C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)
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|ClinicalTrials.gov Identifier: NCT04099797|
Recruitment Status : Recruiting
First Posted : September 23, 2019
Last Update Posted : February 23, 2022
This study is for patients with high grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) or medulloblastoma or another rare brain cancer that expresses GD2. Because there is no standard treatment at this time, patients are being 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.
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. 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.
We have found from previous research that we 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. When we and other researchers tested DIPG/HGG cancer cells we found that many of these cancers also have GD2 on their surface.
In a study for neuroblastoma in children, we made a gene called a chimeric antigen receptor (CAR) from an antibody that recognizes GD2. We put this gene into the patients' own T cells and gave them back to 11 patients. We saw that the cells did grow for a while but started to disappear from the blood after 2 weeks. We think that if T cells are able to last longer they may have a better chance of killing tumor cells.
In this study, we will add a new gene to the GD2 T cells that can cause the cells to live longer. We know that T cells need substances called cytokines to survive. We have added the gene C7R 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 some 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 we think that it will allow the T cells to expand and stay longer in the body and potentially kill cancer cells more effectively.
The GD2.C7R T cells are an investigational product not approved by the Food and Drug Administration.
The purpose of this study is to find the largest safe dose of GD2-C7R T cells, and also to evaluate how long they can be detected in the blood and what affect they have on brain cancer.
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Intrinsic Pontine Glioma High Grade Glioma Embryonal Tumor Ependymal Tumor||Genetic: (C7R)-GD2.CART cells Drug: Cyclophosphamide Drug: Fludarabine||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||February 3, 2020|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||February 2038|
Experimental: C7R-GD2.CAR T cells
This is a single arm study. Patients will be treated at 4 dose levels. At dose level 0, patients will only receive GD2.CART cells without C7R and they will receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine. Three patients will be evaluated and if safety is confirmed patients will be treated with lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by C7R.GD2.CART cell infusion at 3 dose levels.
Genetic: (C7R)-GD2.CART cells
Patients at all dose levels will receive lymphodepletion chemotherapy. They will receive 2 daily doses of cyclophosphamide (500mg/m2/day) finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle).
Other Name: Cytoxan
Patients at all dose levels will receive lymphodepletion chemotherapy. They will receive 3 daily doses of fludarabine (30mg/m2/day) finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle).
Other Name: Fludara
- Dose limiting toxicity (DLT) rate [ Time Frame: 4 weeks post T cell infusion ]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.
- Response rate according to standard criteria [ Time Frame: 6 and 12 weeks post T cell infusion ]Anti-tumor response to (C7R)-GD2.CART cell therapy will be evaluated by Magnetic Resonance Imaging (MRI)
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): NCT04099797
|Contact: Bilal Omer, MDfirstname.lastname@example.org|
|Contact: David Allenemail@example.com|
|Principal Investigator:||Bilal Omer, MD||Baylor College of Medicine|