Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle to Treatment of Glioblastoma: Safety and Feasibility Assessment
Evaluation of safety and feasibility of using bone marrow mesenchymal stem cells containing lentivirus carrying thymidine kinase gene in patients with glioblastoma multiforme.
Design
Uncontrolled phase 1 clinical trial in 5 patients.
Settings and conduct
Five patients with glioblastoma confirmed by two pathologists will be examined in this study. This study does not have a control group and randomization. Patients will be examined every three months until tumor recurrence and death. The study site will be Shohadaye Tajrish Hospital.
Participants/Inclusion and exclusion criteria
Inclusion criteria:
Karnofsky performance status> 70.
Adequate hematological function (an absolute neutrophil count > 1500/μl and platelet count > 125000/mm3).
Adequate renal function (creatinine < 1.5 times the normal).
Adequate hepatic function (aspartate aminotransferase and bilirubin < 1.5 times the normal).
Patients who fill informed consent.
Exclusion criteria:
Significant vascular disease.
History of recurrent thromboembolism.
Prior history of hypertensive crisis or hypertensive encephalopathy.
Gastrointestinal fistula or perforation.
History of an intraabdominal or intracranial abscess within 6 months.
Serious non-healing wound, ulcer and bone fracture.
Intervention groups
Intervention group: This group undergoes gene therapy along with standard treatment (chemotherapy and radiotherapy). From this group of patients, bone marrow stem cells are isolated and brain tumor resection is performed on them. Then 5×10^5 mesenchymal stem cells infected with lentivirus carrying the Thymidine Kinase gene are injected into the evacuated tumor site under the guidance of a brain navigation device. After cell injection, the Ganciclovir drug administration continues for a total of 28 doses over 14 days.
Main outcome variables
Overall survival; progression-free survival.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200502047277N2
Registration date:2020-10-08, 1399/07/17
Registration timing:retrospective
Last update:2020-10-08, 1399/07/17
Update count:1
Registration date
2020-10-08, 1399/07/17
Registrant information
Name
saeed oraee yazdani
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 25719
Email address
saeed_o_yazdani@sbmu.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2017-12-11, 1396/09/20
Expected recruitment end date
2020-09-05, 1399/06/15
Actual recruitment start date
2018-02-04, 1396/11/15
Actual recruitment end date
2020-09-05, 1399/06/15
Trial completion date
2020-09-05, 1399/06/15
Scientific title
Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle to Treatment of Glioblastoma: Safety and Feasibility Assessment
Public title
Evaluation of the safety and feasibility of stem cell-mediated gene therapy in the treatment of glioblastoma
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Karnofsky performance status> 70.
Adequate hematological function (an absolute neutrophil count > 1500/μl and platelet count > 125000/mm3).
Adequate renal function (creatinine < 1.5 times the normal).
Adequate hepatic function (aspartate aminotransferase and bilirubin < 1.5 times the normal).
Patient who fill informed consent.
Exclusion criteria:
Significant vascular disease.
History of recurrent thromboembolism.
Prior history of hypertensive crisis or hypertensive encephalopathy.
Gastrointestinal fistula or perforation.
History of intraabdominal or intracranial abscess within 6 months.
Serious non healing wound, ulcer and bone fracture.
Age
No age limit
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size:
8
Actual sample size reached:
5
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Shahid Beheshti University of Medical Sciences
Street address
Shohadaye tajrish hospital, Tajrish Avenue
City
Tehran
Province
Tehran
Postal code
1989934148
Approval date
2017-06-07, 1396/03/17
Ethics committee reference number
IR.SBMU.REC.1396.224
Health conditions studied
1
Description of health condition studied
Glioma grade 4
ICD-10 code
C71
ICD-10 code description
Malignant neoplasm of brain
Primary outcomes
1
Description
Overall survival (OS) of patients
Timepoint
Before treatment and every three months until the patient's death
Method of measurement
The time from treatment initiation until patient's death
2
Description
Radiological progression free survival (PFS) of patients
Timepoint
Before treatment and every three months until the disease recurrence
Method of measurement
The time from treatment initiation until disease progression or worsening
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: This group undergoes gene therapy along with standard treatment (chemotherapy and radiotherapy). From this group of patients, bone marrow stem cells are isolated and brain tumor resection is performed on them. Then 5×10^5 mesenchymal stem cells infected with lentivirus carrying the Thymidine Kinase gene are injected into the evacuated tumor site under the guidance of a brain navigation device. After cell injection, the Ganciclovir drug administration continues for a total of 28 doses over 14 days.