Protocol summary
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Study aim
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Evaluation the safety of intrathecal injection of activated allogenic NK cells in pediatrics with brain gliomas
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Design
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A phase I, open label, non control, non randomized trial in 10 eligible patients
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Settings and conduct
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Patients will be admitted to Rasoul Akram hospital and in period between end of radiotherapy and start of chemotherapy, or in intervals between chemotherapy courses will receive five injections. Five more injections will be planned in cases of response to the treatment.
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Participants/Inclusion and exclusion criteria
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patients with diagnosis of brain stem glioma, DIPG, unresectable glioma, and relapsed-refractory glioma which have the following inclusion criteria:
1. Age between 3 to 18 years old
2. Hemoglobin level above 10 gr/deciliter of blood
3. Absolute granulocyte count (AGC) above 1500 per microliter of blood
4. Platelet count above 100000 per microliter of blood
5. Lansky/Karnofsky performance score above 60
6. INR below 2 and PTT less than 1/5 times of maximum normal value
7. Plasma Bilirubin level less than 1/5 times of maximum normal value
8. Plasma hepatic transaminases (ALT and AST) level less than 2/5 times of maximum normal value
9. Plasma Creatinine level less than 1/5 times of maximum normal value
the exclusion criteria are:
1.evidence of radio necrosis in MRI or MRS
2. intolerance of new treatment due to emergency condition
3. rupture of cerebral shunt or unable to perform a lumbar puncture (LP)
4. history of other malignancies
5. history of any immunodeficiency diseases or any immune compromising conditions
6. occurrence of new neurologic lesion after first injection
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Intervention groups
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40-50 million activated allogenic NK cells will be injected intrathecally every week till five injection. In cases of response to the treatment, five more injections will be planned
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Main outcome variables
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Safety of intrathecal injection of NK cells
General information
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Reason for update
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20170122032121N6
Registration date:
2021-11-19, 1400/08/28
Registration timing:
registered_while_recruiting
Last update:
2022-10-22, 1401/07/30
Update count:
1
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Registration date
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2021-11-19, 1400/08/28
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2021-10-17, 1400/07/25
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Expected recruitment end date
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2022-10-22, 1401/07/30
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Evaluation of the safety of intrathecal injection of activated allogenic Natural Killer (NK) cells in pediatrics with brain gliomas; A phase I clinical trial
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Public title
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NK cell therapy in pediatrics with brain glioma
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
patients with diagnosis of brain stem glioma, DIPG, unresectable glioma, and relapsed-refractory glioma
Age between 3 to 18 years old
Hemoglobin level above 10 gr/deciliter of blood
Absolute granulocyte count (AGC) above 1500 per microliter of blood
Platelet count above 100000 per microliter of blood
Lansky (for under 16 years old) or Karnofsky (for above 16 years old) performance score above 60
INR below 2 and PTT less than 1/5 times of maximum normal value
Plasma Bilirubin level less than 1/5 times of maximum normal value
Plasma hepatic transaminases (ALT and AST) level less than 2/5 times of maximum normal value
Plasma Creatinine level less than 1/5 times of maximum normal value
Informed consent of parents or legal attendance
Exclusion criteria:
evidence of radio necrosis in MRI or MRS
intolerance of new treatment due to emergency condition
rupture of cerebral shunt or unable to perform a lumbar puncture (LP)
history of other malignancies
history of any immunodeficiency diseases or any immune compromising conditions
occurrence of new neurologic lesion after first injection
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Age
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From 3 years old to 18 years old
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Gender
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Both
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Phase
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1
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Groups that have been masked
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No information
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Sample size
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Target sample size:
10
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Randomization (investigator's opinion)
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N/A
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Randomization description
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Blinding (investigator's opinion)
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Not blinded
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Blinding description
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Placebo
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Not used
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Assignment
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Single
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2021-09-21, 1400/06/30
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Ethics committee reference number
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IR.ACECR.ROYAN.REC.1400.077
Health conditions studied
1
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Description of health condition studied
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Brain glioma
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ICD-10 code
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C71
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ICD-10 code description
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Malignant neoplasm of brain
Primary outcomes
1
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Description
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Safety of intrathecal injection of Natural Killer (NK) cells
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Timepoint
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safety will be measured after each injection till 24 hour in hospital for acute adverse events. Other adverse events will be recorded in periodical follow up in 1, 3, 6, and 12 month after the last injection
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Method of measurement
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Common Terminology Criteria for Adverse Events (CTCAEs) checklist
Secondary outcomes
1
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Description
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Change of tumor size
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Timepoint
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Tumor size will be measured before the first injection and after fifth and tenth injection it will be measured again. 3 month, 6 month and 12 month after the last injection the size will be measured ordinally.
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Method of measurement
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MRI (with and without contrast and DWI method) and MRS
2
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Description
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Overall survival and progression-free survival
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Timepoint
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At the end of the study the survivals will be measured for patients
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Method of measurement
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Kaplan-Meier method
3
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Description
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Cerebrospinal fluid (CSF) analysis (cytokine changes, hematology, and biochemistry)
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Timepoint
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Before each injection, samples of CSF will be taken and will sent to lab for analysis
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Method of measurement
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ELISA, Spectrophotometry, microscopic study
Intervention groups
1
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Description
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Intervention group: 40-50 million activated allogenic NK cells will be injected intrathecally every week till five injection. In cases of response to the treatment, five more injections will be planned.
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Category
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Treatment - Other
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Royan institute
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Proportion provided by this source
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10
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
2
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Kian Immune Cell company
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Proportion provided by this source
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90
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Yes - There is a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Not applicable
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Title and more details about the data/document
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After concealment of personal information of participants, data of eligibility, CRFs and measured outcomes can be shared in case of request.
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When the data will become available and for how long
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After publishing results in a scientific journal with no deadline
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To whom data/document is available
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Just to academic PIs
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Under which criteria data/document could be used
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Any usage of data should be consulted and approved by the PIs (Dr.Ebrahimi and Dr.Faranoush)
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From where data/document is obtainable
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Applicant should send an e-mail to Dr.Mahdizadeh and propose their detailed requirements of the study data
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What processes are involved for a request to access data/document
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After sending an e-mail to Dr.Mahdizadeh, he will assess the authenticity of the applicant in almost 2 weeks. Then he will plan a meeting (visual or attendance) for the applicant with Dr.Ebrahimi and Dr.Faranoush in next month. The applicant can obtain approval of data sharing in this meeting and the data will be sent in next 14 days.
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Comments
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