Clinical Research Directory

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.

A Study of the Effect of Hu3F8/GM-CSF Immunotherapy Plus Isotretinoin in Patients in First Remission of High-Risk Neuroblastoma

The purpose of this study is to test see the combined effects of the study drug called Humanized 3F8 (Hu3F8) when used with granulocyte-macrophage colony stimulating factor (GM-CSF). Hu3F8 plus GM-CSF could prevent your neuroblastoma from growing, but it could also cause side effects.

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.

Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)

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.

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.

NK White Blood Cells and Interleukin in Children and Young Adults With Advanced Solid Tumors

BACKGROUND: * Despite progress, some children and young adults with solid tumors still experience poor survival. * Activated NK cells potently kill autologous pediatric solid tumors, and clinical grade procedures are available to generate large numbers of activated NK cells for adoptive cell therapy. OBJECTIVES: * Primary objectives are: 1) to assess the feasibility of harvesting and expanding activated NK cells to meet escalating dose goals in Cohort A, 2) to assess the toxicity of infusing escalating doses of activated NK cells following lymphodepleting chemotherapy without rhIL15 (cohort A), and 3) to assess the toxicity of infusing NK activated cells with escalating doses of rhIL15 (cohort B) in pediatric patients with refractory malignant solid tumors. * Secondary objectives are: 1) to identify biologically active doses of activated autologous NK cells plus or minus rhIL15 by monitoring changes in NK cell number, phenotype and function, 2) to assess pharmacokinetics and immunogenicity of rhIL15 in a pediatric population, and 3) assess antitumor effects and changes in FDG-PET following administration of activated NK cells to lymphopenic hosts plus or minus rhIL15. 4) to evaluate saftey and efficacy of subsequent cycles of autologous NK cell infusions in patients in cohort A who received benefit from the first NK cell infusion. ELIGIBILITY: * Patients in Cohort A: 2-29 years with with refractory pediatric malignant solid tumors, Patients in Cohort B: 2-25 years with refractory pediatric malignant solid tumors. * Adequate performance status and organ function, recovered from toxic effects of prior therapy, no requirement for systemic corticosteroids and no history of allogeneic stem cell transplantation. DESIGN: * All patients receive pre-NK lymphodepleting chemotherapy with cyclophosphamide. * Cohort A receives escalating doses of activated autologous NK cells to identify feasibility of generating cells and tolerability, and potentially identify an MTD. * A1: 1x10(6) NK cells/kg * A2: 1 x 10(7) NK cells/kg * A3: 1 x 10(8) NK cells/kg * If feasibility and acceptable toxicity is demonstrated for all doses in Cohort A, patients enrolled on cohort B will receive activated autologous NK cells plus escalating doses of rhIL15 using the following schema: * B1: 1 x 10(7) NK cells/kg + rhIL15 0.25 mcg/kg/d IV x 10 * B2: 1 x 10(7) NK cells/kg + rhIL15 0.5 mcg/kg/d IV x 10 * B3: 1 x 10(7) NK cells/kg + rhIL15 1 mcg/kg/d IV x 10 * B4: 1 x 10(7) NK cells/kg + rhIL15 2 mcg/kg/d IV x 10 * Three patients will be enrolled at each dose level, with the dose level expanded to 6 if dose-limiting toxicity occurs. An expanded group of 12 patients will be treated at the highest tolerable dose level. DLT toxicity monitoring will continue for 21 days after the NK infusion, or 14 days after the last rhIL15 dose in Cohort B (whichever is later).

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.

Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors

This phase I trial studies the safety of transplantation with a haploidentical donor peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with the immunomodulating drug, Zoledronate, given in the post-transplant period to treat pediatric patients with relapsed or refractory hematologic malignancies or high risk solid tumors.

Myeloablative Consolidation Therapy and Tandem Autologous Stem Cell Rescue in Patients With High-Risk Neuroblastoma

This is a phase II single center study to administer two courses of myeloablative consolidation chemotherapy each followed by an autologous peripheral blood stem cell (PBSC) rescue in patients with high-risk neuroblastoma who have completed induction chemotherapy (independent of this study). Ideally, patients should begin consolidation chemotherapy no later than 8 weeks after the start of Induction Cycle #5; however it is strongly recommended to begin consolidation within 4-6 weeks after the start of Induction Cycle #5.

