Clinical Research Directory

Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma

This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim work when combined with chemotherapy in patients with high-risk neuroblastoma. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Sargramostim helps the body produce normal infection-fighting white blood cells. These cells also help the dinutuximab work better. Giving chemotherapy before a stem cell transplant, with drugs such as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan, etoposide, carboplatin, topotecan, and isotretinoin, helps kill cancer cells that are in the body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells). Giving dinutuximab and sargramostim with combination chemotherapy may work better than combination chemotherapy alone in treating patients with high-risk neuroblastoma.

An Investigational Scan (68Ga-DOTATATE PET/CT) in Diagnosing Pediatric Metastatic Neuroendocrine Tumors

This trial studies how well an investigational scan called 68Ga-DOTATATE PET/CT works in diagnosing pediatric patients with neuroendocrine tumors that have spread to other places in the body (metastatic). A neuroendocrine tumor is an abnormal growth of neuroendocrine cells, which are cells resembling nerve cells and hormone-producing cells. 68Ga-DOTATATE is a radioactive substance called a radiotracer that when used with PET/CT scans, may work better than standard of care MIBG scans in diagnosing pediatric metastatic neuroendocrine tumors and targeting them with radiation therapy.

Dual-Target GD2/B7-H3 CAR-NK Cells for Pediatric Relapsed or Refractory Neuroblastoma

This illustrative Phase 1/Phase 2 study tests allogeneic dual-target GD2/B7-H3 (CD276) CAR-NK cells in children and young adults with relapsed or refractory neuroblastoma. After lymphodepletion, participants receive IV CAR-NK cells;Part A defines the RP2D and Part B estimates preliminary activity

Comparing 123I-MIBG and 18F-MFBG Imaging in Patients With Newly Diagnosed, High Risk Neuroblastoma

This phase II trial evaluates whether an investigational scan (18F-MFBG positron emission tomography \[PET\]/computed tomography \[CT\] or PET/magnetic resonance imaging \[MRI\]) can accurately detect tumors in patients with newly diagnosed, high-risk neuroblastoma as well as standard of care imaging with 123 I-MIBG. 18F-MFBG is a radioactive diagnostic agent that is injected into a vein and taken up by tumor cells. The cells can then be visualized using PET/CT or PET/MRI scans. A PET scan uses radioactive material injected into the blood to show the internal workings of the body. A CT scan uses x-rays and a computer to produce a 3-dimensional image of the body. MRI uses radiofrequency waves and a strong magnetic field rather than x-rays to provide clear and detailed pictures of internal organs and tissues. Combining PET with CT or MRI may help doctors better understand the extent and the exact location of disease. Diagnostic procedures, such as 18F-MFBG PET/CT or PET/MRI, may detect tumors as well as or better than the current standard imaging with 123 I-MIBG in patients with newly diagnosed, high-risk neuroblastoma.

Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)

This phase III trial studies iobenguane I-131 or lorlatinib and standard therapy in treating younger patients with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma. Radioactive drugs, such as iobenguane I-131, may carry radiation directly to tumor cells and not harm normal cells. Lorlatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or lorlatinib and standard therapy may work better compared to lorlatinib and standard therapy alone in treating younger patients with neuroblastoma or ganglioneuroblastoma.

Chemoimmunotherapy Combined With Autologous NK Cell Therapy for Pediatric Patients With Refractory and Relapsed High-Risk Neuroblastoma and Ganglioneuroblastoma

Neuroblastoma (NB) is a malignant neoplasm of the sympathetic nervous system, occurring in 1 in 8,000 live births, accounting for 6-10% of all childhood malignant neoplasms and responsible for 12-15% of mortality -, making it the most common and life-threatening extracranial tumor in childhood. Patients with stage 4 high-risk NB is the subgroup with the poorest prognosis. Within this group, two subgroups with an extremely unfavorable disease course are distinguished: patients with a poor response to the induction phase of therapy (refractory disease) and patients with relapsed or progressive disease. Nowadays, 10-15% of patients show a poor end-induction response, whereas achieving a good end-induction response associated with better long-term survival. Improvement of the response to induction therapy may contribute to better treatment outcomes in newly diagnosed high-risk NB patients and can be achieved by intensification of the induction phase to decrease the number of patients with refractory disease. Also intensification of the second-line therapy may contribute to better responses in patients with relapsed and progressive disease. Protocol aimed to overcome heterogeneous tumor drug resistance through the synergistic interaction of cytostatic and immunobiological agents in combination with NK cell therapy. This approach combines cytotoxic agents with anti-GD2 monoclonal antibodies (mAb) to enhance antitumor activity. Cultured, ex vivo-activated autologous NK cells are infused to compensate for effector cell depletion during therapy and to augment antibody-dependent cellular cytotoxicity (ADCC), potentially improving clinical outcomes. This comprehensive approach opens novel prospects for enhancing treatment efficacy in patients with refractory and relapsed high-risk NB. The expected outcomes of this protocol include a significant increase in therapeutic efficacy indicators - objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and relapse-free survival (RFS), as well as in patient quality of life.

