C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)
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)
1 other identifier
interventional
56
1 country
1
Brief Summary
In this study, there are two treatment groups called Cohort 1 and Cohort 2. Cohort 1 is for patients with diffuse midline glioma, diffuse intrinsic pontine glioma, medulloblastoma, or another rare high-grade glioma that expresses GD2. Cohort 2 is for patients with a type of cancer called progressive 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 potentially 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. We are now combining an IV infusion with an infusion 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. 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 infusions cycles 2-24. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2020
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 20, 2019
CompletedFirst Posted
Study publicly available on registry
September 23, 2019
CompletedStudy Start
First participant enrolled
February 3, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2041
April 27, 2026
April 1, 2026
7 years
September 20, 2019
April 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (1)
Response rate according to standard criteria
4-6 weeks post T cell infusion
Study Arms (2)
C7R-GD2.CAR T cells (Cohort 1)
EXPERIMENTALThe dose level for autologous cell C7R-GD2.CAR T cells administered via intravenous (IV) infusion was determined in the initial phase of the protocol. The standard IV dose is 20 million cells/m2 with lymphodepletion chemotherapy. In this subsequent phase of the study, the safe dosing levels for autologous cell C7R-GD2.CAR T cell immunotherapy administered intracerebroventricularly (ICV) via ommaya reservoir or programmable VP shunt will be determined.
C7R-GD2.CAR T cells (Cohort 2)
EXPERIMENTALThe dose level for autologous cell C7R-GD2.CAR T cells administered via intravenous (IV) infusion was determined in the initial phase of the protocol. The standard IV dose is 20 million cells/m2 with lymphodepletion chemotherapy. In cycles 2-24, the safe dosing levels for autologous cell C7R-GD2.CAR T cell immunotherapy administered intracerebroventricularly (ICV) via ommaya reservoir or programmable VP shunt will be determined.
Interventions
Dose levels administered are by IV infusion followed by ICV infusion. Cycle 1: 20 million cells/m2 delivered IV with lymphodepletion. Cycle 2 (and subsequent cycles): Dose level 1: 5 million cells ICV with lymphodepletion. Dose level 2: 10 million cells ICV with lymphodepletion. Dose level 3: 15 million cells ICV with lymphodepletion
Eligibility Criteria
You may qualify if:
- Cohort 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.
- 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.
- 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
- Tumors less than 5 cm in maximum dimension at enrollment
- Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study
- 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.
- Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
- Measurable disease on at least 2 dimensions on MRI
- Age 12 months to 25 years
- Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion (≥60 for cohort 2)
You may not qualify if:
- Patients who are pregnant or breast feeding
- 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.
- Cohort 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.
- 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.
- 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 H3K27-altered for DMG or HGG with confirmed GD2-expression.
- Tumors less than 5 cm in maximum dimension at enrollment
- Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study
- 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
- Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
- Measurable disease on at least 2 dimensions on MRI
- Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed. Central line/PICC may be omitted for cycles that do not include lymphodepletion
- Age 12 months to 25 years
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Baylor College of Medicinelead
- Center for Cell and Gene Therapy, Baylor College of Medicinecollaborator
- The Faris Foundationcollaborator
- ChadTough Defeat DIPG Foundationcollaborator
- Violet Foundation for Pediatric Brain Cancercollaborator
- DIPG DMG Research Funding Alliancecollaborator
Study Sites (1)
Texas Children's Hospital
Houston, Texas, 77030, United States
Related Publications (1)
Lin FY, Stuckert A, Tat C, White M, Ruggieri L, Zhang H, Mehta B, Lapteva N, Mei Z, Major A, Thakkar S, Shum T, Parikh K, Wu MF, Lindsay HB, Scherer L, Shekar M, Baxter P, Wang T, Grilley B, Moeller K, Hicks J, Roy A, Anastas J, Malbari F, Aldave G, Chintagumpala M, Blaney S, Parsons DW, Brenner MK, Heslop HE, Rooney CM, Omer B. Phase I Trial of GD2.CART Cells Augmented With Constitutive Interleukin-7 Receptor for Treatment of High-Grade Pediatric CNS Tumors. J Clin Oncol. 2024 Aug 10;42(23):2769-2779. doi: 10.1200/JCO.23.02019. Epub 2024 May 21.
PMID: 38771986DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jasia Mahdi, MD
Baylor College of Medicine
- PRINCIPAL INVESTIGATOR
Bilal Omer, MD
Baylor College of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
September 20, 2019
First Posted
September 23, 2019
Study Start
February 3, 2020
Primary Completion (Estimated)
February 1, 2027
Study Completion (Estimated)
February 1, 2041
Last Updated
April 27, 2026
Record last verified: 2026-04