The Safety Evaluation of Ex vivo Activated Haploidentical Natural Killer Cells (NK) in children with recurrent Glioblastoma Multiform (a phase I clinical trial)
The Safety Evaluation of Ex vivo Activated Natural Killer Cells (NK) for tumor-targeting in Recurrent Glioblastoma Multiform patients
Design
Five children with recurrent glioblastoma and one parent for each patient will be selected by a clinical trial team and will enter the Phase 1 single-group clinical trial study.
Settings and conduct
Workplace: Royan Institute
Study process: 1- Blood sampling and isolation of mononuclear cells (from sick patients)
2- Isolation of CD56 + cells
3- Activation of cells by IL2 and HSP70
4- Assessment of lethality and surface marker of NK cells
5- Evaluation of sterility tests in activated cells
6- Preparing patients
7- Cell injection into the tumor cavity before radiotherapy or chemotherapy
8- Safety analysis of the method after injection
Participants/Inclusion and exclusion criteria
Inclusion criteria: children with recurrent Glioblastoma Multiform (GBM),
being at the age of 3-12 Year,
both sexes,
Lansky performance statue of 70-100%,
Life span expectation > 6 months. Non-inclusion criteria: Patients whose MRI or MRS view of the brain is in favor of radio necrosis,
the patient can’t tolerate the new treatment due to emergency conditions,
Insufficient number of NK cells produced for treatment,
appearance new neurological ulcers after the first injection
Intervention groups
Intervention process: 1- selection of 5 patients and their haploidentical donor;
2- peripheral blood collection, isolation the CD56+ cells and cell activation with IL-2/Hsp70;
3- Doing control quality tests before cell injection;
4-Injection in the tumor cavity.
Main outcome variables
Fever, hysteria, new neurological symptoms, tumor size
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20170122032121N5
Registration date:2020-06-11, 1399/03/22
Registration timing:prospective
Last update:2020-06-11, 1399/03/22
Update count:1
Registration date
2020-06-11, 1399/03/22
Registrant information
Name
Marzieh Ebrahimi
Name of organization / entity
Royan Institute
Country
Iran (Islamic Republic of)
Phone
+98 23562516
Email address
mebrahimi@royaninstitute.org
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-07-10, 1399/04/20
Expected recruitment end date
2021-07-23, 1400/05/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The Safety Evaluation of Ex vivo Activated Haploidentical Natural Killer Cells (NK) in children with recurrent Glioblastoma Multiform (a phase I clinical trial)
Public title
Nk cell therapy for recurrent GBM (Glioblastoma Multiform)
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age: 3-12 Year
Sex: Both
Lansky performance statue: 70-100%
Life span expectation: >6 months
Hemoglobin: > 10.0 g/dL
AGC > 1,500/mm³
Platelet count > 100,000/mm³
Serum total bilirubin < 1.5 times upper limit of normal(ULN)
ALT and AST < 2.5 times ULN
Serum creatinine < 1.5 times ULN
Exclusion criteria:
Patients whose MRI or MRS view of the brain is in favor of radio necrosis
Due to emergency conditions, the patient can not tolerate the new treatment
Insufficient number of NK cells produced for treatment
appearance new neurological ulcers after the first injection (after the wound heals, subsequent injections will be given if the patient is in good condition)
diagnosis of any other invasive cancer within the past 5 years.
Closing the reservare for the next injection (if this problem is solved, the injections will be done again.
concurrent serious medical or psychiatric illness that may interfere with giving informed consent or conducting this study
Age
From 3 years old to 12 years old
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size:
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 the Royan Institute
Street address
ٌRoyan institute, Royan alley, Banihashem street, Resalat High Way
City
Tehran
Province
Tehran
Postal code
1665659911
Approval date
2020-02-29, 1398/12/10
Ethics committee reference number
IR.ACECR.ROYAN.REC.1398.261
Health conditions studied
1
Description of health condition studied
Recurrent Glioblastoma Multiform(GBM)
ICD-10 code
C71.9
ICD-10 code description
Malignant neoplasm of brain, unspecified
Primary outcomes
1
Description
fever
Timepoint
After cell injection, every 2 hours up to 48 hours after cell injection
Method of measurement
Fever meter
2
Description
hysteria
Timepoint
After cell injection, control the symptom up to 48 hours.
