Paterson

Researchers are investigating the best way to combine chemotherapy and radiation therapy for patients aged 3 to 29 years with localized non-germinomatous germ cell tumors NGGCT in the brain. This phase II trial aims to optimize treatment based on how well the tumor responds to initial chemotherapy, with the goal of reducing spinal cord relapses and adjusting therapy for better disease control. The study also compares different radiation types and examines cognitive and physical effects in children and young adults with NGGCT. Participants first receive induction chemotherapy consisting of carboplatin, etoposide, and ifosfamide over six cycles every 21 days. Based on tumor response, patients are assigned to one of two plans Plan A involves whole ventricular plus spinal canal irradiation WVSCI, delivered daily for 6 weeks, while Plan B includes high-dose chemotherapy with stem cell transplant followed by radiation therapy to the whole brain and spine. Some patients may undergo second-look surgery depending on tumor response before continuing treatment. Throughout the study, participants undergo MRI scans, collection of cerebrospinal fluid and blood samples, and questionnaires assessing cognitive, social, and behavioral functioning. Researchers monitor tumor response, progression-free survival, overall survival, and patterns of disease recurrence for up to 10 years. Safety and side effects are also evaluated to better understand long-term outcomes of these treatment approaches.

Researchers are evaluating how well combination chemotherapy works in treating patients with newly diagnosed stages 2 to 4 diffuse anaplastic Wilms tumor DAWT and patients with relapsed favorable histology Wilms tumor FHWT. This phase II trial compares the effects of two chemotherapy regimens, UH-3 and ICECycloTopo, on event-free survival and overall survival, aiming to improve outcomes based on different relapse risk groups and prior treatments. The study also explores kidney toxicity, genetic markers, surgery impacts, and radiation therapy techniques to reduce side effects and better understand tumor behavior. Participants are assigned to one of two treatment groups. In Arm I Regimen UH-3, patients receive cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan intravenously over various days in a 21-day cycle, with radiation therapy at week 7 of cycle 3 if needed. In Arm II Regimen ICECycloTopo, patients receive cycles of carboplatin, etoposide, ifosfamide, cyclophosphamide, and topotecan intravenously over 10 cycles every 21 days, with surgery andor radiation therapy during certain cycles as clinically indicated. Throughout the trial, patients undergo multiple imaging tests including CT scans, PET scans, chest x-rays, MRIs, abdominal ultrasounds, and bone scans, along with blood sample collections and biopsies. After completing treatment, follow-up visits occur every 3 months for the first 2 years, then every 6 months for years 3 and 4, and once at year 5. The main outcomes measured are event-free survival and overall survival up to 5 years from study entry, with ongoing monitoring for treatment effects and safety.

Researchers are evaluating a phase II trial studying how well lower dose radiotherapy after chemotherapy works in treating children and young adults with central nervous system CNS germinomas. This trial aims to compare reduced radiation doses to standard treatment while maintaining effectiveness, potentially reducing long-term side effects. The study also investigates survival rates, tumor response, neuroendocrine function, and cognitive processing speed in participants with localized, metastatic, and basal ganglia or thalamic germinomas. Participants receive chemotherapy with carboplatin and etoposide intravenously over several days, repeated every 21 days for up to four cycles. After chemotherapy, patients are assigned to different treatment groups strata based on tumor response and location. Radiation therapy is delivered using advanced techniques such as 3D conformal radiation, proton therapy, or intensity-modulated radiation daily on weekdays for 16 to 24 days depending on the stratum. Some patients may undergo second-look surgery. The study includes collection of blood, cerebrospinal fluid, and tumor tissue samples for research. Throughout the study, participants undergo MRI scans and may have lumbar punctures for cerebrospinal fluid collection. Follow-up occurs every three months for the first year, then every four months for two years, and annually up to ten years. Researchers measure event-free survival, overall survival, tumor response, neuroendocrine function, and cognitive processing speed at multiple time points. The study also monitors for cerebral vascular events and evaluates long-term cognitive, social, and behavioral outcomes.

