First-in-Humans Clinical Trial to Treat Children with Relapsed Neuroblastoma Opens at American Family Children’s Hospital

Doctor looking through a microscope — Above, Kenneth DeSantes, MD in a research lab. DeSantes and Paul Sondel, MD, PhD are co-Principal Investigators on a pioneering first-in-humans clinical trial for children with relapsed or refractory neuroblastoma.

A first-in-humans clinical trial for children with relapsed or refractory neuroblastoma has opened at American Family Children’s Hospital (AFCH). Neuroblastoma is one of the most common solid tumors in children. Patients who are classified as “high-risk” (about 40 percent) have less than a 50 percent survival rate.

131I-MIBG, a type of molecular targeted radiotherapy, has been used for many years to treat children with relapsed neuroblastoma. AFCH is one of about 25 centers in the United States capable of providing this therapy. While the treatment is effective, it is not curative, so significant effort has been expended devising ways to improve the durability of responses achieved with this agent.

This trial, which initially opened in England, is investigating the combination of targeted radiation therapy with immunotherapy to treat children with relapsed or refractory neuroblastoma. The concept is based on laboratory work conducted at University of Wisconsin–Madison by Paul Sondel, MD, PhD (Professor and Research Director, Division of Hematology, Oncology & Bone Marrow Transplant) and Zachary Morris, MD, PhD (Department of Human Oncology). Sondel and Kenneth DeSantes, MD (Professor, Division of Pediatric Hematology, Oncology & Bone Marrow Transplant) are the trial’s co-Principal Investigators.

In a pre-clinical murine model, significant synergy was demonstrated between radiation therapy and immunotherapy. This trial, known as the “MiniVan” study, combines 131I-MIBG therapy with a monoclonal antibody that recognizes neuroblastoma and focuses the patients’ immune system on the cancer. A third drug, nivolumab, is utilized in order to prevent the tumor from shielding itself against the immunologic attack, thereby enhancing immune-mediated tumor destruction and improving the possibility of cure.

The UW Pediatric Hematology, Oncology and Bone Marrow Transplant program is collaborating with three other centers in Europe on this pioneering first-in-humans clinical trial. AFCH is the first and only center in the United States to offer this therapy.