Using modified immune cells to treat children with neuroblastoma

GD2 Specific Chimeric Antigen Receptor (CAR) and Interleukin-15 Expressing Autologous Natural Killer T-cells to Treat Children With Neuroblastoma

This study is testing a new treatment for children with tough-to-treat neuroblastoma by using specially modified immune cells to see if they can help fight the cancer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 1 Year to 21 Years
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine, chimeric antigen receptor
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT03294954 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to treat children with relapsed or refractory high-risk neuroblastoma by using genetically modified Natural Killer T (NKT) cells that express a chimeric antigen receptor (CAR) targeting the GD2 molecule found on neuroblastoma cells. The study involves a dose escalation approach, where patients will receive varying doses of these modified cells after undergoing a preparatory chemotherapy regimen. The safety and efficacy of the treatment will be monitored closely, with adjustments made based on patient responses and side effects. The trial is conducted at Texas Children's Hospital under the guidance of Baylor College of Medicine.

Who should consider this trial

Good fit: Ideal candidates for this study are children aged 1 to 21 years with relapsed or refractory high-risk neuroblastoma.

Not a fit: Patients with low-risk neuroblastoma or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new, effective option for children with difficult-to-treat neuroblastoma.

How similar studies have performed: Previous studies using CAR T-cell therapies have shown promising results in treating various cancers, indicating potential success for this novel approach.

Eligibility criteria

Procurement Inclusion Criteria:

1. Relapsed or refractory high risk neuroblastoma
2. Life expectancy of at least 12 weeks
3. Age greater than 1 year and less than 21 years old
4. Karnofsky/Lansky score of 60% or greater
5. Absence of HAMA prior to enrollment (only in patients that have been previously treated with murine antibodies)
6. Ability to tolerate leukocyte apheresis
7. Informed consent and assent (as applicable) obtained from parent/guardian and child.
8. Patients must have an ANC greater than or equal to 500/µl, platelet count greater than or equal to 20,000/µl. Patients may be transfused to obtain a platelet count greater than or equal to 20,000/µl.
9. Pulse Ox greater than or equal to 90% on room air
10. Serum AST less than 3 times the upper limit of normal
11. Total Bilirubin less than 1.5 times the upper limit of normal
12. Creatinine \< 1.5 times the upper limit of normal
13. Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
14. Weight greater than 12kg
15. Negative QuantiFERON-TB or T-SPOT testing within 3 months prior to procurement

Procurement Exclusion Criteria:

1. Rapidly progressive disease
2. History or hypersensitivity to murine protein-containing products
3. Tumor causing airway obstruction
4. Currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine
5. Severe previous toxicity from cyclophosphamide or fludarabine based on the enrolling physician's assessment
6. HIV infection
7. History of hypersensitivity, anaphylaxis, and/or adverse event with Etanercept

Treatment Inclusion Criteria:

1. Relapsed or refractory high risk neuroblastoma
2. Life expectancy of at least 12 weeks
3. Age greater than 1 year and less than 21 years old
4. Karnofsky/Lansky score of 60% or greater
5. Patients must have an ANC greater than or equal to 500/µl, platelet count greater than or equal to 20,000/µl. Patients may be transfused to obtain a platelet count greater than or equal to 20,000/µl.
6. Pulse Ox greater than or equal to 90% on room air
7. Serum AST less than 3 times the upper limit of normal
8. Total Bilirubin less than 1.5 times the upper limit of normal
9. Creatinine \< 1.5 times the upper limit of normal
10. Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria and expected to tolerate lymphodepletion).
11. Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies
12. Patients must have autologous transduced NKTs with greater than or equal to 20% expression of GD2-specific CAR.
13. Informed consent and assent (as applicable) obtained from parent/guardian and child.
14. Weight greater than 12kg
15. Negative QuantiFERON-TB or T-SPOT testing within 3 months prior to the start of LD

Treatment Exclusion Criteria:

1. Rapidly progressive disease
2. Currently receiving any investigational drugs
3. History or hypersensitivity to murine protein-containing products
4. Cardiomegaly or bilateral pulmonary infiltrates on chest radiograph or CT. However, patients with cardiomegaly on imaging may be enrolled if they have an assessment of cardiac function (i.e., ECHO or MUGA) within 3 weeks of starting protocol therapy that is within normal limits. Additionally, patients with bilateral pulmonary infiltrates on imaging may be enrolled if the lesions are not consistent with active neuroblastoma (i.e., negative on functional imaging with PET or MIBG, or by pathologic assessment).
5. Tumor potentially causing airway obstruction
6. Pregnancy or lactation or not willing to use birth control
7. Currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine
8. Severe previous toxicity form cyclophosphamide or fludarabine based on the enrolling physician's assessment
9. HIV infection
10. History of hypersensitivity, anaphylaxis, and/or adverse event with Etanercept

Where this trial is running

Houston, Texas

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

Study contacts

• Principal investigator: Gengwen Tian, MD — Baylor College of Medicine
• Study coordinator: Gengwen Tian, MD

Conditions Neuroblastoma; Natural Killer T-Cells; Chimerical Antigen Receptor