Neuroblastoma

Patients will then be randomized at study entry to one of three treatment arms. Patients on Arm A will receive a single treatment course with 131I-MIBG with vorinostat. Patients on Arm B will receive a single treatment course with 131I-MIBG and dinutuximab. Patients on Arm C will receive a single treatment course with 131I-MIBG with dinutuximab + vorinostat. After this course of treatment, we will check to see your response and then check to see how you are doing over time. All patients may choose to proceed to a second course of the same treatment if they and their physician feel healthy enough to do so. Approximately 118 patients will be receiving therapy on this trial.

An open, non-randomized Phase Ib-II trial of dose-escalation and cohorts expansion to evaluate the safety, pharmacokinetic profile and initial efficacy of APG-115 alone or in combination with APG-2575 in the treatment of recurrent or refractory neuroblastoma or solid tumors.

This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.

Background: * Endocrine neoplasms (tumors) are among the fastest growing tumors in incidence in the United States. Furthermore, it is often difficult to distinguish between benign or malignant tumors in cancers of the thyroid, parathyroid, adrenal gland, and pancreas. More research is needed to improve detection and treatment options for patients who develop these kinds of cancer. * Researchers are interested in studying the molecular changes that are involved in endocrine cancer development and growth. To collect a sample of tumor specimens and healthy tissue for further study, researchers are specifically looking for samples from participants who are scheduled for surgery or biopsy on endocrine tumors. Objectives: \- To collect samples of precancerous, cancerous, and healthy tissue from individuals who are scheduled for surgery or biopsy of endocrine system tumors. Eligibility: \- Individuals who have a tumor in or around their thyroid, parathyroid, adrenal gland, pancreas, or any neuroendocrine tissue, and are scheduled for surgery at the National Institutes of Health Clinical Center. Design: * Participants in this study will provide blood and urine samples prior to surgery. * During the surgery or biopsy, pieces of the tumor or precancerous growth and pieces of normal tissue near to the tumor will be removed for ongoing and future research. The rest of the tumor or growth will be sent for analysis. * After surgery, participants will receive routine care until discharge, and doctors will discuss possible treatment options. If there is an appropriate NIH protocol, participants may choose to be treated at the NIH. * After discharge, participants will return to the clinic for a routine postoperative check about 6 weeks following the operation, and then may be followed yearly at the Clinical Center or by phone....

This is a phase I dose-escalation study to determine the safety and feasibility of autologous CAR-TA T cells (B7-H3 CAR+ T cells administered with DNR-PRAME Tumor Antigen-specific T cells) following lymphodepleting chemotherapy in participants with relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma and Wilms tumor. Patients will be enrolled to one of three planned dose levels with B7-H3 CAR T cell dose determined based on the percentage of B7-H3 transduced cells (B7-H3+ population of cells), and dTBRII-transduced PRAME TA-specific T cell dose based on the total cell population. Both doses will be based on the recipient's body weight and combined in a 1:1 ratio. The safety of the CAR-TA T cell product will be evaluated and the maximum tolerated dose (MTD) will be determined. The safety endpoint will be assessed by monitoring for dose limiting toxicities for 28 days following CAR-TA T cell administration.

The purpose of this study is to evaluate the investigational oral drug AMXT 1501 in combination with oral eflornithine (DFMO). An investigational drug is one that has not been approved by the U.S. Food \& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat. The goals of this part of the study are: * Establish a recommended dose of AMXT 1501 in combination with DFMO * Test the safety and tolerability of AMXT 1501 in combination with DFMO * To determine the activity of study treatments chosen based on: * How each subject responds to the study treatment * How long a subject lives without their disease returning/progressing

This is a prospective, multicenter clinical trial in subjects with newly diagnosed high-risk neuroblastoma to evaluate the efficacy and safety of administering naxitamab with standard induction therapy. The initial chemotherapy will include 5 cycles of multi-agent chemotherapy. Naxitamab will be added to all 5 Induction cycles. We hypothesize that the addition of anti-GD2 therapy to induction chemotherapy will result in improved end of induction responses and improved survival.

