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 optimal patient care.

The Neuroblastoma Program offers its patients newly delevoped therapies targeted at neuroblastoma cells as well as those normal cells that can support tumor cell growth. These therapies offer families more options for treating their child’s cancer. CHLA is home to the New Approaches to Neuroblastoma Therapy (NANT) multi-institute consortium, which develops clinical 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 children with non-high risk neuroblastoma have better than 95% survival, half of children are diagnosed with “high risk” neuroblastoma and have only 50% survival. Advances in the understanding of neuroblastoma biology have led to the identification of subgroups of patients which are then treated with therapies designed for that group.

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

Innovation

Our program is based on a strong interaction between laboratory and clinical physicians, who have developed several new therapies that subsequently became the standard of care for high-risk neuroblastoma. This has included the development of the CEM (carboplatin, etoposide, melphalan) regimen to ablate tumor-supporting myeloid cells followed by transplant of healthy stem cells that reconstitute the child's immune system, the elimination of total body irradiation from the transplant regimen, and the use of isotretinoin as maintenance therapy after transplant.

Our investigators have also developed a new test (the NB5 assay which determines the expression of five neuroblastoma-related genes) to quantify minimal residual tumor cells 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 immunotherapy with a patient’s own natural killer (NK) cells, a type of white blood cell that can attack tumor cells, lenalidomide, an agent that can stimulate a patient’s immune system to assist NK cells, a monoclonal antibody that has become a standard treatment for high-risk neuroblastoma, and a precision therapy approach that aims to identify abnormal genes and/or determine the presence of immune or inflammatory gene activity that may predict which 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 of potential treatments against neuroblastoma. NANT Trials are focused on patients with relapsed or treatment-refractory neuroblastoma after standard therapies fail. 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 mistakenly 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.

The consortium's 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 Children's Oncology Group (COG). NANT provides safety information and rationales that enable the COG to conduct larger Phase II and III randomized trials that aim to determine whether new therapies can improve patient outcome. NANT has a strong track record of transferring knowledge to the COG in support of 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, the 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 who have special expertise and/or innovative ideas about neuroblastoma therapy. Special members of the NANT may participate as individual investigators and also enter patients in a selected trial if their institution has Phase I capabilities.