Brief Summary
This single arm study is designed to demonstrate the feasibility of a radically different approach for an exceptionally high-risk subset of MES with widely metastatic disease (WMES). We incorporate the use of evolutionary principles that apply to species and population dynamics as related to adaptation and extinction to populations of cancer cells that similarly adapt and that we are attempting to make extinct, resulting in a cure for the patient. Such principles include an initial intense first strike to deplete the bulk of the cancer cells, followed by a series of sequential second strikes towards eliminating residual, resistant populations, followed by a prolonged period of maintenance chemotherapy to eliminate any remnant cells, using agents generally regarded to be active against newly diagnosed ES.
Protocol Interventions
Drug: Vincristine, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: Ifosfamide, Drug: Actinomycin, Drug: Irinotecan, Drug: Cabozantinib, Drug: Topotecan, Drug: Temozolomide, Drug: Etoposide, Drug: Liposomal doxorubicin
Brief Summary
This randomized, open-label, parallel group, two-arm, multi-center assessment will compare IV BCV with IV CDV in adult and pediatric allogeneic HCT recipients with AdV viremia. A virologic response-driven approach to duration of treatment will be evaluated, in which randomized subjects are treated with either BCV or CDV until AdV viremia is confirmed as undetectable or until a maximum of 12 weeks of therapy, whichever occurs first. All subjects will be followed for a total of 24 weeks post-randomization, regardless of treatment assignment. Subjects will be assessed on a weekly basis through the end of treatment visit (EOT). Additional assessments will be performed at the test of cure (TOC) visit, which is 4 weeks after the last dose of study drug and at Weeks 12 and 24 post W1D1.
Protocol Interventions
Drug: cidofovir
Brief Summary
This study is designed to demonstrate the efficacy and assess safety and tolerability of oral daily alpelisib in participants with PIK3CA-related overgrowth spectrum (PROS).
Protocol Interventions
Drug: Alpelisib
Brief Summary
This phase II trial studies how well de-escalating the drugs dabrafenib and trametinib works in treating patients with low-grade gliomas that have a BRAF V600 gene mutation. Dabrafenib and trametinib are in a class of medications called kinase inhibitors. They work by blocking the action of abnormal proteins that signals tumor cells to multiply. This helps stop the spread of tumor cells. This trial may help doctors determine the best dosing strategy for patients who have received dabrafenib and trametinib for 12-24 months: Either stopping dabrafenib and trametinib completely or slowly reducing the dose for an additional 6 months.
Protocol Interventions
Drug: Dabrafenib, Drug: Trametinib, Procedure: Magnetic Resonance Imaging (MRI), Procedure: Specimen Collection, Procedure: Optional Lumbar puncture
Brief Summary
Safety, tolerability and efficacy of Descarte-08 in children, adolescents and young adults with childhood-onset systemic lupus erythematosus, ANCA-associated vasculitis, juvenile myasthenia gravis, and juvenile dermatomyositis
Protocol Interventions
Drug: Descartes-08
Brief Summary
This pilot trial assesses the effect of the combination of blinatumomab with dasatinib or imatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (Ph+) or ABL-class Philadelphia chromosome-like (Ph-like) B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system’s fighting response) at the same time. Blinatumomab may strengthen the immune system’s ability to fight cancer cells by activating the body’s own immune cells to destroy the tumor. Dasatinib and imatinib are in a class of medications called tyrosine kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib or imatinib in combination with standard chemotherapy may work better in treating patients with Ph+ or Ph-like ABL-class B-ALL than dasatinib or imatinib with chemotherapy.
Protocol Interventions
Procedure: Biospecimen Collection, Biological: Blinatumomab, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dasatinib, Drug: Daunorubicin, Drug: Doxorubicin, Procedure: Echocardiography Test, Drug: Leucovorin, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Drug: Pegaspargase, Drug: Prednisolone, Drug: Prednisone, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine
Brief Summary
This is an open-label, comprehensive, iterative investigation of evaluating the use of induction chemotherapy, high-dose chemotherapy, and focal radiation therapy in children with newly diagnosed Embryonal Tumor With Multilayered Rosettes (ETMR).
Protocol Interventions
Radiation: Radiotherapy (RT), Drug: Chemotherapy Drug, Cancer – Physician’s Choice, Procedure: Non-Investigational Surgical Resection, Drug: Temozolomide, Procedure: Tumor Tissue Sample, Procedure: Blood Sample, Procedure: Cerebrospinal Fluid (CSF) Sample
Brief Summary
This phase I/II trial tests the safety, side effects and best dose of DT2216 in combination with irinotecan and how well it works in treating children, adolescents and young adults with solid tumors and fibrolamellar cancer that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). DT2216 is an anti-apoptotic protein B-cell lymphoma-extra large targeted protein degrader. It may stop the growth of tumor cells by blocking Bcl-xL, a protein needed for tumor cell survival. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid repair and may kill tumor cells. Giving DT2216 in combination with irinotecan may be safe, tolerable, and/or effective in treating children, adolescents and young adults with relapsed or refractory solid tumors or fibrolamellar cancer.
Protocol Interventions
Biological: Bcl-XL Proteolysis Targeting Chimera DT2216, Procedure: Biospecimen Collection, Drug: Irinotecan
Brief Summary
This phase I clinical trial studies the side effects and best dose of AZD1390 and to see how well it works when given together with radiation therapy for the treatment of pediatric patients with high grade glioma, diffuse midline glioma or diffuse intrinsic pontine glioma. AZD1390 is in a class of medications called kinase inhibitors. It works by blocking the signals that cause cancer cells to repair deoxyribonucleic acid damage caused by cancer treatments, such as radiation therapy. This may help overcome resistance to therapy seen in these cancers and therefore lead to increased death of cancer cells. Radiation therapy uses high energy x-rays or particles to kill cancer cells and shrink tumors. Giving AZD1390 with radiation may be safe, tolerable, and effective in treating pediatric patients with high grade glioma, diffuse midline glioma or diffuse intrinsic pontine glioma.
Protocol Interventions
Drug: ATM Kinase Inhibitor AZD1390, Procedure: Biospecimen Collection, Procedure: Magnetic Resonance Imaging, Radiation: Radiation Therapy, Other: Survey Administration
Brief Summary
This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy 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. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.
Protocol Interventions
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Computed Tomography, Procedure: Echocardiography Test, Procedure: FDG-Positron Emission Tomography, Procedure: Lumbar Puncture, Procedure: Magnetic Resonance Imaging, Drug: Methylprednisolone, Procedure: Multigated Acquisition Scan, Drug: Prednisolone, Drug: Prednisone
