Novel Gamma-Delta (γδ)T Cell Therapy for Treatment of Patients With Newly Diagnosed Glioblastoma

NCT04165941 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: UAB 1773
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to find out if the safety and tolerability of an experimental cell therapy is safe to administer to patients with a newly diagnosed glioblastoma multiforme (GBM) in combination with temozolomide (TMZ).

Conditions

Brain Tumor Adult

Keywords

Newly diagnosed brain tumor; Phase 1; Drug Resistant Immunotherapy; Temozolomide

Outcome Measures

Primary Outcomes (1)

• Primary: Highest safe dose frequency or maximally planned dose, if no dose-limiting toxicity observed.

  Safety and toxicity of intracranially infused DRI gamma delta T cells

  12 weeks

Secondary Outcomes (3)

• Time to progression

  Through study completion, on average one year

• Overall survival

  Through study completion, on average one year

• Assessment of biological activity

  Through study completion, on average one year

Study Arms (1)

DRI cell therapy

EXPERIMENTAL

The only arm will receive the DRI modified gamma delta T cells following standard therapy with radiation and temozolomide chemotherapy concurrent.

Biological: DRI cell therapy

Interventions

DRI cell therapy BIOLOGICAL

Drug Resistant Immunotherapy with gamma delta modified T cells to be resistance to temozolomide will be infused into the surgical cavity following the completion of standard concurrent radiation and chemotherapy with temozolomide.

DRI cell therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have magnetic resonance imaging (MRI) features consistent with and suspicious for malignant glioma. This will be Part A - Tissue (biopsy) and Rickham catheter placement.
• Must have histologically or cytologically confirmed glioblastoma multiforme prior to administration of the DRI γδ T cell injection. This will be Part B - Screening and Study Treatment.
• Prior therapy: Must have completed a standard temozolomide and radiotherapy treatment as described in Part A and be eligible to receive maintenance therapy with temozolomide (consistent with NCCN guidelines for newly diagnosed GBM and maintenance therapy).
• Age ≥18 yearsΦ: Because no dosing or adverse event data are currently available on the use of γδ T cells in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric Phase I single-agent trials.
• Karnofsky Performance Status ≥70%
• Life expectancy of greater than 12 weeks
• Patients must have organ and marrow function as defined below:
• leukocytes \>3,000/µl
• absolute neutrophil count \>1,500/µl
• Hgb greater than or equal to 9.0 g/dL
• platelets \>100,000/µl
• total bilirubin within normal institutional limits
• AST (SGOT)/ALT (SGPT) \<2.5 X institutional upper limit of normal
• Normal electrolyte levels including sodium, calcium, potassium, chloride and magnesium
• INR/PT/aPTT ≤1.5xULN

You may not qualify if:

• Patients may not be receiving any other investigational agents.
• Contraindication to the placement of an intracranial access device (Rickham catheter) at the time of surgery.
• Prior history of encephalitis, multiple sclerosis, or other CNS infection
• Required steroid increase within 2 weeks of scheduled DRI γδ T cells administration.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any othermedical condition that precludes surgery. Also, psychiatric illness/social situations that would limit compliance with study requirements.
• Allergies/hypersensitivity: Aminobisphosphonates such as Zoledronate®, Pamidronate® or similar
• Pregnant women are excluded from this study because the lentiviral- modified γδ T cells designed to express MGMT cells have an unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these cells, breastfeeding should be discontinued if the mother is treated with the lentiviral-modified γδ T cells designed to express MGMT. The following birth control methods are acceptable for this study in women of child- bearing potential:
• A Combination of TWO of the following:
• Barrier method of contraception:
• condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide
• IUD
• Hormone-based Contraceptive
• Note: Drug-drug interactions with some ARVs will make hormonal contraception a less reliable method.
• Because patients with immune deficiency will be unable to mount the anticipated immune response underlying this therapeutic rationale, HIV-seropositive patients are excluded from this study.
• Some of the contraceptive methods listed above may not prevent the spread of HIV to other people. Patients should discuss their contraceptive choices with their health care provider to choose the best way to both prevent pregnancy as required by this study and to prevent the spread of HIV to any partner(s).

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (2)

• Nabors LB, Lamb LS, Goswami T, Rochlin K, Youngblood SL. Adoptive cell therapy for high grade gliomas using simultaneous temozolomide and intracranial mgmt-modified gammadelta t cells following standard post-resection chemotherapy and radiotherapy: current strategy and future directions. Front Immunol. 2024 Feb 7;15:1299044. doi: 10.3389/fimmu.2024.1299044. eCollection 2024.

  PMID: 38384458 DERIVED

• Zhao Y, Dong P, He W, Zhang J, Chen H. gammadelta T cells: Major advances in basic and clinical research in tumor immunotherapy. Chin Med J (Engl). 2024 Jan 5;137(1):21-33. doi: 10.1097/CM9.0000000000002781. Epub 2023 Aug 18.

  PMID: 37592858 DERIVED

Study Officials

• Louis B Nabors, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Neurology Chair Office

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 18, 2019
• Study Start: February 11, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)