Clinical trial NCT05108012: Nk Cell Therapy for Recurrent Glioblastoma Multiform Patients
Official title: The Safety Evaluation of Ex Vivo Activated Haploidentical Natural Killer Cells (NK) in Recurrent Glioblastoma Multiform Patients (Clinical Trial Phase I)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Glioblastoma Multiform
Recurrent Glioblastoma
Keywords: Natural Killer Cells (NK)
Glioblastoma Multiform (GBM)
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
Collaborators: name: Tehran University of Medical Sciences
First posted: 2021-11-04
Enrollment: 5
Sex: ALL
Minimum age (years): 3
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The investigators will enroll 5 patients (3-60 year, both sex, -Lansky performance scale/Karnofsky performance scale: 70-100%) with recurrent Glioblastoma Multiform. A haploidentical donor will enter for each patient.
Primary purpose: TREATMENT

Brief summary: Glioblastoma multiform is one of the most invasive and deadly cancers that progresses rapidly and leads to death. Surgery with radiotherapy /chemotherapy, as a treatment approach is ineffective in some cases and is associated with relapse and death. Immunotherapy is a special strategy that used as an adjunct therapy in various cancers and among the various methods of immunotherapy; it seems that cell therapy with NK cells is of special importance. A previous study conducted at the Royan Research Institute showed that NK cell proliferation and amplification resulted in the removal of glioblastoma tumor masses in the animal model. The animals had no evidence of tumor recurrence after treatment, and all tumor-related complications resolved after treatment. Therefore, in this study, the investigators intend to evaluate the safety of ex vivo activated cells in 5 patients with glioblastoma multiform whose disease has returned after treatment and who have not had any appropriate treatment.

Detailed description: 1- patient selection 2- leukapheresis 3- CD56+ cells isolation 4- NK cells activation 5- assessment of functionality and purity 6- quality control tests 7-NK cell injection in tumor cavity.

Eligibility criteria: Age: 3-60 Year -

* Sex: Both
* Lansky performance scale/Karnofsky performance scale: 70-100%
* Life span expectation: \>6 months
* Hemoglobin: \> 10.0 g/dl
* 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
* No diagnosis of any other invasive cancer within the past 5 years.
* No concurrent serious medical or psychiatric illness that may interfere with giving informed consent or conducting this study

Exclusion Criteria:

* Patients whose MRI and MRS images is in favor of radio necrosis.
* Due to emergency conditions, the patient cannot tolerate the new treatment
* Lack of a suitable donor or insufficient number of NK cells.
* Development of a new neurological defect after the first injection
* Patient death during surgery
* Closing the reservoir for the next injection (if this problem is resolved, the injections will be done again).

Primary outcomes:
measure: Toxicity assay
timeFrame: 4 weeks of last injection
measure: Adverse Events (AEs)
timeFrame: 1 year
measure: Safety evaluation
timeFrame: From injection time point up to 48 hours
measure: Safety evaluation
timeFrame: 2 months after injection
measure: Safety evaluation
timeFrame: From injection time point up to 8 weeks
measure: MRI and MRS from the tumor region
timeFrame: 1 months after last dose of NK cell injection up to 1 year each 3 months
Secondary outcomes:
measure: Patient survival
timeFrame: After surgery up to an average of 1 year
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan institute
Study officials:
affiliation: Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
name: Niloufar Shayan Asl, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
name: Monire Mohammad, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Pediatric cell therapy research center, Tehran University of Medical Sciences
name: Amirali Hamidieh, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
name: Marzieh Ebrahimi, PhD
role: STUDY_DIRECTOR
affiliation: Children's Hospital Medical Center, Tehran University of Medical Science, Tehran, Iran
name: Zohreh Habibi, M.D
role: STUDY_DIRECTOR
affiliation: Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
name: Abolhossein Shahverdi, PhD
role: STUDY_CHAIR
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