Investigator-initiated and Industry-sponsored Trials
Our team has strived to bring innovative clinical trials to UW-AFCH, many of which are based on the translational research conducted by our faculty. Our investigator-initiated clinical research is focused on two main areas, immunotherapy and molecular targeted radiotherapy. We developed a first-in-human trial for children with relapsed neuroblastoma and osteogenic sarcoma, which utilized ex-vivo activated/expanded haploidentical NK cells administered in combination with hu14.18-IL2, an anti-GD2 immunocytokine.
University of Wisconsin Team Develops Novel Strategy for High-Risk Neuroblastoma
We are currently working on a successor trial for which we will generate ex-vivo expanded, haploidentical memory-like NK cells, and infuse them together with an anti-GD2 mAb. To our knowledge, this immunotherapy strategy has not previously been explored to treat children with GD2+ malignancies.
Another novel approach developed at UW-AFCH to treat children with relapsed solid tumors utilizes TCR-αβ+ and CD19+ depleted haploidentical hematopoietic stem cell transplantation. Use of haploidentical (parental) stem cell grafts ensures that virtually all children will have a suitable donor, and the T cell depletion methodology allows for administration of alloreactive NK and γδ T cells at the time of transplant. Patients enrolled on this trial also receive infusions of zoledronic acid post-transplant to augment immune-mediated tumor eradication.
We established AFCH as an 131I-MIBG treatment center in 2007, one of only 12 such centers in the country at the time. This has allowed our program to administer therapeutic doses of 131I-MIBG, as well as other targeted radiotherapeutic agents.
Our team is collaborating with 2 European centers on a phase I/II clinical trial that combines 131I-MIBG therapy with immunotherapy utilizing dinutuximab beta (anti-GD2) and nivolumab (anti-PD1) to treat children with relapsed or refractory neuroblastoma. This novel trial is based on pre-clinical research conducted by our faculty, and other UW investigators.
This Week in Pediatric Oncology #26 – Killer Immunoglobulin Receptor (KIR) Mismatch in Neuroblastoma
We are also participating in an industry-sponsored phase 1 trial utilizing a compound developed at UW known as CLR 131. CLR is a phospholipid ether that accumulates in lipid rafts, which are cell wall structures present in higher concentrations in tumors compared to normal tissues. The CLR is labeled with I-131 and selectively accumulates in a wide variety of pediatric malignancies. This trial is open to children with relapsed brain tumors and non-CNS solid tumors. We are involved with another industry-sponsored limited institution trial exploring the use of 67Cu-SARTATE to treat patients with relapsed/refractory neuroblastoma. 67Cu-SARTATE is a somatostatin analogue and gains entrance into neuroblastoma cells via their SSTR2 receptors.
Consortium Trials
We also conduct numerous clinical trials through many different clinical research consortia. These include the Children’s Oncology Group (COG), the Pediatric Transplant and Cell Therapy Consortium (PTCTC), the Primary Immune Deficiency Treatment Consortium (PIDTC), the Pediatric Cancer Immunotherapy Trials Network (Peds-CITN), the National Experimental Therapeutics (NEXT) consortium, the Midwest Area Research Consortium for Health (MARCH), and the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC).
Professor,
Interim BMT Director