Protocol summary
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Study aim
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The Safety Evaluation of Ex vivo Activated Natural Killer Cells (NK) for tumor-targeting inpatient with Recurrent Glioblastoma Multiform and resistant/recurrent malignant brain tumor
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Design
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Five patients with recurrent glioblastoma or malignant brain tumor and one haploidentical donor for each patient will be selected by a clinical trial team and will enter the Phase 1 single-group clinical trial study.
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Settings and conduct
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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 IL-15
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
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Participants/Inclusion and exclusion criteria
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Inclusion criteria: patients with recurrent Glioblastoma Multiform (GBM) or brain tumor,
being at the age of 3-65 Year,
both sexes,
Lansky/karnofsky 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 radionecrosis,
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
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Intervention groups
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Intervention process: 1- selection of 5 patients and their haploidentical donor;
2- peripheral blood collection, isolation of the CD56+ cells and cell activation with IL-15;
3- Doing control quality tests before cell injection;
4-Injection in the tumor cavity or CSF.
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Main outcome variables
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Fever, hysteria, new neurological symptoms, tumor size
General information
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Reason for update
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Because we realized at the beginning of the study that adult patients could also be included in the study and that the cell could be injected into the cerebrospinal fluid. According to studies to activate killer cells, only interleukin-15 could be examined.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20170122032121N5
Registration date:
2020-06-11, 1399/03/22
Registration timing:
prospective
Last update:
2021-06-21, 1400/03/31
Update count:
1
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Registration date
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2020-06-11, 1399/03/22
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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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2020-07-10, 1399/04/20
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Expected recruitment end date
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2021-07-23, 1400/05/01
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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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: The Safety Evaluation of Ex vivo Activated Haploidentical Natural Killer Cells (NK) in patients with Recurrent Glioblastoma Multiform and resistant/recurrent malignant brain tumor (Clinical Trial Phase I)
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Public title
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Nk cell therapy for recurrent GBM (Glioblastoma Multiform)
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Age: 3-65 Year
Sex: Both
Lansky/Karnofsky performance statue: 7-100%
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
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Age
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From 3 years old to 65 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:
5
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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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2020-02-29, 1398/12/10
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Ethics committee reference number
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IR.ACECR.ROYAN.REC.1398.261
2
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Ethics committee
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Approval date
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2021-02-17, 1399/11/29
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Ethics committee reference number
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IR.ACECR.ROYAN.REC.1398.261
Health conditions studied
1
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Description of health condition studied
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Recurrent Glioblastoma Multiform(GBM) and resistant/recurrent malignant brain tumor
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ICD-10 code
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C71.9
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ICD-10 code description
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Malignant neoplasm of brain, unspecified
Primary outcomes
1
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Description
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fever
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Timepoint
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After cell injection, every 2 hours up to 48 hours after cell injection
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Method of measurement
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Fever meter
2
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Description
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hysteria
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Timepoint
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After cell injection, control the symptom up to 48 hours.
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Method of measurement
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Patient checkup
3
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Description
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New neurological symptoms which not related to the tumor
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Timepoint
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Up to 48 hours after surgery, up to one week after cell injection
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Method of measurement
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Physical examination and recording of symptoms
Secondary outcomes
1
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Description
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Tumor size
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Timepoint
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One week after injection, every 2 weeks up to 3 months
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Method of measurement
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MRI and MRS
2
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Description
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patient's survival
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Timepoint
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Every month up to 6 months
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Method of measurement
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Communicate with patients
Intervention groups
1
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Description
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Intervention group: 5 patients with recurrent glioblastoma and resistant/recurrent malignant brain tumor 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 (cell count is variable depend on tumor size) are injected into the tumor cavity or CSF 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 with an increasing trend in the number of cells and before the start of radiotherapy. With the diagnosis of the physician, the number of injections can be increased.
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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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Iranian academic center for education culture and research
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Proportion provided by this source
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25
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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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Other
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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Parsian Lotus Investment Bank
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Proportion provided by this source
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75
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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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Other
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be 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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Yes - There is a plan to make this available
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Data Dictionary
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Yes - There is a plan to make this available
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Title and more details about the data/document
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The research results with the publication of the article will be provided to researchers.
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When the data will become available and for how long
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To whom data/document is available
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Under which criteria data/document could be used
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From where data/document is obtainable
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What processes are involved for a request to access data/document
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Comments
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