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Study of DC Vaccination Against Glioblastoma

This study is currently recruiting participants.
Verified March 2012 by Huashan Hospital
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
History of Changes
  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).


Condition Intervention Phase
Glioma
Glioblastoma Multiforme
Neoplasms
 Procedure: Surgery
Drug: Chemotherapy
Radiation: Radiotherapy
Biological: DC vaccination
Drug: blank placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Huashan Hospital:

Primary Outcome Measures:
  • Overall survival [ Time Frame: within 2 years after the surgery ] [ Designated as safety issue: No ]
    To determine time to death in the enrolled patients.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 100
Study Start Date: March 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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.
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
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.
Drug: blank placebo
Saline that has the same appearance with DC vaccine.

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 [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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01567202

Contacts
Contact: Liangfu Zhou, M.D. 86-21-52889999-7206 lfzhouc@126.com
Contact: Wei Hua, M.D., Ph.D. 15800589540 doctor.huawei@gmail.com

Locations
China, Shanghai
Huashan hospital, Fudan university Recruiting
Shanghai, Shanghai, China, 200040
Contact: Liangfu Zhou, M.D.     86-21-52889999-7206     lfzhouc@126.com    
Contact: Wei Hua, M.D.,Ph.D.     15800589540     doctor.huawei@gmail.com    
Principal Investigator: Liangfu Zhou, M.D.            
Sub-Investigator: Yiwei Chu, M.D.,Ph.D.            
Sponsors and Collaborators
Huashan Hospital
Fudan University
Investigators
Principal Investigator: Liangfu Zhou, M.D. Huashan Hospital, Fudan University
  More Information

Publications:

Responsible Party: Jinsong Wu, M.D., Ph.D., Huashan Hospital
ClinicalTrials.gov Identifier: NCT01567202     History of Changes
Other Study ID Numbers: DC81001115
Study First Received: March 26, 2012
Last Updated: March 28, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Huashan Hospital:
Brain tumor
Glioma
Glioblastoma
 Tumor stem cells
Immunotherapy
Vaccine

Additional relevant MeSH terms:
Neoplasms
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
 Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on June 18, 2013