The purpose of the study is to explore the combination of a bivalent vaccine, a sugar called beta-glucan (β-glucan), and a protein called granulocyte-macrophage colony stimulating factor (GM-CSF) as an effective treatment for people with high-risk neuroblastoma that is in complete remission. The combination may be effective because the different parts of the treatment work to strengthen the immune system's response against cancer cells in different ways.

This is an expanded access protocol/compassionate use single institution study designed to determine the palliative benefit and toxicity of 131I-MIBG in patients with progressive neuroblastoma and metastatic pheochromocytoma who are not eligible for therapies of higher priority. Response rate, toxicity, and time to progression and death will be evaluated.

Background: \- Laboratory investigators who are studying common childhood cancers are interested in developing a tissue repository to collect and store blood, serum, tissue, urine, or tumors of children who have cancer or adults who have common childhood cancers. To develop this repository, additional samples will be collected from children and adults who have been diagnosed with common childhood cancers such as leukemia and tumors of the central nervous system. Objectives: \- To collect and store blood, serum, tissue, urine, or tumor samples of children who have cancer or adults who have common childhood cancers. Eligibility: * Individuals who have been diagnosed with a common childhood cancer (e.g., leukemia) regardless of patient age. * Children, adolescents, and adults who have been diagnosed with a type of cancer more commonly found in adults. Design: * Extra blood, serum (the liquid part of blood), tissue, urine, or tumor samples will be collected from participants at a time when sampling is required for medical care or as part of a research study. * No additional procedures will be performed for the sole purpose of obtaining additional tumor tissue, aside from what is required for clinical care.

The purpose of this study is to test which treatment schedule of β-glucan with bivalent vaccine is more effective for participants with high-risk neuroblastoma that is in complete remission.

Substudy 01A is part of a platform study. The purpose of this study is to assess the efficacy and safety of zilovertamab vedotin in pediatric participants with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL)/Burkitt lymphoma, or neuroblastoma and in pediatric and young adult participants with Ewing sarcoma.

The purpose of this study is to find out whether N10 chemotherapy is a safe and effective treatment for children with high-risk neuroblastoma.

This is a compassionate use protocol to allow patients with advanced neuroblastoma palliative access to 131I-metaiodobenzylguanidine (131I-MIBG).

Background: Neuroblastoma is a type of cancer that causes tumors in nerves. It affects mainly infants and toddlers, and it causes about 15 percent of cancer-related deaths in children. Objective: To test a new drug (rhIL-15), combined with 3 standard cancer drugs, in people with neuroblastoma. Eligibility: People aged 3 to 35 years with neuroblastoma that did not respond or returned after standard treatment. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of their heart and lungs. They will have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle. Participants will be treated in 21-day cycles. They may have up to 4 treatment cycles. rhIL-15 is given through a needle into a vein over 5 to 7 days during the first week of each cycle. Participants will stay in the hospital while they are receiving the rhIL-15. Starting in the second week of the second cycle, participants will receive other drugs for treating cancer. They will have no study treatments during the third week of each cycle. Participants will visit the clinic at least 2 times a week throughout all 4 treatment cycles. They will have a physical exam and blood tests during these visits. Imaging scans, bone marrow biopsy, and other tests will be repeated at the end of cycles 2 and 4. Participants will have a follow-up visit 6 months after treatment ends. This visit will include a physical exam with blood and urine tests.

This is a phase II study looking at patient response to treatment with the combination dinutuximab, temozolomide, irinotecan, and GM-CSF.

This research is being done to investigate a treatment regimen of Irinotecan, Temozolomide, and Sargramostin, and an immunotherapy called Naxitamab and whether giving Naxitamab more slowly reduces the side effects for participants with relapsed or refractory neuroblastoma. The name of the study drugs involved in this study are: * Naxitamab (A type of monoclonal antibody) * Irinotecan (A standard of care chemotherapy) * Temozolomide (A standard of care chemotherapy) * Sargramostim (A standard of care, granulocyte-macrophage colony stimulating factor)

Pilot study to determine feasibility of adding intrathecal chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age.

