C7R-GD2 CAR T cells for brain tumors expressing GD2

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)

This study is testing a new treatment using specially modified immune cells to see if they can help people with certain types of brain tumors that have a specific protein called GD2.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 12 Months to 25 Years
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: bevacizumab, immunotherapy, radiation, CAR T, chimeric antigen receptor, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT04099797 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of genetically modified T cells, known as C7R-GD2 CAR T cells, to treat patients with GD2-expressing brain tumors, including diffuse intrinsic pontine glioma and high-grade glioma. Patients will have their T cells collected and modified in the laboratory to enhance their ability to target and kill cancer cells. The modified T cells will then be infused back into the patients through an Ommaya catheter, which is placed prior to treatment. The study aims to evaluate the safety and effectiveness of this innovative immunotherapy approach over a long-term follow-up period.

Who should consider this trial

Good fit: Ideal candidates include patients with GD2-expressing brain tumors, such as diffuse intrinsic pontine glioma or high-grade glioma, who have not responded to standard treatments.

Not a fit: Patients with tumors larger than 5 cm or those without GD2 expression may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with aggressive brain tumors that currently have limited treatment options.

How similar studies have performed: Previous studies using CAR T-cell therapy for other cancers have shown promising results, suggesting potential success for this novel approach in brain tumors.

Eligibility criteria

Procurement Inclusion Criteria:

Cohort 1:

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.

   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.

   Cohort 2:

   Recurrent, refractory, or progressive pontine HGG with confirmed GD2-expression or H3K27-altered DMG
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 25 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 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.

   Cohort 2:

   Recurrent, refractory, or progressive pontine H3K27-altered for DMG or HGG with confirmed GD2-expression.
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. Central line/PICC may be omitted for cycles that do not include lymphodepletion
5. Age 12 months to 25 years
6. Functional score (Karnofsky/Lansky) ≥ 50 (≥60 for cohort 2)
7. 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.
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 (treatment must occur at least three half-lives following prior 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.

Where this trial is running

Houston, Texas

• Texas Children's Hospital — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Jasia Mahdi, MD — Baylor College of Medicine
• Study coordinator: Jasia Mahdi, MD

Conditions Diffuse Intrinsic Pontine Glioma; High Grade Glioma; Embryonal Tumor; Ependymal Tumor; Gene Therapy; CAR T-cells; chimeric antigen receptor; Brain Cancer