High Grade Glioma Clinical Trial
Official title:
Phase I Study of Autologous T Lymphocytes Expressing GD2-specific Chimeric Antigen and Constitutively Active IL-7 Receptors for the Treatment of Patients With GD2-expressing Brain Tumors (GAIL-B)
This study is for patients with diffuse midline glioma, high grade glioma, diffuse intrinsic pontine glioma, medulloblastoma, or another rare brain cancer that expresses GD2. Because there is no standard treatment at this time, patients are asked to volunteer in a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that help the body fight infection. This research study combines two different ways of fighting cancer: antibodies and T cells. Both antibodies and T cells have been used to treat cancer patients. They have shown promise but have not been strong enough to cure most patients. Researchers have found from previous research that they can put a new antibody gene into T cells that will make them recognize cancer cells and kill them. GD2 is a protein found on several different cancers. Researchers testing brain cancer cells found that many of these cancers also have GD2 on their surface. In a study for neuroblastoma in children, a gene called a chimeric antigen receptor (CAR) was made from an antibody that recognizes GD2. This gene was put into the patients' own T cells and given back to 11 patients. The cells did grow for a while but started to disappear from the blood after 2 weeks. The researchers think that if T cells are able to last longer they may have a better chance of killing tumor cells. In this study, a new gene will be added to the GD2 T cells that can cause the cells to live longer. T cells need substances called cytokines to survive. The gene C7R has been added that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. In other studies using T cells researchers found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and it will allow the T cells to expand and stay longer in the body and potentially kill cancer cells more effectively. After treating 11 patients, the largest safe dose of GD2-CAR T cells given in the vein (IV) was determined. Going forward, IV infusions will be combined with infusions directly into the brain through the Ommaya reservoir or programmable VP shunt. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way. The GD2.C7R T cells are an investigational product not approved by the FDA.
Status | Recruiting |
Enrollment | 34 |
Est. completion date | February 2039 |
Est. primary completion date | February 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 12 Months to 21 Years |
Eligibility | Procurement Inclusion Criteria: 1. Patients with histologically confirmed, GD2-expressing newly diagnosed DMG (DIPG or HGG) or confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence OR Recurrent or refractory intracranial embryonal tumor, HGG/DMG except DIPG (HGG) or ependymal tumor with confirmed GD2-expression (or H3K27M+ for HGG) Examples of embryonal tumors include: medulloblastoma, "PNET", AT/RT 2. Tumors less than 5 cm in maximum dimension at enrollment 1. Tumors with =25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study 2. Tumors with >25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently = 25% increased compared with pre-irradiation MRI. 3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked 3. Measurable disease on at least 2 dimensions on MRI 4. Age 12 months to 21 years 5. Functional score (Karnofsky/Lansky) = 50 expected at infusion Procurement Exclusion Criteria: 1. Patients who are pregnant or breast feeding 2. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator. Treatment Inclusion Criteria 1. Patients with histologically confirmed, GD2-expressing newly diagnosed DMG (DIPG or HGG) or confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence OR Recurrent or refractory intracranial embryonal tumor, HGG/DMG except DIPG (HGG) or ependymal tumor with confirmed GD2-expression (or H3K27M+ for HGG) Examples of embryonal tumors include: medulloblastoma, "PNET", AT/RT 2. Tumors less than 5 cm in maximum dimension at enrollment 1. Tumors with =25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study 2. Tumors with >25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently = 25% increased compared pre-irradiation MRI 3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked 3. Measurable disease on at least 2 dimensions on MRI 4. Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed 5. Age 12 months to 21 years 6. Functional score (Karnofsky/Lansky) = 50 7. Patients must have completed radiation therapy at least 4 weeks prior to administration of investigational agent. Radiation therapy and (If applicable) bevacizumab treatment for radiation necrosis must be completed at least 4 weeks prior to administration of investigational agent. 8. Stable neurologic exam for 7 days prior to enrollment 9. Stable or decreasing dose of steroids (max. allowable dose of dexamethasone is 0.1 mg/kg/day over the past 7 days prior to infusion of investigational therapy) 10. Organ function: 1. ANC > 1000 cells/ul 2. Platelet count > 100,000 cells/ul 3. Total bilirubin < 1.5x ULN 4. ALT and AST < 5x ULN 5. Serum creatinine or kidney within 2x ULN for age Treatment Exclusion Criteria 1. Patients who received any other forms of immunotherapy = 42 days before administration of investigational agent 2. Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion 3. Patients receiving any concurrent anti-cancer therapy (it is preferable for patients to stop any concurrent anti-cancer therapy at least three half-lives prior to treatment) 4. Patients who are pregnant or breast feeding 5. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator. |
Country | Name | City | State |
---|---|---|---|
United States | Texas Children's Hospital | Houston | Texas |
Lead Sponsor | Collaborator |
---|---|
Baylor College of Medicine | Center for Cell and Gene Therapy, Baylor College of Medicine, ChadTough Defeat DIPG Foundation, The Faris Foundation, Violet Foundation for Pediatric Brain Cancer |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Dose limiting toxicity (DLT) rate | DLT rate is defined as the proportion of subjects with DLT evaluated as per the NCI CTCAE v5.0 with the exception of CRS and neurological toxicities that are related to T cell infusions. | 4 weeks post T cell infusion | |
Secondary | Response rate according to standard criteria | Anti-tumor response to (C7R)-GD2.CART cell therapy will be evaluated by Magnetic Resonance Imaging (MRI) | 6 and 12 weeks post T cell infusion |
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