Brain Tumor AdultPhase 1DRINCT04165941
Novel Gamma-Delta (γδ)T Cell Therapy for Treatment of Patients With Newly Diagnosed Glioblastoma
A Phase 1 study testing DRI cell therapy in people with Brain Tumor Adult, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Brain Tumor Adult
- What is being tested?
- DRI cell therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2020to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Normal EKG; if abnormal, NCS
- Normal blood presure as adjusted for age
- Creatinine within normal institutional limits or if higher than the normal range, calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (e.g., by Cockcroft-Gault formula); actual body weight must be used for CrCl unless body mass index (BMI) is > 30 kg/m2, in which case, lean body weight must be used
Who cannot join
- Patients who have received any therapy for the treatment of GBM prior to inclusion in Part A and any treatment other than standard of care as described in Part A of this study including: cellular immunotherapy or gene therapy within 6 weeks prior to entering the study, surgical resection or alkylating agent chemotherapy within 4 weeks prior to entering the study, or have received experimental immunotherapy at any time, and those who have not recovered from adverse events due to therapeutic interventions administered more than 4 weeks earlier.
- 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.
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- 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).
- Patients with history of prior organ or bone marrow transplantation are not eligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: A Phase I Study of Drug Resistant Immunotherapy (DRI) With Activated, Gene Modified γδ T Cells in Patients With Newly Diagnosed Glioblastoma Multiforme Receiving Maintenance Temozolomide Chemotherapy
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).
Read the detailed description
The cell therapy that is being used in this study is called gene-modified gamma delta T cells or Drug Resistant Immunotherapy (DRI). Gamma delta T cells are a type of lymphocyte or white blood cell that may help the immune system to recognize and kill cancer cells. Some chemotherapy can kill these gamma delta T cells. For the cell therapy being used in this study, the genes or DNA within these gamma delta T cells are modified so they are resistant to or may not be affected by chemotherapy. The chemotherapy that is being used in this study is called temozolomide (TMZ) and can reduce the number of these gamma delta T cells or lymphocytes. This study will also find out if these modified gamma delta T cells (DRI) are unaffected by TMZ. The DRI is given in combination with a standard dose of TMZ and is administered into the brain where the tumor is located.
After subjects are consented in Parts A and B of the study, approximately about 2 tablespoons of blood will be collected for tests that may provide additional information about subjects T cells and how they may respond to treatment.
Part A Subjects will have a surgical procedure completed that will remove their tumor (called a surgical resection). They will have a Rickham catheter placed which is a device typically used to deliver chemotherapy into the brain. The infusion catheter will be placed first prior to the tumor resection. A sample of tumor tissue will be taken and examined to confirm the diagnosis of GBM. The diagnosis of GBM must be confirmed prior to beginning Part B.
Part B After the surgical resection and on Study Day 1, subjects will return to the study doctor's office/clinic to undergo a procedure called apheresis. This procedure will separate out cells called peripheral blood mononuclear cells (PBMC). Apheresis is the removal of blood plasma from the body by collecting your blood and separating the plasma from the PBMCs. These cells include the gamma delta T cells that will be used to synthesize the DRI γδ T cells. Once the cells for the DRI γδ T cells are synthesized, they are reintroduced into subject's brain through the Rickham catheter.
Following apheresis and confirmation that the required number of gamma delta T cells were collected, subjects will begin the recommended or standard of care treatment for newly diagnosed GBM. This will include 6 weeks of chemotherapy with TMZ and radiation. Subjects will then have about 4 weeks of no treatment prior to beginning the Part B maintenance phase of treatment, which includes 6 cycles of TMZ. Depending on which dose level they receive, they will be administered either 1 injection of the DRI γδ T cells or 3 and these will be injected through the Rickham catheter.
The first 3 subjects will receive a single dose of the DRI γδ T cells at the lowest dose level. Subjects receiving a single dose of the DRI γδ T cells will be observed for a of minimum 30 days from the time the first subject is enrolled, followed by a minimum of 7 days between each additional subject enrolled to allow for evaluation of potential side effects. If the DRI γδ T cell injection does not cause serious side effects, the second set of 3 subjects will be enrolled. The second set of 3 patients will receive 3 doses of the DRI γδ T cells. The approximate duration of the study may be up to 15 years, or until disease progression or subjects withdraw from the study.
- Conditions
- Brain Tumor Adult
- Being tested
- DRI cell therapy
- Keywords
- Newly diagnosed brain tumor, Phase 1, Drug Resistant Immunotherapy, Temozolomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DRI cell therapyBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: DRI cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
Secondary outcomes (3)
Time to progression
Time to disease progression
Measured: Through study completion, on average one year
Overall survival
Time that participants survive
Measured: Through study completion, on average one year
Assessment of biological activity
Serum measurements of cell therapy activity
Measured: Through study completion, on average one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start11 Feb 2020
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Brain Tumor AdultStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Louis Burt Nabors, MD, University of Alabama at Birmingham
- Investigators
- Louis B Nabors, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04165941
- Sponsor's protocol ID
- UAB 1773
- Acronym
- DRI
- Status last verified
- Dec 2025
- First submitted
- 12 Nov 2019
- Last updated
- 26 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38384458Zhao 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.