The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid tumors. An investigational drug is one that has not been approved by the U.S. Food \& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat. The goals of this part of the study are: * Establish a recommended dose of silmitasertib in combination with chemotherapy * Test the safety and tolerability of silmitasertib in combination with chemotherapy in subjects with cancer * To determine the activity of study treatments chosen based on: * How each subject responds to the study treatment * How long a subject lives without their disease returning/progressing

A Phase I open-label, multicenter study, to evaluate the safety, feasibility, and maximum tolerated dose (MTD) of treating children with newly diagnosed DIPG or recurrent neuroblastoma with molecular targeted therapy in combination with adoptive cell therapy (Total tumor mRNA-pulsed autologous Dendritic Cells (DCs) (TTRNA-DCs), Tumor-specific ex vivo expanded autologous lymphocyte transfer (TTRNA-xALT) and Autologous G-CSF mobilized Hematopoietic Stem Cells (HSCs)).

Hematopoietic stem cell transplantation can cure patients with blood cancer and other underlying diseases. αβ-T cell and B cell depletion has been introduced to decrease GVHD and PTLD and has demonstrated effectiveness for hematologic malignancies and non-malignant diseases additionally increasing the donor pool as to allow for haploidentical transplant to safely occur. While solid tumors can be highly chemotherapy sensitive, many remain resistant and require multimodalities of treatment. Immunotherapy has been developed to harness the immune system in fighting solid tumors, though not all have targeted effects. Some solid tumors are treated with autologous transplants; however, they do not always demonstrate an improved event free survival or overall survival. There has been evidence of the use of allogeneic stem cell transplants to provide a graft versus tumor effect, though studies remain limited. By utilizing αβ-T cell and B cell depletion for stem cell transplants and combining with zoledronic acid, the immune system may potentially be harnessed and enhanced to provide an improved graft versus tumor effect in relapsed/refractory solid tumors and promote an improved event-free survival and overall survival. This study will investigate the safety of treatment with a stem cell graft depleted of αβ-T cell and CD19+ B cells in combination with zoledronic acid in pediatric and young adult patients with select solid tumors, as well as whether this treatment improves survival rates in these patients.

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multiple 4SCAR-T cell therapy which targets GD2, PSMA and CD276 surface antigens in patients with relapsed and refractory neuroblastoma (NB). Another goal of the study is to understand the function of the multi-CAR-T cells and their persistency in the patients.

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown in the Eligibility Section, you may enroll regardless of the results of your clinical genetic testing. While it is well recognized that hereditary factors contribute to the development of a subset of human cancers, the cause for many cancers remains unknown. The application of next generation sequencing (NGS) technologies has expanded knowledge in the field of hereditary cancer predisposition. Currently, more than 100 cancer predisposing genes have been identified, and it is now estimated that approximately 10% of all cancer patients have an underlying genetic predisposition. The purpose of this protocol is to identify novel cancer predisposing genes and/or genetic variants. For this study, the investigators will establish a Data Registry linked to a Repository of biological samples. Health information, blood samples and occasionally leftover tumor samples will be collected from individuals with familial cancer. The investigators will use NGS approaches to find changes in genes that may be important in the development of familial cancer. The information gained from this study may provide new and better ways to diagnose and care for people with hereditary cancer. PRIMARY OBJECTIVE: * Establish a registry of families with clustering of cancer in which clinical data are linked to a repository of cryopreserved blood cells, germline DNA, and tumor tissues from the proband and other family members. SECONDARY OBJECTIVE: * Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.

The goal of this study is to demonstrate that cytokine-induced memory-like natural killer cells (CIML-NK cells) can be generated from donor cells and infused safely into patients with relapsed or refractory neuroblastoma during dinutuximab-based therapy.

The purpose of this research study is to find how active and safe 131 I-MIBG is in patients with resistant neuroblastoma, malignant pheochromocytoma and malignant paraganglioma.