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Immune Modulatory DC Vaccine Against Brain Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03914768
Recruitment Status : Enrolling by invitation
First Posted : April 15, 2019
Last Update Posted : July 16, 2019
Sponsor:
Information provided by (Responsible Party):
Shenzhen Geno-Immune Medical Institute

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.

Condition or disease Intervention/treatment Phase
Diffuse Intrinsic Pontine Glioma or Glioblastoma Biological: Immunomodulatory DC vaccine to target DIPG and GBM Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Patients with DIPG or GBM will be treated with immunomodulatory DC vaccine
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Immune Modulatory DC Vaccine Against Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma (GBM)
Actual Study Start Date : March 31, 2019
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Immunomodulatory DC vaccine to target DIPG and GBM
Patients will receive immune modulatory treatment consisting of cyclophosphamide (200 mg/m2) and bevacizumab (15 mg/kg), before and after DC vaccine injection, respectively.
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.




Primary Outcome Measures :
  1. Safety of infusion of autologous immunomodulatory DC Vaccine is assessed by the NCI CTCAE V4.0 criteria. [ Time Frame: 2 years ]
    Safety of the vaccine will be assessed by monitoring for adverse events (AEs) based on scheduled laboratory assessments.

  2. Overall survival (OS) at 12 months (OS12). [ Time Frame: 12 months ]
    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 :
  1. Treatment response rate of DIPG or GBM [ Time Frame: 6 months] ]
    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.

  2. Overall survival Rate [ Time Frame: 1 year follow up ]
    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)

  3. Progression-free survival rate [ Time Frame: 1 years ]
    Progression-free Survival (PFS) as determined by the investigator based on RECIST v1.1

  4. ELISPOT or antigen specific functional assays for evaluation of antigen specific immune response in patients [ Time Frame: 1 year ]
    Tumor antigen specific immune response in the peripheral blood evaluated by ELISPOT or antigen specific functional assays.

  5. Magnetic resonance imaging for evaluation of disease progression and prognosis [ Time Frame: 1 years ]
    The prognosis of GBM or DIPG will be determined by MRI



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Abilities to understand and the willingness to provide written informed consent. Assent will be obtained when appropriate based on the subjects age;
  2. Patients are ≥ 6 months and ≤ 80 years old;
  3. 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);
  4. Patients with adequate neurological function and epileptic symptoms that are well controlled;
  5. Observing the condition after surgery or without surgery;
  6. Karnofsky performance score (KPS) ≥ 60;Life expectancy >3 months;
  7. 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;
  8. Peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
  9. Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if seizure disorder is well controlled;
  10. Patients must be willing to follow the orders of doctors.

Exclusion Criteria:

  1. A prior history of gliadel implantation 4 weeks before this study start or antibody based therapies;
  2. The patient was still using dexamethasone at a dose greater than 4 mg/day during mononuclear cell collection;
  3. Patients have a history of autoimmune diseases or other diseases requiring long-term use of hormones or immunosuppressive drugs;
  4. Patients with a history of allergies or allergies to immune cells and adjuvants of cellular products;
  5. Active infection with fever;
  6. Patients with neutropenia (> 10 days) that are difficult to correct after treatment;
  7. Infection with bacteria, fungi or viruses, uncontrolled;
  8. Patients with HIV and those living with active HBV and HCV;
  9. Pregnant, pregnant and lactating women;
  10. Important organ failure (heart, liver, kidney, lung);
  11. 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;
  12. Anything that researchers believe may increase the risk of subjects or interfere with test results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03914768


Locations
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China, Guangdong
Shenzhen Geno-immune Medical Institute
Shenzhen, Guangdong, China, 518000
Department of Neurosurgery, Shenzhen Hospital, Southern Medical University
Shenzhen, Guangdong, China, 518100
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
Investigators
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Principal Investigator: Lung-Ji Chang, PhD Shenzhen Geno-Immune Medical Institute

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Responsible Party: Shenzhen Geno-Immune Medical Institute
ClinicalTrials.gov Identifier: NCT03914768     History of Changes
Other Study ID Numbers: GIMI-IRB-19001
First Posted: April 15, 2019    Key Record Dates
Last Update Posted: July 16, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shenzhen Geno-Immune Medical Institute:
DC vaccine therapy
DIPG
GBM
neoantigen

Additional relevant MeSH terms:
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Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Vaccines
Immunologic Factors
Physiological Effects of Drugs