B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults...
Pediatric Solid TumorGerm Cell Tumor15 moreThis 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 B7H3-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express B7H3. On Arm A of the study, research participants will receive B7H3-specific CAR T cells only. On Arm B of the study, research participants will receive CAR T cells directed at B7H3 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. Arm A CAR T cells include the protein EGFRt and Arm B CAR T cells include the protein HER2tG. These proteins can be used to both track and destroy the CAR T cells in case of undue toxicity. 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 participant's body on each arm. Participants 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. Participants 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.
Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors...
OsteosarcomaEwing Sarcoma8 moreThe is a phase II, single arm, open-label, multi-site trial studying the combination of cryoablation therapy and dual checkpoint inhibition with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) given at the recommended phase 2 dose (RP2D) in pediatric and young adult patients with relapsed or refractory solid tumors.
A Study of Surufatinib in Combination With Gemcitabine in Pediatric, Adolescent, and Young Adult...
Solid TumorLymphoma4 moreThe purpose of this study is to evaluate the safety and tolerability of surufatinib, thereby identifying the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of surufatinib administered in combination with gemcitabine in pediatric patients with recurrent or refractory solid tumors or lymphoma. The study will be conducted in 2 parts.
Cabozantinib S-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma
Metastatic Ewing SarcomaMetastatic Osteosarcoma8 moreThis phase II trial studies how well cabozantinib s-malate works in treating patients with osteosarcoma or Ewing sarcoma that has grown or returned (come back) after a period of improvement. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may also prevent the growth of new blood vessels that tumors need to grow.
iC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma and Neuroblastoma
OsteosarcomaNeuroblastomaThe purpose of this study is to find the largest safe dose of GD2-T cells (also called iC9-GD2-CAR-VZV-CTLs) in combination with a varicella zoster vaccine and lymohodepleting chemotherapy. Additionally, we will learn what the side effects of this treatment are and to see whether this therapy might help patients with advanced osteosarcoma and neuroblastoma. Because there is no standard treatment for recurrent/refractory osteosarcoma and neuroblastoma at this time or because the currently used treatments do not work fully in all cases, patients are being asked to volunteer to take part in a gene transfer research study using special immune cells. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that a new gene can be put into T cells that will make them recognize cancer cells and kill them. Investigators now want to see if a new gene can be put in these cells that will let the T cells recognize and kill sarcoma and neuroblastoma cells. The new gene is called a chimeric antigen receptor (CAR) and consists of an antibody called 14g2a that recognizes GD2, a protein that is found on sarcoma and neuroblastoma cells (GD2-CAR). In addition, it contains parts of the CD28 and OX40 genes which can stimulate T cells to make them live longer. Investigators have found that CAR-T cells can kill some of the tumor, but they don't last very long in the body and so the tumor eventually comes back. T cells that recognize the virus that causes chicken pox, varicella zoster virus (VZV), remain in the bloodstream for many years especially if they are stimulated or boosted by the VZV vaccine. Investigators will therefore insert the GD2-CAR gene into T cells that recognize VZV. These cells are called iC9-GD2-CAR-VZV-specific T cells but are referred to as GD2-T cells for simplicity.
Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors
GliomaNeuroectodermal Tumors7 moreThe purpose of this research study is to determine whether taking either of two low dose drugs that would prevent new blood vessels from growing after stem cell transplant is feasible, and what the side effects of taking each of these drugs after autologous transplant might be. The reason the investigators are looking at these drugs is because one of the things that allows tumors to grow quickly is their ability to stimulate the growth of new blood vessels. By suppressing the growth of new blood vessels after stem cell transplant, the investigators hope to prevent the tumors from coming back or continuing to grow.
Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin...
Advanced Malignant Solid NeoplasmAnn Arbor Stage III Hodgkin Lymphoma39 moreThis phase II Pediatric MATCH trial studies how well tazemetostat works in treating patients with brain tumors, solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have come back (relapsed) or do not respond to treatment (refractory) and have EZH2, SMARCB1, or SMARCA4 gene mutations. Tazemetostat may stop the growth of tumor cells by blocking EZH2 and its relation to some of the pathways needed for cell proliferation.
Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin...
Advanced Malignant Solid NeoplasmAnn Arbor Stage III Non-Hodgkin Lymphoma31 moreThis phase II Pediatric MATCH trial studies how well samotolisib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with TSC or PI3K/MTOR mutations that have spread to other places in the body (metastatic) and have come back (recurrent) or do not respond to treatment (refractory). Samotolisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin...
Advanced Malignant Solid NeoplasmRecurrent Childhood Ependymoma30 moreThis phase II Pediatric MATCH trial studies how well erdafitinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have spread to other places in the body and have come back or do not respond to treatment with FGFR mutations. Erdafitinib may stop the growth of cancer cells with FGFR mutations by blocking some of the enzymes needed for cell growth.
ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic...
OsteosarcomaThis is a phase II multicentre, uncontrolled trial including patients ≤ 40 years with non-metastatic extremity high-grade osteosarcoma stratified according to P-glicoprotein expression