Study of DC Vaccination Against Glioblastoma

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. Identifier: NCT01567202
Recruitment Status : Unknown
Verified May 2015 by Jinsong Wu, Huashan Hospital.
Recruitment status was:  Recruiting
First Posted : March 30, 2012
Last Update Posted : May 20, 2015
Fudan University
Information provided by (Responsible Party):
Jinsong Wu, Huashan Hospital

March 26, 2012
March 30, 2012
May 20, 2015
March 2012
December 2016   (Final data collection date for primary outcome measure)
Overall survival [ Time Frame: within 2 years after the surgery ]
To determine time to death in the enrolled patients.
Same as current
Complete list of historical versions of study NCT01567202 on Archive Site
  • Progression free survival [ Time Frame: Every 4 weeks from baseline to 6 months ]
    To determine time to tumor progression in this patient population -exhibit a prolonged time to tumor progression by the absence of tumor growth as determined by MRI.
  • To correlate and characterize the immune response to the clinical response [ Time Frame: within 2 years after the surgery ]
  • To explore the association of GBM molecular subtype with immune response [ Time Frame: within 2 years after the surgery ]
  • To evaluate the effect of residual tumor volume on the immune response. [ Time Frame: within 2 years after the surgery ]
Progression free survival [ Time Frame: Every 4 weeks from baseline to 6 months ]
To determine time to tumor progression in this patient population -exhibit a prolonged time to tumor progression by the absence of tumor growth as determined by MRI.
Not Provided
Not Provided
Study of DC Vaccination Against Glioblastoma
A Triple-blind Randomized Clinical Study of Vaccination With Dendritic Cells Loaded With Glioma Stem-like Cells Associated Antigens Against Brain Glioblastoma Multiform
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).

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 , in order to re-estimate sample size and examine the efficacy of the DC vaccine . the interim analysis was performed by an independent data monitoring committee , this analysis contained: 11 cases in the placebo group and 11 cases in the control group. According to interim results : 86% of patients had achieved its primary endpoint events with minimal adverse events. However , our preliminary data is too unreliable to conclude anything further about the effency of DC vaccine: some variability need to be included in the analysis and balanced between two groups , such as the immune response, residual tumor volume, the molecular subtype of GBM . Accordingly , we made some modifications to the original plan, and are currently recruiting new participants.

Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Glioma
  • Glioblastoma Multiforme
  • Neoplasms
  • Procedure: Surgery
    Maximum resection of the tumor (≥95%) with the help of conventional or intraoperative MRI neuronavigation. Confirmation will be proceeded by the contrast MRI within 72 hours after surgery.
  • Drug: Chemotherapy
    Temozolomide(TMZ), 200mg·m^-2·d ×5 days,28 days every cycle. 6 cycles of TMZ are recommended.
  • Radiation: Radiotherapy
    Standard dose, 4500 cGy to tumor with 3-cm margins, 1500 cGy boost to tumor bed.
  • Biological: DC vaccination
    Eight to ten million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.
  • Drug: blank placebo
    Saline that has the same appearance with DC vaccine.
  • Experimental: Arm DC
    In this arm, the patients will receive DC vaccination in addition to the standard therapy, including Surgery, Chemotherapy, and Radiotherapy.
    • Procedure: Surgery
    • Drug: Chemotherapy
    • Radiation: Radiotherapy
    • Biological: DC vaccination
  • Placebo Comparator: Arm Placebo
    In this arm, the patients will receive blank placebo instead of the DC vaccination in addition to the standard therapy.
    • Procedure: Surgery
    • Drug: Chemotherapy
    • Radiation: Radiotherapy
    • Drug: blank placebo

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Unknown status
December 2016
December 2016   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Not Provided
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Jinsong Wu, Huashan Hospital
Huashan Hospital
Fudan University
Principal Investigator: Liangfu Zhou, M.D. Huashan Hospital
Huashan Hospital
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP