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

Launched by BAYLOR COLLEGE OF MEDICINE · Sep 20, 2019

Keywords

ClinConnect Summary

This clinical trial, called GAIL-B, is exploring a new treatment for patients with specific types of brain tumors that express a protein called GD2, such as diffuse intrinsic pontine glioma and other high-grade gliomas. Since traditional treatments haven’t been very effective for these conditions, the study aims to use a special type of immune cell, called CAR T cells, which have been modified to recognize and attack cancer cells. The researchers hope to improve the effectiveness of these T cells by adding a gene that helps them survive longer in the body, allowing them to fight the tumors more effectively.

To participate in this trial, patients must be between 12 months and 21 years old, have a confirmed GD2-expressing tumor that is less than 5 cm in size, and have completed prior radiation therapy at least four weeks before starting this study. Participants can expect to receive infusions of these modified T cells both through an IV and directly into the brain, if applicable. It's important to note that this treatment is still being tested and has not yet been approved by the FDA. This trial offers hope for patients with limited treatment options, as it combines advanced cancer-fighting techniques with the goal of improving outcomes for these challenging tumors.

Gender

ALL

Eligibility criteria

• Procurement Inclusion Criteria:
• Cohort 1:
• • 1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of positive H3K27M alteration status 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 H3K27M alteration status if sufficient tissue for GD2 staining by IHC is not available.
• • OR
• • Recurrent, refractory, or progressive CNS embryonal tumor, or ependymal tumor with confirmed GD2-expression Examples of embryonal tumors include: medulloblastoma "PNET", AT/RT.
• Cohort 2:
• • Recurrent, refractory, or progressive pontine DMG/HGG with confirmed GD2-expression (of H3K27M-altered for HGG)
• • 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 pre-irradiation MRI.
• • 3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
• • 3. Measurable disease on at least 2 dimensions on MRI
• • 4. Age 12 months to 22 years
• • 5. Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion (≥60 for cohort 2)
• 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
• Cohort 1:
• • 1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of positive H3K27M alteration status 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 H3K27M alteration status if sufficient tissue for GD2 staining by IHC is not available.
• • OR
• • Recurrent, refractory, or progressive CNS embryonal tumor, or ependymal tumor with confirmed GD2-expression. Examples of embryonal tumors include: medulloblastoma "PNET", AT/RT.
• Cohort 2:
• • Recurrent, refractory, or progressive pontine DMG/HGG with confirmed GD2-expression (of H3K27M-altered for HGG)
• • 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 pre-irradiation MRI
• • 3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
• • 3. Measurable disease on at least 2 dimensions on MRI
• • 4. Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed
• • 5. Age 12 months to 22 years
• • 6. Functional score (Karnofsky/Lansky) ≥ 50 (≥60 for cohort 2)
• • 7. Patients must have completed radiation therapy at least 4 weeks prior to administration of investigational agent. Radiation therapy and (If applicable) bevacizumab treatment for radiation necrosis 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 (it is preferable for patients to stop any concurrent anti-cancer therapy at least three half-lives prior to treatment)
• • 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.