 2020
Sponsor
Shenzhen Geno-Immune Medical Institute
Collaborators
Shenzhen Hospital of Southern Medical University, Shenzhen Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03914768
Brief Title
Immune Modulatory DC Vaccine Against Brain Tumor
Official Title
Immune Modulatory DC Vaccine Against Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma (GBM)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 31, 2019 (Actual)
Primary Completion Date
January 31, 2021 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shenzhen Geno-Immune Medical Institute
Collaborators
Shenzhen Hospital of Southern Medical University, Shenzhen Children's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Intrinsic Pontine Glioma or Glioblastoma
Keywords
DC vaccine therapy, DIPG, GBM, neoantigen
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Patients with DIPG or GBM will be treated with immunomodulatory DC vaccine
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Immunomodulatory DC vaccine to target DIPG and GBM
Arm Type
Experimental
Arm Description
Patients will receive immune modulatory treatment consisting of cyclophosphamide (200 mg/m2) and bevacizumab (15 mg/kg), before and after DC vaccine injection, respectively.
Intervention Type
Biological
Intervention Name(s)
Immunomodulatory DC vaccine to target DIPG and GBM
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety of infusion of autologous immunomodulatory DC Vaccine is assessed by the NCI CTCAE V4.0 criteria.
Description
Safety of the vaccine will be assessed by monitoring for adverse events (AEs) based on scheduled laboratory assessments.
Time Frame
2 years
Title
Overall survival (OS) at 12 months (OS12).
Description
OS12 will be the clinical efficacy primary endpoint. For subjects who are still alive at 12 months, OS12 will be censored at the last contact date. OS will be estimated using the Kaplan-Meier method.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Treatment response rate of DIPG or GBM
Description
Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on brain MRI imaging analysis.
Time Frame
6 months]
Title
Overall survival Rate
Description
Percentage of participants with objective response as determined by the investigator based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame
1 year follow up
Title
Progression-free survival rate
Description
Progression-free Survival (PFS) as determined by the investigator based on RECIST v1.1
Time Frame
1 years
Title
ELISPOT or antigen specific functional assays for evaluation of antigen specific immune response in patients
Description
Tumor antigen specific immune response in the peripheral blood evaluated by ELISPOT or antigen specific functional assays.
Time Frame
1 year
Title
Magnetic resonance imaging for evaluation of disease progression and prognosis
Description
The prognosis of GBM or DIPG will be determined by MRI
Time Frame
1 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Abilities to understand and the willingness to provide written informed consent. Assent will be obtained when appropriate based on the subjects age;
Patients are ≥ 6 months and ≤ 80 years old;
DIPG or GBM patients with existing or measurable tumors in the brain. Patients have received standard care of medication, such as gross total resection with concurrent radio chemotherapy (~54 - 60 Gy, TMZ);
Patients with adequate neurological function and epileptic symptoms that are well controlled;
Observing the condition after surgery or without surgery;
Karnofsky performance score (KPS) ≥ 60;Life expectancy >3 months;
Important organ function is satisfied: Cardiac ultrasound indicates a cardiac ejection fraction ≥50%; and there is no obvious abnormality in the electrocardiogram; blood oxygen saturation ≥90%; creatinine <2.5 times normal range; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 times normal range; Total bilirubin ≤ 2.0 mg / dl; Hgb (hemoglobin) ≥ 80g / L;
Peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if seizure disorder is well controlled;
Patients must be willing to follow the orders of doctors.
Exclusion Criteria:
A prior history of gliadel implantation 4 weeks before this study start or antibody based therapies;
The patient was still using dexamethasone at a dose greater than 4 mg/day during mononuclear cell collection;
Patients have a history of autoimmune diseases or other diseases requiring long-term use of hormones or immunosuppressive drugs;
Patients with a history of allergies or allergies to immune cells and adjuvants of cellular products;
Active infection with fever;
Patients with neutropenia (> 10 days) that are difficult to correct after treatment;
Infection with bacteria, fungi or viruses, uncontrolled;
Patients with HIV and those living with active HBV and HCV;
Pregnant, pregnant and lactating women;
Important organ failure (heart, liver, kidney, lung);
Patients who had previously been treated with cell therapy but were ineffective after physical examination were discussed and confirmed by team experts and were not suitable for re-treatment;
Anything that researchers believe may increase the risk of subjects or interfere with test results.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lung-Ji Chang, PhD
Organizational Affiliation
Shenzhen Geno-Immune Medical Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shenzhen Geno-immune Medical Institute
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518000
Country
China
Facility Name
Shenzhen Children's Hospital
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518038
Country
China
Facility Name
Department of Neurosurgery, Shenzhen Hospital, Southern Medical University
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518100
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
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Immune Modulatory DC Vaccine Against Brain Tumor
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