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

• Status: Recruiting
• Trial end date: 2038-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine; Texas Children's Hospital
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

Procurement Inclusion Criteria:

1. Patients with histologically confirmed, GD2-expressing newly diagnosed DIPG or HGG or confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence OR Recurrent or refractory intracranial embryonal tumor, HGG or ependymal tumor with confirmed GD2-expression (or H3K27M+ for HGG) Examples of embryonal tumors include: medulloblastoma, "PNET", AT/RT

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 time of diagnosis

3. Measurable disease on at least 2 dimensions on MRI

4. Age 12 months to 18 years

5. Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion

6. 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

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

1. Patients with histologically confirmed, GD2-expressing newly diagnosed DIPG or HGG or confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence OR Recurrent or refractory intracranial embryonal tumor, HGG or ependymal tumor with confirmed GD2-expression (or H3K27M+ for HGG) Examples of embryonal tumors include: medulloblastoma, "PNET", AT/RT

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 time of diagnosis

3. Measurable disease on at least 2 dimensions on MRI

4. Central line (PICC or other) and Ommaya reservoir in place or planned to be placed

5. Age 12 months to 18 years

6. Functional score (Karnofsky/Lansky) ≥ 50

7. Completed standard of care radiation therapy. If bevacizumab was administered for management of radiation necrosis, therapy 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

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.