Phase II Study of Proton Radiation Therapy for Neuroblastoma

This research study is evaluating a therapy called proton beam radiation therapy (PBRT) as a possible treatment for neuroblastoma. Neuroblastoma most commonly occurs in and around the adrenal glands, which are located at the top of the kidneys. However, it can also occur in other areas where groups of nerve cells exist, such as other areas of the abdomen, neck and near the spine. Conventional radiation therapy with photons is used as standard treatment for many patients with neuroblastic tumors. In this research study, the investigators are looking at another type of radiation called proton radiation which is known to spare surrounding tissues and organs from unnecessary radiation. Proton radiation delivers radiation to the area requiring radiation. This may reduce side effects that patients would normally experience with standard radiation therapy or other means of delivering proton radiation therapy. In this research study, the investigators are evaluating the effectiveness of using proton radiation delivered to reduce side effects associated with radiation treatment. The investigators will also be assessing the late side effects experienced by participants in each treatment group.

Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma

This phase III trial studies how well response and biology-based risk factor-guided therapy works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may not need treatment until it progresses. In this case, observation may be sufficient. Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and what the best treatment is. Response and biology-based risk factor-guided therapy may be effective in treating patients with non-high risk neuroblastoma and may help to avoid some of the risks and side effects related to standard treatment.

Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma

This research trial studies biomarkers in tumor tissue samples from patients with newly diagnosed neuroblastoma or ganglioneuroblastoma. Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.

SIOPEN BIOPORTAL, An International Registry Linked to a Virtual Biobank for Patients With Peripheral Neuroblastic Tumours

The SIOPEN BIOPORTAL is a prospective non-therapeutic multi-centre international study aimed at developing an international Registry linked to a Virtual Biobank for all the patients with peripheral neuroblastic tumor within countries of the SIOPEN network. The overall aim of this study is to provide a GDPR-compliant framework to collect basic clinical annotations, biological and genetic features and information about the location on biospecimens for all the patients with a peripheral neuroblastic tumor including neuroblastoma, ganglioneuroblastoma and ganglioneuroma in the SIOPEN network. This study will support data and sample management and intensify cross-borders data and sample sharing fostering translational and clinical research. The post-hoc hypothesis formulated based on the data generated in this study will be used as statistical basis for future precision medicine programs based on improved biological characterization, patient stratification and therapeutic management.

Engineered Neuroblastoma Cellular Immunotherapy (ENCIT)-01

Patients with recurrent or refractory neuroblastoma are resistance to conventional chemotherapy. For this reason, the investigators are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a chimeric antigen receptor (CAR). The CAR enables the T cell to recognize and kill the neuroblastoma cell through the recognition of CD171, a protein expressed of the surface of the neuroblastoma cell in patients with neuroblastoma. This is a phase 1 study designed to determine the maximum tolerated dose of the CAR+ T cells.

Abdominal Neuroblastoma Laparoscopic Surgery Risk Factors Stratification

Surgery plays significant role in treatment of neurogenic tumors, both for benign ganglioneuroma and for high risk neuroblastoma. The world literature has accumulated large experience in laparoscopic surgery for abdominal neuroblastoma. The presence of IDRF (image-defined risk factors) and tumor size (\>4-7 cm) are considered as common contraindications for minimally invasive surgery in neuroblastoma. However, the recent studies have shown that presence of IDRF is not an absolute contraindication for laparoscopic surgery. This open-label, nonrandomized, observational, phase III evaluates role and weight of different surgical risk factors (including IDRF, tumor size, tumor localization, tumor volume/patient height ratio, previous open surgical procedures, previous chemotherapy etc.) in the laparoscopic neuroblastoma resections. The aim of this study is to create novel risk factors scoring system for laparoscopic surgery in abdominal neuroblastoma.

Induction Chemoimmunotherapy for Patients With High-risk Neuroblastoma

The modern strategy of therapy of high-risk neuroblastoma, stage 4, consists of three phases - induction, consolidation and post- consolidation. Still current approaches demonstrates insufficient levels of ORR (overall response rate), OS (overall survival) and EFS (event free survival). NB-HR-2023 (neuroblastoma high risk) protocol aimed to investigate tolerability and toxicity and potential improvement of ORR, OS and EFS by overcoming of tumor heterogeneous drug resistance using the synergistic interaction of cytostatic and immunobiological agents in the induction. Protocol include the combination of standard chemotherapy (N5 and N6) with anti-GD2 MAB, which is potentially expected to improve outcomes in patients with high-risk neuroblastoma and ganglioneuroblastoma, 4th stage older 18 months. Currently, treatment with combinations of cytostatics with immunobiological agents is limited due to the risk of complications, which, nevertheless, is controlled with proper monitoring and concomitant therapy. Still no data about use of combination of standard chemotherapy (N5 and N6) with ch14.18/CHO MAB (dinutuximab beta) in induction in primary patients with neuroblastoma. Prospective, interventional trial include patients with neuroblastoma and ganglioneuroblastoma, 4th stage of the high-risk group older 18 months, who will receive combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB. Consolidation and post consolidation chemotherapy courses are not the subjects for analysis. Patients with high-risk neuroblastoma and ganglioneuroblastoma, stage 4, older 18 months who receive combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB at the Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology Delayed surgery (if needed) will be done after the 4th or 6th course of induction therapy and stem cells apheresis after the 2nd-5th course of induction therapy.