Researchers are studying children and young adults with newly diagnosed diffuse intrinsic pontine glioma DIPG or high-grade glioma HGG that have a specific genetic change called H3 K27M mutation. This phase III trial evaluates the safety, side effects, and best dose of the drug selinexor combined with standard radiation therapy, and aims to determine how well this combination shrinks tumors in these patients. DIPG is a high-risk brain tumor located in a critical area of the brainstem, and HGG refers to rapidly growing glioma tumors in the brain or spine. Participants receive standard radiation therapy five days a week for 5 to 7 weeks. Beginning on day 4 or 5 of radiation, selinexor is given orally on specific days during this period. After a two-week rest, patients enter a maintenance phase where selinexor is taken orally on days 1, 8, 15, and 22 of each 28-day cycle, for up to 24 cycles if there is no disease progression or unacceptable side effects. Magnetic resonance imaging MRI scans and possibly a biopsy are done before treatment and during follow-up. During the study, participants are monitored closely with MRIs and clinical evaluations to assess side effects and tumor response. Researchers measure the maximum tolerated dose of selinexor, event-free survival, overall survival, and response rates over up to five years. After treatment, patients are followed every three months during the first year, then every six months for two years, and annually for years four and five to track long-term outcomes and safety.

Researchers are evaluating treatments for children and young adults with low-risk and average-risk medulloblastoma, a type of brain cancer. This phase III trial aims to reduce hearing loss caused by cisplatin chemotherapy in average-risk patients by adding sodium thiosulfate STS to standard treatment. For low-risk patients, the study tests whether reduced radiation therapy can maintain benefits while causing fewer side effects. The study also monitors survival, tumor recurrence, and quality of life outcomes. Participants receive radiation therapy five days a week for six weeks, alongside weekly vincristine infusions during this period. Following chemoradiotherapy, maintenance therapy includes cycles of lomustine, cisplatin, sodium thiosulfate, cyclophosphamide, and vincristine given on specific days over up to nine cycles, depending on tolerance and disease progression. Patients undergo regular MRI scans and may provide cerebrospinal fluid and blood samples during the study. Throughout the trial, participants are closely monitored with hearing tests, neurocognitive assessments, and quality-of-life surveys. Follow-up visits occur every three months for the first two years, every six months for years three and four, and annually up to ten years to track hearing loss, event-free survival, overall survival, tumor recurrence, and psychosocial outcomes. The study also collects biological samples for future molecular research, with the total participation lasting up to ten years.

This trial studies children, adolescents, and young adults with Philadelphia chromosome positive Ph or ABL-class Philadelphia chromosome-like Ph-like B-cell acute lymphoblastic leukemia B-ALL. It evaluates the combination of blinatumomab with dasatinib or imatinib alongside standard chemotherapy. The study aims to estimate 3-year event-free survival and overall survival, describe safety and toxicity, and explore treatment responses and immune function in these patients. Participants receive a modified chemotherapy regimen including multiple cycles of blinatumomab without traditional consolidation chemotherapy combined with continuous tyrosine kinase inhibitors dasatinib or imatinib depending on fusion subtype. Treatment includes induction phases, blinatumomab blocks, interim maintenance, delayed intensification, and maintenance cycles over two years, with various drugs administered orally, intravenously, or intrathecally. Radiation therapy may be given in some cases. Throughout the study, participants undergo blood and cerebrospinal fluid sample collection, bone marrow biopsies, and heart function tests such as echocardiography or multigated acquisition scans. Researchers monitor minimal residual disease, treatment-related side effects, and long-term outcomes up to three years. The study involves regular assessments to evaluate treatment effectiveness and safety over the full duration of therapy.

Researchers are evaluating the combination of nivolumab and blinatumomab compared to blinatumomab alone in children and young adults aged 1 to under 31 years with first relapse of CD19 B-cell acute lymphoblastic leukemia B-ALL, including patients with Down syndrome. This phase II trial aims to compare event-free survival after reinduction and consolidation therapy, assess safety and tolerability, and explore various outcomes such as remission rates and toxicity, with follow-up up to 10 years after enrollment. Participants receive treatments based on their assigned groups and arms, involving cycles of immunotherapy including blinatumomab, nivolumab, dexamethasone, methotrexate, and other chemotherapy drugs given by various routes such as intravenous infusion, intrathecal injection, and oral administration. Treatment cycles repeat every 36 or 37 days for up to two cycles, with some groups receiving radiation therapy or maintenance chemotherapy afterward. Patients with high white blood cell counts or specific disease locations may receive pre-immunotherapy treatments. Throughout the study, participants undergo lumbar punctures, bone marrow biopsies and aspirations, and collection of blood, urine, and cerebrospinal fluid for monitoring. Researchers measure outcomes such as minimal residual disease negative remission rates and event-free survival. After completing treatment, participants are followed every three months for one year to monitor their health and any long-term treatment effects.