PubMed 37592858
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Drug Resistant Immunotherapy (DRI) With Activated, Gene Modified γδ T Cells in Patients With Newly Diagnosed Glioblastoma Multiforme Receiving Maintenance Temozolomide Chemotherapy
- ClinicalTrials.gov ID
- NCT04165941
- Acronym / sponsor ID
- DRI / UAB 1773
- Conditions
- Brain Tumor Adult
- Keywords
- Newly diagnosed brain tumor, Phase 1, Drug Resistant Immunotherapy, Temozolomide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 11 Feb 2020 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 18 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The cell therapy that is being used in this study is called gene-modified gamma delta T cells or Drug Resistant Immunotherapy (DRI). Gamma delta T cells are a type of lymphocyte or white blood cell that may help the immune system to recognize and kill cancer cells. Some chemotherapy can kill these gamma delta T cells. For the cell therapy being used in this study, the genes or DNA within these gamma delta T cells are modified so they are resistant to or may not be affected by chemotherapy. The chemotherapy that is being used in this study is called temozolomide (TMZ) and can reduce the number of these gamma delta T cells or lymphocytes. This study will also find out if these modified gamma delta T cells (DRI) are unaffected by TMZ. The DRI is given in combination with a standard dose of TMZ and is administered into the brain where the tumor is located.
After subjects are consented in Parts A and B of the study, approximately about 2 tablespoons of blood will be collected for tests that may provide additional information about subjects T cells and how they may respond to treatment.
Part A Subjects will have a surgical procedure completed that will remove their tumor (called a surgical resection). They will have a Rickham catheter placed which is a device typically used to deliver chemotherapy into the brain. The infusion catheter will be placed first prior to the tumor resection. A sample of tumor tissue will be taken and examined to confirm the diagnosis of GBM. The diagnosis of GBM must be confirmed prior to beginning Part B.
Part B After the surgical resection and on Study Day 1, subjects will return to the study doctor's office/clinic to undergo a procedure called apheresis. This procedure will separate out cells called peripheral blood mononuclear cells (PBMC). Apheresis is the removal of blood plasma from the body by collecting your blood and separating the plasma from the PBMCs. These cells include the gamma delta T cells that will be used to synthesize the DRI γδ T cells. Once the cells for the DRI γδ T cells are synthesized, they are reintroduced into subject's brain through the Rickham catheter.
Following apheresis and confirmation that the required number of gamma delta T cells were collected, subjects will begin the recommended or standard of care treatment for newly diagnosed GBM. This will include 6 weeks of chemotherapy with TMZ and radiation. Subjects will then have about 4 weeks of no treatment prior to beginning the Part B maintenance phase of treatment, which includes 6 cycles of TMZ. Depending on which dose level they receive, they will be administered either 1 injection of the DRI γδ T cells or 3 and these will be injected through the Rickham catheter.
The first 3 subjects will receive a single dose of the DRI γδ T cells at the lowest dose level. Subjects receiving a single dose of the DRI γδ T cells will be observed for a of minimum 30 days from the time the first subject is enrolled, followed by a minimum of 7 days between each additional subject enrolled to allow for evaluation of potential side effects. If the DRI γδ T cell injection does not cause serious side effects, the second set of 3 subjects will be enrolled. The second set of 3 patients will receive 3 doses of the DRI γδ T cells. The approximate duration of the study may be up to 15 years, or until disease progression or subjects withdraw from the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DRI cell therapy | Experimental | Biological: DRI cell therapyThe only arm will receive the DRI modified gamma delta T cells following standard therapy with radiation and temozolomide chemotherapy concurrent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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%
Key exclusion criteria (17 listed)
- Patients who have received any therapy for the treatment of GBM prior to inclusion in Part A and any treatment other than standard of care as described in Part A of this study including: cellular immunotherapy or gene therapy within 6 weeks prior to entering the study, surgical resection or alkylating agent chemotherapy within 4 weeks prior to entering the study, or have received experimental immunotherapy at any time, and those who have not recovered from adverse events due to therapeutic interventions administered more than 4 weeks earlier.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DRI cell therapyDrug 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. | Biological | DRI cell therapy |
Primary outcome
Primary: Highest safe dose frequency or maximally planned dose, if no dose-limiting toxicity observed.
Time frame: 12 weeks
Safety and toxicity of intracranially infused DRI gamma delta T cells
3 secondary outcomes
Time to progression
Time frame: Through study completion, on average one year
Overall survival
Time frame: Through study completion, on average one year
Assessment of biological activity
Time frame: Through study completion, on average one year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2025.
- Derived from this study: PubMed 38384458Nabors 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.
- Derived from this study: PubMed 37592858Zhao 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louis B Nabors, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DRI cell therapy in people with Brain Tumor Adult, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary: Highest safe dose frequency or maximally planned dose, if no dose-limiting toxicity observed. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04165941, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2025.