What this study is
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.
What's being tested
- C7R-GD2.CART cells (IV and ICV infusion)
Intervention · GENETIC
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
- C7R-GD2.CART cells (IV and ICV infusion)
Intervention · GENETIC
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
Study details
- 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)
- Sponsor
- Baylor College of Medicine
- Conditions
- Diffuse Intrinsic Pontine Glioma · High Grade Glioma · Embryonal Tumor · Ependymal Tumor
- Enrolling
- 56 people
- Starts
- 2020-02-03
- Est. completion
- 2041-02
- Design
- Open-label, non-randomized, parallel groups, Phase 1
- Record
- View on ClinicalTrials.gov ↗
Who can join
Age 12 Months – 25 YearsSex ALLHealthy volunteers Not acceptedCohort 1
You may qualify if
- 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.
- 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.
You can't join 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.
- Patients who received any other forms of immunotherapy ≤ 42 days before administration of investigational agent
- Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion
- Patients receiving any concurrent anti-cancer therapy (treatment must occur at least three half-lives following prior anti-cancer therapy)
- 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 2
You may qualify if
- 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)
- 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
- Functional score (Karnofsky/Lansky) ≥ 50 (≥60 for cohort 2)
- Patients must have completed standard of care radiation therapy at least 4 weeks prior to administration of investigational agent. If bevacizumab was administered for management of radiation necrosis, therapy must be completed at least 4 weeks prior to administration of investigational agent.
- Stable neurologic exam for 7 days prior to enrollment
- 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)
- Organ function:; ANC > 1000 cells/ul; Platelet count > 100,000 cells/ul; Total bilirubin < 1.5x ULN; ALT and AST < 5x ULN; Serum creatinine or kidney within 2x ULN for age
You can't join 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.
- Patients who received any other forms of immunotherapy ≤ 42 days before administration of investigational agent
- Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion
- Patients receiving any concurrent anti-cancer therapy (treatment must occur at least three half-lives following prior anti-cancer therapy)
- 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.
Sign in and we'll check these against your records.Full criteria on ClinicalTrials.gov ↗
Loading treatment details…
Study locations (1)
1 openTexas Children's Hospital
Houston, Texas, United States
- Bilal Omer, MD · Contact832-824-6855bomer@bcm.edu
- David Allen · Contact832-824-4391dlallen@bcm.edu
Recruiting
Study team
Sponsor
Baylor College of Medicine
Study ID H-45668 GAIL-B
Principal investigator
Jasia Mahdi, MD
Baylor College of Medicine
Principal investigator
Bilal Omer, MD
Baylor College of Medicine
Frequently asked questions
The sponsor hasn't published answers to common questions for this trial.