The safety and efficiency evaluation of allogenic Natural Killer cell therapy in relapsed Neuroblastoma pediatric patients post hematopoietic stem cell transplantation: Phase I clinical study
Launching a new cell therapy method for children with recurrent neuroblastoma after hematopoietic stem cell transplantation
Evaluation of tolerability, complications, or immunity of NK cells in children with neuroblastoma for Disease-Free survival
Design
Open-label, one arm non-randomized trial of 5 patients
Settings and conduct
Administration of NK cells at a dose of 10 million per kilogram of body weight intravenously at the first time and if the dose is tolerated then administration of 50 million/kg three weeks later by a therapist at the Pediatric Cell Therapy Research Center.
Participants/Inclusion and exclusion criteria
Inclusion criteria:
Recurrent neuroblastoma after receiving hematopoietic stem cell transplant with the following criteria:
1) Any amount of neuroblastoma tumor cells in the bone marrow that can be seen from at least one aspiration sample
2) Tumors seen on CT in at least one soft tissue.
3) Have at least 1 MIBG-lesion with a score of 1-2 Curie
4) The patient has a life expectancy of at least 12 weeks. Lansky (under 16 years old) or Karnowski (over 16 years old) score 50.
5) The function of the patient organs must be acceptable. The hematologic function must be as follows:
A. Absolute Phagocyte count (APC= neutrophils and monocytes): ≥ 1000/µL
B. Absolute Neutrophil count: ≥750/µL
C. Absolute Lymphocyte count ≥ 500/µL
6) Patient age from 1 to 15 years
Exclusion criteria:
Active or uncontrollable infection
History of allergies or any sensitivity to animal proteins
Heat failure
Serious mental and physical disabilities
Participation in any other clinical trial
Intervention groups
Administration of NK cells at doses of 10 and 50 million per kg of body weight without a control group
Main outcome variables
Tolerance, any complications or immunity of NK cells in children with neuroblastoma in terms of Disease-Free Survival
General information
Reason for update
Acronym
NKNB
IRCT registration information
IRCT registration number:IRCT20201202049568N1
Registration date:2021-02-20, 1399/12/02
Registration timing:registered_while_recruiting
Last update:2021-02-20, 1399/12/02
Update count:0
Registration date
2021-02-20, 1399/12/02
Registrant information
Name
Rashin Mohseni
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 6694 8444
Email address
rashin_mohseni@yahoo.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-02-19, 1399/12/01
Expected recruitment end date
2022-02-20, 1400/12/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The safety and efficiency evaluation of allogenic Natural Killer cell therapy in relapsed Neuroblastoma pediatric patients post hematopoietic stem cell transplantation: Phase I clinical study
Public title
Allogenic Natural Killer cell therapy in relapsed Neuroblastoma pediatric patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Any amount of neuroblastoma tumor cells in the bone marrow that can be seen from at least one aspiration sample
Tumors seen on CT in at least one soft tissue.
Have at least 1 MIBG- lesion with a score of 1-2 Curie
The patient has a life expectancy of at least 12 weeks.
The function of the patients organs must be acceptable.
Patient age from 1 to 15 years
Exclusion criteria:
Active or uncontrollable infection
History of allergies or any hypersensitivity to animal proteins
Heart failure
Serious mental and physical disabilities
Participation in any other clinical trial
Age
From 1 year old to 15 years old
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size:
5
Randomization (investigator's opinion)
Not randomized
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 Tehran University of Medical Sciences
Street address
Pediatric Cell Therapy Research Center, Keshavarz Blvd, Dr Gharib St.
City
Tehran
Province
Tehran
Postal code
1419733151
Approval date
2020-11-21, 1399/09/01
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1399.817
Health conditions studied
1
Description of health condition studied
Neuroblastoma
ICD-10 code
C74.90
ICD-10 code description
Malignant neoplasm of unspecified part of unspecified adrenal gland
Primary outcomes
1
Description
To measure tumor response after infusion of expanded activated NK cells. Response will be assessed as defined by Revised International Neuroblastoma Response Criteria 2017.
Timepoint
Each 6 month Over 2 years
Method of measurement
Disease status at primary and metastatic soft tissue sites will be assessed using MIBG scans or PET scan as applicable.
Secondary outcomes
1
Description
To measure the numbers of infused NK cells in peripheral blood at specific time-points after NK cell infusion
Timepoint
before intervention and 2, 4 , 6 month after intervention
Method of measurement
NK cells will be identified by flow cytometry in peripheral blood and their percentages and absolute numbers will be calculated.
Intervention groups
1
Description
Intervention group: NK cells that were isolated by CliniMACS from apheresis samples will be expanded over 10 days in a specific media with 10% serum and will be infused in combination with cyclophosphamide 60mg/kg on day -3 and day -2 prior to the NK cell infusion.NK cells will be injected intravenously at doses of 10 million and 50 million per kilogram of body weight at three-week intervals.
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Pediatric Cell Therapy Research Center
Full name of responsible person
Amir Ali Hamidieh
Street address
Children's Medical Center Hospital, Gharib St., Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 21 6740 9000
Email
aahamidieh@tums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Amir Ali Hamidieh
Street address
Gharib St., Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 21 6147 9000
Email
aahamidieh@tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
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
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Rashin Mohseni
Position
Consultant
Latest degree
Ph.D.
Other areas of specialty/work
Cell Therapy
Street address
Gharib St., Keshavarz Blvd,
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 21 6147 9000
Email
rashin_mohseni@yahoo.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Rashin Mohseni
Position
Assistant Professor
Latest degree
Ph.D.
Other areas of specialty/work
Cell Therapy and Regenerative Medicine
Street address
Pediatric Cell Therapy Research Center, Children's Medical Center Hospital, Gharib Ave, Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 21 6694 8444
Fax
Email
rashin_mohseni@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Rashin Mohseni
Position
Assistant Professor
Latest degree
Ph.D.
Other areas of specialty/work
Cell Therapy and Regenerative Medicine
Street address
Pediatric Cell Therapy Research Center, Children's Medical Center Hospital, Gharib Ave, Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 21 6694 8444
Fax
Email
rashin_mohseni@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
Not applicable
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
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
All collected deidentified IPD will be shared.
When the data will become available and for how long
January 2023
To whom data/document is available
academic institutions and hospitals
Under which criteria data/document could be used
No limitation
From where data/document is obtainable
Rashin Mohseni
rashin_mohseni@yahoo.com
What processes are involved for a request to access data/document