Neuroblastoma Program

The Neuroblastoma Program at Children’s Hospital Los Angeles has a vision to provide advanced therapies to children to improve their survival rates and quality of life after receiving a diagnosis of neuroblastoma. The neuroblastoma team includes physicians, who are national and international leaders in neuroblastoma, with expertise in oncology, surgery, radiation therapy, pathology and radiology. Each of the providers collaborates closely to provide the optimal patient care.

The Neuroblastoma Program offers its patients many new therapies targeted at neuroblastoma cells and the normal cells that support tumor cell growth. These therapies offer families more options to treat their child’s cancer. CHLA is home to the New Approaches to Neuroblastoma Therapy (NANT), which develops many of these trials and brings a “bench-to-bedside” approach to our care. NANT is the only consortium in the world solely dedicated to developing novel treatments and biomarkers through early clinical trials (Phase I and II) for neuroblastoma.

What is neuroblastoma?

Neuroblastoma is the third most common cancer in children and the second most common solid tumor in children, besides brain tumors. This tumor has a diverse biology. Patients’ biologic characteristics are used to assign a “risk group” at diagnosis.  While non-high risk neuroblastoma has more than 95% survival, half of children present with widespread “high risk” neuroblastoma with only 50% survival. Advances in the understanding of neuroblastoma biology have led to identifying subgroups of patients which are then treated with therapies designed for that group.

For non-high risk patients, the focus is on decreasing therapy for biologically identified subgroups, while maintaining the excellent survival rates and decreasing possible late side effects. For high-risk neuroblastoma, the focus is on identifying novel therapies that have mechanisms relevant for neuroblastoma and that can improve patient outcome.

Innovation

Our program is based on the strong interaction of laboratory and clinical physicians, who have piloted several novel therapies, which subsequently became standard of care for high-risk neuroblastoma. This has included the development of the CEM (carboplatin, etoposide, melphalan) regimen for myeloablative transplant, the elimination of total body irradiation from the transplant regimen, and using isotretinoin as maintenance therapy after transplant.

Our investigators have also developed novel tests (NB5 assay which tests for the expression of five neuroblastoma related genes) to quantify minimal residual tumors not detectible by standard evaluations. The Neuroblastoma Program’s physicians are members of the Children’s Oncology Group (COG) Neuroblastoma committee, have chaired multiple COG national studies for neuroblastoma, and are active in the development of national COG studies for neuroblastoma. 

Current approaches in development include the novel methods to quantify minimal residual tumor to better define tumor response and patient prognosis, the novel immunotherapies with the patient’s own natural killer (NK) cells, a type of white blood cell that can attack tumor cells and the lenalidomide, an agent that can stimulate the patient’s immune system to be assist NK cells and/or the monoclonal antibody that is a standard treatment for high risk neuroblastoma, and the precision therapy which will try to  identify abnormal genes and/or determine the presence of immune or inflammatory gene activity that may predict what therapy will be most helpful for an individual patient.

NANT Consortium

What is NANT?

NANT is a group of 14 North American pediatric cancer centers with expertise in neuroblastoma who perform early (phase I and II) clinical trials based on laboratory data that demonstrates specific activity against neuroblastoma. NANT Trials are focused on patients with relapsed or refractory neuroblastoma after standard therapy fails. Established in 2000, NANT’s approach is to use laboratory models to identify novel agents that both target the cancer cells and their surrounding environment of normal cells that support tumor growth. 

How does NANT work?

NANT brings together a multidisciplinary team of more than 75 laboratory and clinical scientists with complementary expertise in genetics, biology, immunology, pathology, biostatistics, clinical investigations, and imaging all with a single focus on finding better treatments for children with high-risk neuroblastoma. Since its beginning, NANT has treated more than 600 children  with neuroblastoma in multiple clinical trials.

NANT expertise includes detailed pharmacokinetics, biologic correlates, and administration of complex therapies to establish feasibility and safety. NANT investigators have a proven record of moving innovative approaches into standard frontline therapy for high-risk neuroblastoma. Our NANT Biology study established a valuable repository for relapsed and refractory tumor tissue, BM tumor cells, blood, and radiology images. This unique resource is available to the larger NB research community.

NANT closely interacts and collaborates with the COG. NANT provides data to COG that is critical to provide the rationale and safety information for COG to conduct larger Phase II and III randomized trials that will confirm if these novel therapies can improve patient outcome. NANT has a strong track record of transferring knowledge to COG both for therapeutic and biomarker studies.

A NANT Parent Advisory Committee provides parent input during the development of NANT clinical trials. The Committee includes parent coordinators for education, public website, fundraising, and coordination of local parent representatives at each NANT site.

NANT has created a "Guest Membership" designation to encourage collaboration with non-NANT investigators with innovative ideas for neuroblastoma therapy and with special expertise. Special members may participate as individual investigators, or if their institution has Phase I capabilities, also enter patients in that selected trial.