CAR T-Cell Therapy for Neuroblastoma and Osteosarcoma

A Phase I Study of Autologous Activated T-Cells Expressing a 2nd Generation GD2 Chimeric Antigen Receptor, IL-15, and iCaspase9 Safety Switch Administered To Patients With Relapsed/Refractory Neuroblastoma or Relapsed/Refractory Osteosarcoma

This study is testing a new CAR T-cell therapy for children with hard-to-treat neuroblastoma and osteosarcoma to see if it can better fight their cancer while keeping them safe from serious side effects.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Months and up
• Sex: All
• Sponsor: UNC Lineberger Comprehensive Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine, chimeric antigen receptor, CAR-T
• Locations: 2 sites (Atlanta, Georgia and 1 other locations)
• Trial ID: NCT03721068 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates a novel treatment combining CAR T-cells targeting GD2 with IL-15 and an off switch mechanism using iCaspase9 for patients with relapsed or refractory neuroblastoma and osteosarcoma. The approach aims to enhance the effectiveness of T-cells in recognizing and destroying cancer cells while providing a safety mechanism to mitigate severe side effects. Participants will undergo a preparatory regimen followed by the infusion of modified T-cells, with careful monitoring for efficacy and safety. The study is multicenter, involving collaboration with prominent cancer research institutions.

Who should consider this trial

Good fit: Ideal candidates are children with high-risk neuroblastoma or osteosarcoma that is persistent, refractory, or relapsed after standard treatments.

Not a fit: Patients with non-high-risk neuroblastoma or osteosarcoma, or those without histological confirmation of these conditions, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for children with difficult-to-treat neuroblastoma and osteosarcoma.

How similar studies have performed: Previous studies using CAR T-cell therapies have shown promise, indicating potential for success with this novel approach.

Eligibility criteria

All clinical and laboratory data required for determining eligibility must be available in the subject's medical/research record which will serve as the source document.

Because of the nature of iC9.GD2.CAR.IL-15 T cell product preparation, subjects will be assessed for initial study enrollment eligibility (prior to cell procurement) and then will have to meet criteria prior to starting lymphodepletion and prior to T cell infusion.

Inclusion Criteria for the Study:

1. Written HIPAA authorization signed by legal guardian.
2. Adequate performance status as defined by Lansky or Karnofsky performance status of ≥ 60 (Lansky for \<16 years of age).
3. Life expectancy ≥12 weeks.
4. Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. Bone marrow samples are acceptable as confirmation of neuroblastoma, confirmation of osteosarcoma at diagnosis
5. High-risk neuroblastoma with persistent/refractory or relapsed disease, defined as:

   1. First or greater relapse of neuroblastoma following completion of aggressive multi-drug frontline therapy.
   2. First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy. Persistent/refractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).
   3. Patients must be diagnosed with high risk neuroblastoma at initial diagnosis or if non-high risk at time of initial diagnosis must have had evidence of metastatic progression when \>18 months of age as defined in the protocol or relapsed or refractory osteosarcoma that is not responsive to standard treatment.
6. Measurable or evaluable disease per Revised INRC for subjects with neuroblastoma or measurable disease by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 criteria for subjects with osteosarcoma.
7. Adequate central nervous system function as defined by:

   1. No known Central Nervous System ( CNS) disease
   2. No seizure disorder requiring antiepileptic drug therapy

Exclusion Criteria for the Study Subjects meeting any of the following exclusion criteria will not be able to participate in this study (procurement, lymphodepletion, and cell infusion).

1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
2. Has a known additional malignancy that is active and/or progressive requiring treatment.
3. History of hypersensitivity reactions to murine protein-containing products.
4. History of hypersensitivity to cyclophosphamide or fludarabine.

Where this trial is running

Atlanta, Georgia and 1 other locations

• Emory - Winship Cancer Institute — Atlanta, Georgia, United States (Withdrawn)
• Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill — Chapel Hill, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: George Hucks, MD — UNC Lineberger Comprehensive Cancer Center

Conditions Neuroblastoma; Osteosarcoma; Autologous Chimeric Antigen Receptor T Cells; Interleukin-15; Disialoganglioside; Caspase 9; Pediatric; Rimiducid