Nk Cell Therapy for Recurrent Glioblastoma Multiform Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Safety Evaluation of Ex Vivo Activated Haploidentical Natural Killer Cells (NK) in Recurrent Glioblastoma Multiform Patients (Clinical Trial Phase I)

Conditions
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Glioblastoma Multiform, Recurrent Glioblastoma

Intervention / Treatment
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* Biological: NK cell therapy


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group<br>The investigators will inject the activated NK cells, 1-3 times with weekly interval into tumor cavity. | Biological: NK cell therapy<br>* Activated NK cell injection in tumor cavity of patient with GBM (Glioblastoma Multiform)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity assay | Toxicity as assessed by NCI CTCAE version 3.0 | 4 weeks of last injection | 
| Adverse Events (AEs) | Defined as the number and severity of adverse events | 1 year | 
| Safety evaluation | Safety evaluated by assessing the medical symptoms measurement: Fever, Hysteria and Convulsion | From injection time point up to 48 hours | 
| Safety evaluation | Safety evaluated by assessing the medical symptoms measurement: Meningitis, Neurological disorders | 2 months after injection | 
| Safety evaluation | Safety evaluated by assessing the medical symptoms measurement: Loss of consciousness | From injection time point up to 8 weeks | 
| MRI and MRS from the tumor region | Defined tumoral residua and tumor cell recurrence | 1 months after last dose of NK cell injection up to 1 year each 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient survival | Evaluation of patient's life extension followed by NK cell therapy | After surgery up to an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Natural Killer Cells (NK), Glioblastoma Multiform (GBM)