Method of measurement
Patient checkup
3
Description
New neurological symptoms which not related to the tumor
Timepoint
Up to 48 hours after surgery, up to one week after cell injection
Method of measurement
Physical examination and recording of symptoms
Secondary outcomes
1
Description
Tumor size
Timepoint
One week after injection, every 2 weeks up to 3 months
Method of measurement
MRI and MRS
2
Description
patient's survival
Timepoint
Every month up to 6 months
Method of measurement
Communicate with patients
Intervention groups
1
Description
Intervention group: 5 children with recurrent glioblastoma are included in the study according to the inclusion criteria. The peripheral blood of one parent is obtained with his/her consent. Then the NK cells are isolated and activated by the cliniMACS device. Microbial tests and cell quality control are performed. 7 days after surgery, MRI is ordered then, two million cells per 0.5 cc are injected into the tumor cavity removed by surgery via a reservare which fixes in the patient's cranium. This injection is given again in the second and third weeks after the surgery and before the start of radiotherapy.
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Children's Medical Center
Full name of responsible person
Dr.Marzieh Ebrahimi
Street address
Royan Institute, Masoud alley, Banihashem square, Resalat Highway, Tehran.
City
Tehran
Province
Tehran
Postal code
1665659911
Phone
+98 21 2356 2516
Fax
+98 21 2356 2507
Email
marzieh.ebrahimi@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Dr. Parvaneh Afsharian
Street address
Royan Institute, Royan alley, Banihashem square, Resalat Highway, Tehran
City
Tehran
Province
Tehran
Postal code
1665659911
Phone
+98 21 2356 2674
Fax
+98 21 2356 2677
Email
pafshar@royaninstitute.org
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Iranian academic center for education culture and research
Proportion provided by this source
25
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
2
Sponsor
Name of organization / entity
Parsian Lotus Investment Bank
Full name of responsible person
Mojtaba jahangiri
Street address
No.99, Mehran dead end alley, Sheikh bahaei street, Mollasadra street, Tehran
City
Tehran
Province
Tehran
Postal code
1991781988
Phone
+98 21 8656
Email
info@lotusib.ir
Web page address
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Parsian Lotus Investment Bank
Proportion provided by this source
75
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
Person responsible for general inquiries
Contact
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Niloufar Shayan Asl
Position
Research assistant
Latest degree
Master
Other areas of specialty/work
Others
Street address
Royan Institute ,Royan alley, Banihashem square, Resalat highway, Tehran.
City
Tehran
Province
Tehran
Postal code
1665659911
Phone
+98 21 2356 2521
Email
niloufar.shayanasl@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Dr.Marzieh Ebrahimi
Position
Associated professor
Latest degree
Ph.D.
Other areas of specialty/work
Immunology
Street address
Royan Institute ,Royan alley, Banihashem square, Resalat highway, Tehran.
City
Tehran
Province
Tehran
Postal code
1665659911
Phone
+98 21 2356 2516
Email
marzieh.ebrahimi@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Niloufar Shayan Asl
Position
Research assistant
Latest degree
Master
Other areas of specialty/work
Others
Street address
Royan Institute ,Royan alley, Banihashem square, Resalat highway, Tehran.
City
Tehran
Province
Tehran
Postal code
1665659911
Phone
+98 21 2356 2521
Email
niloufar.shayanasl@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Yes - There is a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
The research results with the publication of the article will be provided to researchers.
When the data will become available and for how long
-
To whom data/document is available
-
Under which criteria data/document could be used
-
From where data/document is obtainable
-
What processes are involved for a request to access data/document