Clinical Research Directory

131I-Labeled MIBG for Refractory Neuroblastoma: A Compassionate Use Protocol

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

Comprehensive Omics Analysis of Pediatric and Adult Solid Tumors and Establishment of a Repository for Related Biological Studies

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.

N10: A Study of Reduced Chemotherapy and Monoclonal Antibody (mAb)-Based Therapy in Children With Neuroblastoma

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

NANT 2021-01 Phase II STING (Sequential Temozolomide, Irinotecan, NK Cells and GD2 mAb) Trial

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

Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma

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.

Phase I Trial of rhIL-15 Plus Dinutuximab Plus Irinotecan/Temozolomide for Children and Young Adults With Relapsed/Refractory Neuroblastoma

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.

Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children < 6 Years, Post Consolidation

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.

Feasibility Study of Prolonged Administration of Naxitamab, Irinotecan, and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma

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)

Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma

Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.

Prospective Comprehensive Molecular Analysis of Endocrine Neoplasms

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.

Open-Label Study of 18F-mFBG for Imaging Neuroblastoma

This is a Phase 3 study evaluating the positron-emitting radiopharmaceutical 18F-mFBG as an imaging agent for confirming or excluding the presence of neuroblastoma

Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors

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

PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy

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)).

Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas

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

Naxitamab Added to Induction for Newly Diagnosed High-Risk Neuroblastoma

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.

A Study of a Vaccine in Combination With β-glucan and GM-CSF in People With Neuroblastoma

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.

Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors

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.

4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma

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.

Familial Investigations of Childhood Cancer Predisposition

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.

18F-Fluorodopamine PET Studies of Neuroblastoma and Pheochromocytoma

PET (positron emission tomography) scans combined with a radioactive tracer will be used to identify and analyze tumors. Currently, the most common tracer used to analyze neuroblastoma tumors is called 123I-mIBG. However, the picture it provides is not always clear enough to see the very small areas of the disease. 18F-DA (18F-fluorodopamine) has been shown to be safe and more effective than 123I-mIBG in analyzing the tumor pheochromocytoma, which is closely related to neuroblastoma. With this research study, the investigators plan to meet the following goals: * Investigate to see if 18F-DA is safe to administer to pediatric patients with known or suspected neuroblastoma or pheochromocytoma * Examine where in the body 18F-DA goes. * Obtain information comparing 18F-DA to 123I-mIBG to see if 18F-DA could replace 123I-mIBG in the future. About 20 people, with known or suspected neuroblastoma or pheochromocytoma, will take part in this Pilot study at St. Jude.

Methionine PET/CT Studies In Patients With Cancer

The purpose of this study is to test the usefulness of imaging with radiolabeled methionine in the evaluation of children and young adults with tumor(s). Methionine is a naturally occurring essential amino acid. It is crucial for the formation of proteins. When labeled with carbon-11 (C-11), a radioactive isotope of the naturally occurring carbon-12, the distribution of methionine can be determined noninvasively using a PET (positron emission tomography) camera. C-11 methionine (MET) has been shown valuable in the monitoring of a large number of neoplasms. Since C-11 has a short half life (20 minutes), MET must be produced in a facility very close to its intended use. Thus, it is not widely available and is produced only at select institutions with access to a cyclotron and PET chemistry facility. With the new availability of short lived tracers produced by its PET chemistry unit, St. Jude Children's Research Hospital (St. Jude) is one of only a few facilities with the capabilities and interests to evaluate the utility of PET scanning in the detection of tumors, evaluation of response to therapy, and distinction of residual tumor from scar tissue in patients who have completed therapy. The investigators propose to examine the biodistribution of MET in patients with malignant solid neoplasms, with emphasis on central nervous system (CNS) tumors and sarcomas. This project introduces a new diagnostic test for the noninvasive evaluation of neoplasms in pediatric oncology. Although not the primary purpose of this proposal, the investigators anticipate that MET studies will provide useful clinical information for the management of patients with malignant neoplasms.

A Study of Avutometinib for People With Solid Tumor Cancers

The purpose of this study is to find out whether avutometinib is a safe treatment for advanced or recurrent solid tumor cancers in children and young adults. Researchers will look for the highest dose of avutometinib that is safe and cause few or mild side effects.

Naxitamab for High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow

Children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow will be treated for up to 101 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (GM-CSF). Patients will be followed for up to five years after first dose. Naxitamab, also known as hu3F8 is a humanised monoclonal antibody targeting GD2

Neuroblastoma Maintenance Therapy Trial

Difluoromethylornithine (DFMO) will be used in an open label, single agent, multicenter, study for patients with neuroblastoma in remission. In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. This study will focus on the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to prevent recurrence.