Clinical Trials /

Study of DC Vaccination Against Glioblastoma

NCT01567202

Description:

This is a Phase II study in a single center to determine the efficacy of autologous dendritic cells (DCs) loaded with autogeneic glioma stem-like cells (A2B5+) administered as a vaccination in adults with glioblastoma multiforme (primary or secondary).

Related Conditions:
  • Glioblastoma
  • Glioblastoma, IDH-Wildtype
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of DC Vaccination Against Glioblastoma
  • Official Title: A Triple-blind Randomized Clinical Study of Vaccination With Dendritic Cells Loaded With Glioma Stem-like Cells Associated Antigens Against Brain Glioblastoma Multiform

Clinical Trial IDs

  • ORG STUDY ID: DC81001115
  • NCT ID: NCT01567202

Conditions

  • Glioma
  • Glioblastoma Multiforme
  • Neoplasms

Interventions

DrugSynonymsArms
ChemotherapyArm DC
DC vaccinationArm DC
blank placeboArm Placebo

Purpose

This is a Phase II study in a single center to determine the efficacy of autologous dendritic cells (DCs) loaded with autogeneic glioma stem-like cells (A2B5+) administered as a vaccination in adults with glioblastoma multiforme (primary or secondary).

Detailed Description

      Despite the advances in diagnosis and treatment (surgery +radiation +chemotherapy), median
      survival for patients with newly diagnosed brain glioblastoma multiform (GBM) is about one
      year, for recurrent GBM is about 4 months. Recently, immunotherapy has emerged as a novel
      treatment strategy for glioma with improving patient survival. Usually, processed tumor
      antigens from the patient's own tumor or a peptide vaccine is capable of producing an
      anti-glioma response. Our previous experiment revealed that the CD133+ tumor stem-like cells
      associated antigens could elicit highly intensive immune response against human malignant
      glioma , and in phase I study, we have confirmed that DC vaccine loaded with glioma stem-like
      cells associated antigens against malignant glioma in recurrent patients was of safety .

      Autologous DCs will be obtained from peripheral blood mononuclear cells (PBMCs) from each
      patient. Stem-like cells associated antigens (SAA) will be prepared with glioma stem-like
      cells that are harvested from patients with GBM and primary cultured and sorted
      flowcytometrically and then irradiated. Approximately 4 weeks will be required for vaccine
      production and the first vaccine administration. Each patient will receive an injection of
      DCs at his/her assigned dose once every week during the first 6 week. The dose of DCs is
      defined as 8~10×10^6.

      Clinical trials that utilize DCs for immunotherapy have demonstrated significant survival
      benefit for patients who exhibit robust immune responses against tumor cells. Unfortunately,
      at the present time the majority of clinical trials were in phase I that illustrated the
      safety. The efficacy of DCs against glioblastoma is still lack of sufficient randomized phase
      II study. According to our previous phase I study, here we designed this clinical trial in a
      triple-blind randomized manner to validate the efficacy of DCs vaccination.

      Recently,an exploratory randomized phase II clinical trial have been completed (Cancer
      immunology &immunotheapy ,2018,1677,1677-1688 ; PubMed ID: 30159779), 43 GBM patients were
      randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline
      placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed.
      Participants were stratified into different molecular subgroups based on the mutation (MT)
      status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT).
      Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory
      molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed
      that DCV treatment significantly prolonged OS (p = 0.02) after adjusting for IDH1 and TERT
      promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1wild type (WT) TERTMT
      patients, DCV treatment significantly prolonged OS (p < 0.01) and PFS (p = 0.03) and
      increased plasma levels of cytokines CCL22 and IFN-γ compared with placebo. Patients with low
      B7-H4 expression showed significantly prolonged OS (p = 0.02) after DCV treatment.

      In the present study, IDH1WTTERTMT subgroups of GBM patients more responsive to GSC DCV-based
      specific active-immunotherapy. However,It is noted that IDH1WTTERTMTGBM patients was analysed
      in a cohort samples which are not randomlized and the present study population is too small
      to evaluate conclusively demographic criteria for entry and patient recruitment. the results
      of the present study should be confirmed in a random cohort of IDH1WTTERTMT GBM patients.
      Accordingly , we made some modifications to the original plan, and are currently recruiting
      new participants.
    

Trial Arms

NameTypeDescriptionInterventions
Arm DCExperimentalIn this arm, the patients will receive DC vaccination in addition to the standard therapy, including Surgery, Chemotherapy, and Radiotherapy.
  • Chemotherapy
  • DC vaccination
Arm PlaceboPlacebo ComparatorIn this arm, the patients will receive blank placebo instead of the DC vaccination in addition to the standard therapy.
  • Chemotherapy
  • blank placebo

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with histologically confirmed brain glioblastoma multiforme and molecular
             subgroups of IDH1 wildtype TERT mutation。

          2. Patients with maximum safe resection of the tumor (≥95%) confirmed with contrast MR
             within 72 hours after surgery.

          3. Age from 18 through 70 years.

          4. Karnofsky performance score of ≥ 60%.

          5. Adequate organ function within 14 days of study registration including the following:

             Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count, (ANC) ≥
             1.0×10^9/L, platelets ≥100×10^9/L; hemoglobin ≥ 9 g/dL. Hepatic: bilirubin ≤1.3 mg/dL
             or 0-22 mmol/L, aspartate transaminase (AST) and alanine transaminase (ALT) < 3×upper
             limit of normal (ULN). Renal: Normal serum Creatinine for age (below) or creatinine
             clearance >60 ml/min/1.73 m^2. Electrocardiogram: normal.

          6. Written informed consent must be obtained from all patients, with the understanding
             that consent may be withdrawn by the subject at any time without prejudice to future
             medical care.

        Exclusion Criteria:

          1. Pregnant or breast-feeding patients. Pregnancy testing will be performed on all
             menstruating females within 14 days of study enrollment.

          2. Patients with uncontrolled intercurrent illness including, but not limited to ongoing
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,
             or psychiatric illness/social situations that would limit compliance with study
             requirements.

          3. Patients with history of immune system abnormalities such as hyperimmunity (e.g.,
             autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow
             failures, AIDS, ongoing pregnancy, transplant immuno-suppression), or medication of
             cortisol.

          4. Patients with any conditions that could potentially alter immune function (e.g., AIDS,
             multiple sclerosis, diabetes, renal failure).

          5. Patients currently received any other investigational agents.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) of the treatment using DC Vaccination for Glioblastoma with molecular markers for immunotherapy.
Time Frame:Every 4 weeks from baseline to 6 months.
Safety Issue:
Description:The objective response rate (ORR) is defined as the proportion of patients who achieve radiographic partial or complete response (PR or CR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guideline.Molecular markers are based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT).

Secondary Outcome Measures

Measure:Progression free survival
Time Frame:Every 4 weeks from baseline to 6 months.
Safety Issue:
Description:Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.
Measure:Overall survival
Time Frame:within 2 years after the surgery
Safety Issue:
Description:Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Huashan Hospital

Trial Keywords

  • Brain tumor
  • Glioma
  • Glioblastoma
  • Tumor stem cells
  • Immunotherapy
  • Vaccine

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