Study of DC Vaccination Against Glioblastoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Huashan Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Fudan University
Information provided by (Responsible Party):
Jinsong Wu, Huashan Hospital
ClinicalTrials.gov Identifier:
NCT01567202
First received: March 26, 2012
Last updated: March 28, 2012
Last verified: March 2012

March 26, 2012
March 28, 2012
March 2012
January 2014   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: within 2 years after the surgery ] [ Designated as safety issue: No ]
To determine time to death in the enrolled patients.
Same as current
Complete list of historical versions of study NCT01567202 on ClinicalTrials.gov Archive Site
Progression free survival [ Time Frame: Every 4 weeks from baseline to 6 months ] [ Designated as safety issue: No ]
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.
Same as current
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 [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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.
    Interventions:
    • 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.
    Interventions:
    • Procedure: Surgery
    • Drug: Chemotherapy
    • Radiation: Radiotherapy
    • Drug: blank placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
July 2014
January 2014   (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.
Both
18 Years to 70 Years
No
Contact: Liangfu Zhou, M.D. 86-21-52889999-7206 lfzhouc@126.com
Contact: Wei Hua, M.D., Ph.D. 15800589540 doctor.huawei@gmail.com
China
 
NCT01567202
DC81001115
Yes
Jinsong Wu, Huashan Hospital
Huashan Hospital
Fudan University
Principal Investigator: Liangfu Zhou, M.D. Huashan Hospital, Fudan University
Huashan Hospital
March 2012

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