How Clinical Trials Are Saving the Lives of Children with Neuroblastoma

Neuroblastoma is the most common pediatric malignancy, accounting for almost 10% of childhood cancers, mostly in children under fice years old. Of the 700 to 800 cases diagnosed in the U.S. annually, up to 20% are seen by the Neuroblastoma Program at Texas Children’s Cancer and Hematology Center. The program comprises a subspecialized team of pediatric oncologists, pediatric surgical oncologists, radiation oncologists, pathologists, and geneticists — all dedicated solely to the care of neuroblastoma patients. 

Clinical trials paving the way 

As one of the largest such programs in the nation, Texas Children’s offers not only a highly specialized clinical team, but also a robust research and clinical trials program that offers access to trials available at only a handful of pediatric cancer centers.

While children with low- and intermediate-risk neuroblastoma have cure rates of over 90%, approximately 40% of children with neuroblastoma have "high-risk" tumors with much lower survival rates, despite aggressive treatment with combinations of chemotherapy, stem cell transplantation, surgery, radiation therapy, and immunotherapy. Cases of high-risk neuroblastoma are also associated with high rates of recurrence and tumors that are resistant to treatment. Because relapsed and refractory cases are so common, bringing novel therapy options into early- phase clinical trials is particularly important. 

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“We see all stages of neuroblastoma cases,” said Jennifer Foster, MD, MPH, Director of the Solid Tumor Programs, Clinical Director of the Neuroblastoma Program, and Associate Director of the Developmental Therapeutics Program at Texas Children’s. “We have a very large clinical trial program, especially for patients whose disease doesn’t respond to frontline therapy in the way we’d like it to.” 

One focus of the Neuroblastoma Program is leveraging expertise through several initiatives within Texas Children’s Cancer Centers, including the Center for Advanced Innate Cell Therapy (AICT), Center for Cell and Gene Therapy (CAGT), and Developmental Therapeutics Program. Within the last several years, the AICT team has developed protocols for clinical scale manufacturing of natural killer T (NKT) cells engineered with chimeric antigen receptors (CAR) — leveraging the body’s own immune system, as well as modern tools of synthetic biology to target and fight neuroblastoma cells. AICT’s optimized second-generation CAR construct recognizes GD2, a substance found on almost all neuroblastoma cells and this is the first clinical trial to test CAR NKT cells in humans. The goal of this phase 1 trial is to evaluate the safety and therapeutic activity of this GD2-specific CAR for targeting neuroblastoma. Preliminary results demonstrate that the therapy is well tolerated and produces anti-tumor activity in neuroblastoma patients.  

Another such study, GAIL-N — developed by CAGT scientists and exclusively available at Texas Children’s — also expands on previous research on GD2-specific CARs. This trial uses an engineered cytokine gene developed at our center, called C7R, to help neuroblastoma targeting T cells survive longer. Enabling CAR T cells to expand and survive in the body helps them kill cancer cells more effectively. 

“Some trials we offer patients, such as the immunotherapy trials developed through our AICT and CAGT, are available only at Texas Children’s,” Dr. Foster said. “Others are only available at select pediatric oncology phase 1I centers around the nation such as ours. About a third of our high-risk patients are local; the other two-thirds travel from around the country and the world for these innovative therapies.” 

For patients who travel to Texas Children’s, financial resources are available to help defray costs for families. Because a large proportion of patients come from outside Texas, the team is accustomed to working hand-in-hand with referring physicians, maintaining open communication after each visit and therapy.

“Our goal is to ensure seamless care here and when the patient returns home,” Dr. Foster said. 

I-131MIBG treatment 

Additionally, Texas Children’s offers clinical trials utilizing I-131MIBG therapy for patients with high-risk relapsed or refractory neuroblastoma. I-131 MIBG is a specialized therapy available at fewer than 20 centers in the nation. Metaiodobenzylguanidine (MIBG) is a substance absorbed by neuroblastoma cells. Combining MIBG with radioactive iodine (I-131) kills tumor cells via radiation emitted by the iodine, while sparing tissue that does not absorb MIBG. This specialized therapy is safe and used to treat patients with both newly diagnosed, as well as relapsed neuroblastoma.  

Ongoing research priorities 

Future research by the scientists in the Neuroblastoma Program will continue to explore new pathways, targets, and treatments in order to provide the most appropriate and most effective therapy for every child with neuroblastoma. 

To consult with the Neuroblastoma Program, learn more about how to refer a patient. Any child or young adult (21 years of age or younger) with neuroblastoma can be referred.