International PPB/DICER1 Registry

PPB has strong genetic implications, with a unique set of conditions in an individual or their family, occurring mostly in childhood and adolescence. The International PPB/DICER1 Registry first reported DICER1 germline loss-of-function variations in individuals with PPB and their family members. Conditions associated with DICER1 include Sertoli-Leydig cell tumor (SLCT), gynandroblastoma, ovarian sarcoma, peritoneal PPB, lung cysts, renal cysts, cystic nephroma (CN), anaplastic sarcoma of the kidney (ASK), Wilms tumor, primary DICER1-associated central nervous system (CNS) sarcoma, pineoblastoma, pituitary blastoma, multinodular goiter, thyroid carcinoma, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma (CBME), juvenile hamartomatous intestinal polyps, embryonal rhabdomyosarcoma (ERMS) and undifferentiated sarcoma. DICER1 variations may also be associated with macrocephaly and overgrowth syndrome. The International PPB/DICER1 Registry estimates that 30-50 cases of Type I and Ir PPB and 40-60 cases of Types II and III PPB are diagnosed annually worldwide. In 2009, the International Pleuropulmonary Blastoma Registry began a prospective study to collect treatment data on individuals for whom therapy decisions were made by their treating institution.

A Patient Registry of Patients With High-risk Neuroblastoma Being Treated With the Monoclonal Antibody Dinutuximab Beta

This is a non-interventional, multi-national, observational, prospective patient registry to further evaluate the effectiveness and safety of dinutuximab beta - a monoclonal immunoglobulin G 1 (IgG1) antibody, to obtain information on survival, pain severity and incidence of neuro-toxicity, visual impairment, capillary leak syndrome, cardiovascular events, hypersensitivity reactions and long-term safety.

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.

Prospective Multicenter Study of the Genomic, Transcriptomic, and Biological Profile of Patients With Neuroblastoma

This is an investigator-initiated, multicenter, prospective, non-profit study. Patients who provide informed consent to participate will be asked to provide a peripheral blood sample, a fresh tumor tissue sample (obtained by biopsy), and/or a bone marrow sample. All patients with neuroblastoma at diagnosis, with relapsed disease, or with refractory disease may participate, provided that the diagnosis and disease status are established by the treating physician in accordance with national clinical practice and by the participating study center. Enrolled patients will be reported and registered by means of a paper-based notification form sent by email to the Coordinating Center, which will assign a unique identification code to each patient. At the time of notification, clinical and treatment-related data will be collected using a paper-based Case Report Form (CRF). Biological material (peripheral blood, bone marrow, and/or tumor biopsy samples) must be centralized at the Laboratory of Experimental Oncology Therapies, IRCCS Istituto Giannina Gaslini, Genoa, Italy, in accordance with the procedures described in the study protocol. Samples will be processed and analyzed as specified in the protocol. The results of the initial analysis performed at CEINGE, Naples, will be communicated by the CEINGE Laboratory to the Coordinating Center. A multidisciplinary meeting will then be held with a panel of experts, including oncologists, biologists, pharmacists, and infectious disease specialists. Following this meeting, an individual report will be prepared for each patient. The report will include the results of Whole Exome Sequencing (WES) or Cancer Gene Panel (CGP) analysis performed on the patient's DNA, together with any potential therapeutic recommendations based on the molecular alterations identified. The report will be sent to the physician responsible for the individual patient. For patients who provide additional consent by signing the appropriate informed consent form, biological material may also be used for the following purposes: i) Immunophenotyping, with particular focus on GD2 and B7-H3 expression in tumor biopsy samples and in neuroblastoma cells infiltrating the bone marrow; ii) High-throughput screening of libraries comprising readily available anticancer drugs; iii) Generation of in vitro and in vivo tumor models, including primary cell lines and spheroids in vitro, and murine models such as Patient-Derived Xenografts (PDX) and Cell Patient-Derived Xenografts (CPDX) at the Coordinating Center, as well as zebrafish models at San Martino-IST, Genoa, and/or Città della Speranza, Padua.

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.

A Study of a Vaccine in Combination With Beta-glucan in People With Neuroblastoma

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.

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.

Agnostic Therapy in Rare Solid Tumors

The ANTARES study is a phase II basket trial designed to evaluate the tissue-agnostic efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or metastatic rare tumors. The study aims to treat rare malignancies with PD-L1 expression (CPS ≥ 10), regardless of the tumor's tissue type or location. Patients who have not responded to standard treatments will be included, and treatment will last for up to 12 months. The study will assess objective response, progression-free survival, and biomarkers such as PD-L1, ctDNA, and microvesicles, in a multicenter collaborative effort to provide innovative therapeutic options for this underrepresented population

EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or refractory non-CNS solid tumors to evaluate the safety, feasibility, and efficacy of administering T cell products derived from the research participant's blood that have been genetically modified to express a EGFR-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express EGFR and the selection-suicide marker EGFRt. EGFRt is a protein incorporated into the cell with our EGFR receptor which is used to identify the modified T cells and can be used as a tag that allows for elimination of the modified T cells if needed. On Arm A of the study, research participants will receive EGFR-specific CAR T cells only. On Arm B of the study, research participants will receive CAR T cells directed at EGFR and CD19, a marker on the surface of B lymphocytes, following the hypothesis that CD19+ B cells serving in their normal role as antigen presenting cells to T cells will promote the expansion and persistence of the CAR T cells. The CD19 receptor harbors a different selection-suicide marker, HERtG. The primary objectives of the study will be to determine the feasibility of manufacturing the cell products, the safety of the T cell product infusion, to determine the maximum tolerated dose of the CAR T cells products, to describe the full toxicity profile of each product, and determine the persistence of the modified cell in the subject's body on each arm. Subjects will receive a single dose of T cells comprised of two different subtypes of T cells (CD4 and CD8 T cells) felt to benefit one another once administered to the research participants for improved potential therapeutic effect. The secondary objectives of this protocol are to study the number of modified cells in the patients and the duration they continue to be at detectable levels. The investigators will also quantitate anti-tumor efficacy on each arm. Subjects who experience significant and potentially life-threatening toxicities (other than clinically manageable toxicities related to T cells working, called cytokine release syndrome) will receive infusions of cetuximab (an antibody commercially available that targets EGFRt) or trastuzumab (an antibody commercially available that targets HER2tG) to assess the ability of the EGFRt on the T cells to be an effective suicide mechanism for the elimination of the transferred T cell products.

Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors

This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.

Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors

A study to learn about safety and find out maximum tolerable dose of palbociclib given in combination with chemotherapy (temozolomide with irinotecan or topotecan with cyclophosphamide) in children, adolescents and young adults with recurrent or refractory solid tumors (phase 1). Neuroblastoma tumor specific cohort to further evaluate antitumor activity of palbociclib in combination with topotecan and cyclophosphamide in children, adolescents, and young adults with recurrent or refractory neuroblastoma. Phase 2 to learn about the efficacy of palbociclib in combination with irinotecan and temozolomide when compared with irinotecan and temozolomide alone in the treatment of children, adolescents, and young adults with recurrent or refractory Ewing sarcoma (EWS).

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

Molecular Characterization of Neuroblastic Tumor: Correlation With Clinical Outcome

The purpose of this study is to find out the genetic and biochemical makeup of your neuroblastic tumor, which influences its aggressiveness and the suitable therapy. These research studies include surface marker analysis, cytogenetics, cancer genes,genome sequencing, tumor growth-related genes and tumor growth in test tubes. Your blood, marrow, and hematopoietic stem cell samples will also be tested for tumors or leukemia cells, and your serum tested for anti-tumor antibodies.

Allogeneic Tumor Cell Vaccination With Oral Metronomic Cytoxan in Patients With High-Risk Neuroblastoma

Neuroblastoma is the second most common solid tumor seen in children, but causes approximately 15% of childhood cancer deaths each year. Patients with high-risk disease require treatment with a combination of chemotherapy, surgery, radiation, and stem cell transplant; however, many will have their disease come back within 3 years. Due to this high rate of relapse, this study is being done to investigate an experimental treatment option for children whose disease has returned. This clinical trial is for patients with neuroblastoma that has either come back after treatment or never went away in the first place. A series of immunizations will be administered using a tumor vaccine and add low-dose chemotherapy to be taken by mouth on a daily basis. The hope is that the vaccine will cause the immune system to recognize and kill more types of neuroblastoma tumors. Additionally, the immunizations will be combined with daily low dose chemotherapy. Daily low-dose chemotherapy, also know as metronomic chemotherapy, works by attacking the blood vessels that allow tumors to grow. Using metronomic doses of a drug called cytoxan can also decrease T regulatory cells, a specific type of cell that tumors use to hide from the immune system. The purpose of this study is to test the safety and anti-tumor effect of the tumor cell vaccination plus low dose, metronomic chemotherapy in treating patients with relapsed/refractory neuroblastoma.

MCT for the Harvard/UCSF ROBIN Center

The goal of the Molecular Characterization Trial (MCT) is to obtain biological specimens and data resources from patients enrolled on prospective trials, to ensure that the Harvard/UCSF ROBIN Center accomplishes its key objective of advancing our understanding of the biological mechanisms that underlie how radiation treats tumors but also can cause unwanted side effects. The MCT focuses on collection of research biospecimens before, during, and after radiation. Also critical to the MCT is the deep annotation of these research biospecimens with elements that complement each other to provide a holistic, detailed view of each patient. Annotated elements include those used in the past such as clinical and biological features but extend to factors we have so far neglected but must incorporate in the future such as dosimetry (precise anatomical measurement of radiation dose), artificial intelligence, computational biology, and natural language processing.