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RECRUITING

NCT04099797

PHASE1

C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)

Sponsor: Baylor College of Medicine

View on ClinicalTrials.gov

Summary

In this study, there are two treatment groups called Cohort 1 and Cohort 2. Cohort 1 is for patients with diffuse midline glioma, high grade glioma, diffuse intrinsic pontine glioma, medulloblastoma, or another rare brain cancer that expresses GD2. Cohort 2 is for patients with a type of cancer called progressive pontine diffuse midline glioma (DMG), high grade glioma or diffuse intrinsic pontine glioma 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, we will combine IV infusions 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. Patients will now be assigned to Cohort 1 and 2 based on their tumor type with different dose levels for each cohort. The GD2.C7R T cells are an investigational product not approved by the FDA. The purpose of this study is to combine infusions into the vein in the first treatment cycle with infusions directly into the cerebrospinal fluid (CSF) in the brain (intracerebroventricularly) through the ommaya reservoir or programmable VP shunt for the second infusion cycle and possibly additional infusions after that. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way, and additionally to evaluate how long they can be detected in the blood and CSF and what affect they have on brain cancer.

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)

Key Details

Gender

All

Age Range

12 Months - 22 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2020-02-03

Completion Date

2041-02

Last Updated

2025-09-04

Healthy Volunteers

Conditions

Diffuse Intrinsic Pontine Glioma High Grade Glioma Embryonal Tumor Ependymal Tumor

Interventions

GENETIC

C7R-GD2.CART cells (IV and ICV infusion)

Dose levels administered are by IV infusion followed by ICV infusion. Cycle 1: 10 million cells/m2 delivered IV with lymphodepletion. Cycle 2 (and subsequent cycles): Dose level 1: 2 million cells ICV with lymphodepletion. Dose level 2: 5 million cells ICV with lymphodepletion.

GENETIC

C7R-GD2.CAR T cells (IV infusion)

Dose levels administered are by IV infusion. For all cycles, the dose level is 10 million cells/m2 IV with lymphodepletion.

Procurement Inclusion Criteria: Cohort 1: 1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence. OR Histologically confirmed, GD2-expressing recurrent, refractory, or progressive DMG/HGG (except pontine) or confirmation of positive H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. OR Recurrent, refractory, or progressive high-grade CNS tumor with confirmed GD2-expression. Examples include: medulloblastoma "CNS embryonal tumors, AT/RT, ependymal tumors, diffuse gliomas or glioneuronal tumors. Cohort 2: Recurrent, refractory, or progressive pontine HGG with confirmed GD2-expression or H3K27-altered DMG 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 22 years 5. Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion (≥60 for cohort 2) 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 Cohort 1: 1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence. OR Histologically confirmed, GD2-expressing recurrent, refractory, or progressive DMG/HGG (except pontine) or confirmation of positive H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. OR Recurrent, refractory, or progressive high -grade CNS tumor with confirmed GD2-expression. Examples include: medulloblastoma, CNS embryonal tumors, AT/RT, ependymal tumors, diffuse gliomas, or glioneuronal tumors. Cohort 2: Recurrent, refractory, or progressive pontine HGG with confirmed GD2-expression or H3K27-altered for DMG. 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 22 years 6. Functional score (Karnofsky/Lansky) ≥ 50 (≥60 for cohort 2) 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.

Locations (1)

Texas Children's Hospital

Houston, Texas, United States