A Triple-blind Randomized Clinical Study of Vaccination With Dendritic Cells Loaded With Glioma Stem-like Cells Associated Antigens Against Brain Glioblastoma Multiform
18 Years
70 Years
Both
Glioma, Glioblastoma Multiforme, Neoplasms
Trial Information
A Triple-blind Randomized Clinical Study of Vaccination With Dendritic Cells Loaded With Glioma Stem-like Cells Associated Antigens Against Brain Glioblastoma Multiform
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 [1], 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 [2].
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.
Inclusion Criteria:
1. Patients with histologically confirmed brain glioblastoma multiforme.
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.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Description:
To determine time to death in the enrolled patients.
Outcome Time Frame:
within 2 years after the surgery
Safety Issue:
No
Principal Investigator
Liangfu Zhou, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
Huashan Hospital, Fudan University
Authority:
China: Food and Drug Administration
Study ID:
DC81001115
NCT ID:
NCT01567202
Start Date:
March 2012
Completion Date:
July 2014
Related Keywords:
- Glioma
- Glioblastoma Multiforme
- Neoplasms
- Brain tumor
- Glioma
- Glioblastoma
- Tumor stem cells
- Immunotherapy
- Vaccine
- Neoplasms
- Glioblastoma
- Glioma
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