Nk Cell Therapy for Recurrent Glioblastoma Multiform Patients

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

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Glioblastoma; Glioblastoma Multiform
• Intervention / Treatment: Biological: NK cell therapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Marzieh Ebrahimi, PhD; Phone Number: +98 21 235 62516; Email: marzieh.ebrahimi@gmail.com;mebrahimi@royan-rc.ac.ir
• Study Contact Backup: Name: Zohreh Habibi, M.D; Phone Number: +98 912 336 5598; Email: z-habibi@gmail.com

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, Postal code:1665659911
    • Recruiting
    • Royan Institute
    • Contact: Niloufar Shayan Asl, MSc; Phone Number: +98 21 23 56 25 21; Email: niloufar.shayanasl@gmail.com
    • Contact: Monire Mohammad, MSc; Phone Number: +98 21 23 56 25 21; Email: monirmohamad@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Royan Institute
• Collaborators: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Niloufar Shayan Asl, MSc, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Principal Investigator: Monire Mohammad, MSc, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Principal Investigator: Amirali Hamidieh, MD,PhD, Pediatric cell therapy research center, Tehran University of Medical Sciences; Study Director: Marzieh Ebrahimi, PhD, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Study Director: Zohreh Habibi, M.D, Children's Hospital Medical Center, Tehran University of Medical Science, Tehran, Iran; Study Chair: Abolhossein Shahverdi, PhD, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: October 23, 2021
• First Posted (Actual): November 4, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 13, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Natural Killer Cells (NK); Glioblastoma Multiform (GBM)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: GMB1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No