Novel Gamma-Delta (γδ)T Cell Therapy for Treatment of Patients With Newly Diagnosed Glioblastoma (DRI)
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|ClinicalTrials.gov Identifier: NCT04165941|
Recruitment Status : Not yet recruiting
First Posted : November 18, 2019
Last Update Posted : November 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Brain Tumor Adult||Biological: DRI cell therapy||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||January 2020|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||January 2023|
Experimental: DRI cell therapy
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
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.
- 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
- Time to progression [ Time Frame: Through study completion, on average one year ]Time to disease progression
- Overall survival [ Time Frame: Through study completion, on average one year ]Time that participants survive
- Assessment of biological activity [ Time Frame: Through study completion, on average one year ]Serum measurements of cell therapy activity
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04165941
|Contact: Louis B Nabors, MDemail@example.com|
|Contact: Thiru Pillay, BSNfirstname.lastname@example.org|
|Principal Investigator:||Louis B Nabors, MD||University of Alabama at Birmingham|