Researchers are evaluating a new treatment approach for children and young adults newly diagnosed with acute myeloid leukemia AML, including those with and without FLT3 gene mutations. The trial compares standard chemotherapy using daunorubicin, cytarabine, and gemtuzumab ozogamicin to therapy with CPX-351, a liposome-encapsulated form of daunorubicin and cytarabine, andor the drug gilteritinib which may block abnormal FLT3 gene function. The study aims to understand which treatment works better and to monitor heart function changes during and after therapy. Participants are assigned to different treatment groups based on their risk and FLT3 mutation status. Treatments include various chemotherapy regimens delivered intravenously and intrathecally, with some groups receiving CPX-351 and others receiving standard drugs. Patients with FLT3 mutations receive additional oral gilteritinib for extended periods, including maintenance therapy up to one year. Hematopoietic stem cell transplantation is also part of the treatment for some high-risk patients following chemotherapy courses. During the study, participants will undergo multiple assessments including blood tests, bone marrow biopsies, imaging scans, and neuropsychological testing to monitor leukemia status and treatment effects. Cardiac function is closely followed using echocardiography and biomarkers. Patient outcomes such as event-free survival, overall survival, minimal residual disease, relapse rates, and treatment safety are tracked for up to three years. The total study participation may extend over several years with ongoing evaluations.

Researchers are evaluating whether adding immunotherapy drugs brentuximab vedotin and nivolumab to the standard treatment of chemotherapy with or without radiation improves survival for patients aged 5 to 60 with early stage classical Hodgkin lymphoma. This phase III trial compares progression-free survival and overall survival between the standard therapy and the immunotherapy-enhanced approach, as well as patient-reported outcomes and long-term side effects. Participants initially receive two cycles of ABVD chemotherapy every 28 days and then undergo imaging to classify their early response. Based on risk level and response, patients are assigned to one of eight treatment arms that include either continuing standard chemotherapy, receiving immunotherapy drugs, or combinations with involved-site radiation therapy. Treatments are delivered intravenously or orally in cycles lasting 28 days. Imaging and blood samples are collected throughout the trial. Participants are monitored regularly with PET scans, CT or MRI imaging, and blood tests. Follow-up visits occur every 3 months in the first year, then every 6 months for years two and three, and annually up to 12 years from registration. Researchers assess survival outcomes, adverse events, patient-reported symptoms and quality of life, and metabolic tumor burden. Long-term effects such as cardiovascular and pulmonary health are also evaluated using questionnaires and clinical assessments.

Researchers are comparing the effectiveness of two different combinations of immunotherapy drugs with chemotherapy for adults with stage IV or recurrent non-squamous non-small cell lung cancer that has PD-L1 expression of 1% or higher. This phase 3, randomized study focuses on participants who have not previously received systemic treatment for advanced disease. The goal is to determine which combination better improves overall survival and other outcomes in this patient group. Participants will be randomly assigned to receive either Nivolumab plus Relatlimab combined with chemotherapy or Pembrolizumab combined with chemotherapy. The chemotherapy drugs used include Carboplatin, Pemetrexed, or Cisplatin, given in specified doses on scheduled days. Treatment is given as first-line therapy for their cancer, with dosing details managed throughout the study period. During the study, participants will undergo imaging scans like CT or MRI to measure disease status, and blood tests to monitor safety and side effects. The main outcome measured is overall survival over up to five years, along with progression-free survival, response rates, duration of response, and adverse events. Researchers will also assess symptoms related to lung cancer over two years. Participants are monitored regularly to track these outcomes and ensure safety throughout the study duration, which may last several years.