CAR T Cell Therapy for Brain Cancer
Trial Summary
What is the purpose of this trial?
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.
Do I need to stop my current medications to join the trial?
The trial requires you to stop any concurrent anti-cancer therapy at least three half-lives before treatment. You also cannot have received any other forms of immunotherapy within 42 days before the investigational agent or colony-stimulating factors within 14 days prior to lymphodepletion. The protocol does not specify about other medications, so please consult with the trial team for more details.
What data supports the idea that CAR T Cell Therapy for Brain Cancer is an effective treatment?
The available research shows that CAR T Cell Therapy targeting GD2 has shown promise in treating brain cancer. In one study, three out of four patients with a specific type of brain cancer showed improvement after receiving this treatment. Another study found that this therapy could effectively target and kill cancer cells in laboratory models of glioblastoma, a severe brain cancer. Additionally, when compared to other methods, delivering the treatment directly into the brain significantly increased survival time without side effects. These findings suggest that CAR T Cell Therapy could be a promising option for treating certain brain cancers.12345
What safety data is available for CAR T Cell Therapy targeting GD2 in brain cancer?
The safety data for GD2-targeted CAR T cell therapy in brain cancer is mixed. Studies indicate that GD2-specific CAR T cells have been generally well tolerated in clinical trials, with no dose-limiting toxicities reported in some cases. However, there are concerns about neurotoxicity, as seen in preclinical models where GD2 CAR T cells induced fatal neurotoxicity in a costimulatory domain-dependent manner. In another study, peritumoral neuroinflammation during antitumor activity led to lethal hydrocephalus in some animal models. Therefore, while the therapy shows promise, careful monitoring and management are necessary to mitigate potential neurotoxic effects.12678
Is the treatment (C7R)-GD2.CART cells promising for brain cancer?
Yes, the treatment (C7R)-GD2.CART cells is promising for brain cancer. It uses the body's immune system to target and destroy cancer cells, showing potential in treating aggressive brain tumors like glioblastoma and diffuse midline gliomas. Early trials have shown positive results in targeting specific proteins on tumor cells, and it could be transformative for certain childhood brain cancers.19101112
Research Team
Bilal Omer, MD
Principal Investigator
Baylor College of Medicine
Eligibility Criteria
This trial is for children and young adults aged 1 to 21 with specific brain cancers that have a protein called GD2 on their surface. These include newly diagnosed or recurrent tumors like diffuse midline glioma, high-grade glioma, medulloblastoma, and others. Participants need measurable disease on MRI and a functional score indicating they can perform daily activities at least half the time.Inclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Lymphodepletion Chemotherapy
Patients receive cyclophosphamide and fludarabine (or clofarabine) to prepare for T cell infusion
T Cell Infusion and Monitoring
Patients receive GD2-C7R T cells via IV and/or ICV infusion and are monitored for side effects
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- (C7R)-GD2.CART cells
Find a Clinic Near You
Who Is Running the Clinical Trial?
Baylor College of Medicine
Lead Sponsor
Faris Foundation
Collaborator
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborator
Violet Foundation for Pediatric Brain Cancer
Collaborator
The Faris Foundation
Collaborator
ChadTough Defeat DIPG Foundation
Collaborator