A RANDOMIZED PHASE 3 TRIAL OF CONTINUOUS VS. INTERMITTENT MAINTENANCE THERAPY WITH ZANUBRUTINIB AS UPFRONT TREATMENT IN OLDER PATIENTS WITH MANTLE CELL LYMPHOMA (INTERCON)
This is a Phase 3 study testing whether continuous or intermittent treatment with the study medicine Zanubrutinib (a kinase inhibitor) and rituximab (a monoclonal antibody) is a more effective treatment option for older patients with Mantle cell lymphoma. Once the patient is enrolled in the study, they will receive the study medicine Zanubrutinib and rituximab. Patients from this group whose cancer does not grow or spread will be randomly divided into two groups. Group A patients will continue the study medicine until their cancer comes back, or they have bad side effects from the study medicine. Group B patients will continue the study medicine until their cancer comes back (progression). Patients will restart the study medicine Zanubrutinib within less than 21 days after the confirmed progression of their cancer. Patients will continue to receive the study treatment until their cancer comes back for the second time (second progression) or unacceptable side effects. Special scans will be performed on all patients during the study to see whether the tumor size is changing. All patients will be closely monitored for side effects and safety concerns and will be followed up every 6 months for 10 years following registration.
An Open-label Randomized Phase 3 Study of MK-2870 as a Single Agent and in Combination with Pembrolizumab Versus Treatment of Physician s Choice in Participants with HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer
This clinical study will evaluate MK-2870 either alone or in combination with pembrolizumab versus TPC in participants with HR+/HER2- (both HER2-zero and HER2-low) unresectable locally advanced or MBC, who have not been previously treatedwith chemotherapy in the metastatic setting.
Cellular Viscosity as a Marker for Alzheimer s Disease Pathology: A Combined Multiparametric MR Spectroscopy and PET Study
This project proposes the use of Magnetic Resonance Spectroscopic Fingerprinting (MRSF) to quantify changes in intracellular viscosity separately within neurons and astrocytes and assess AD pathophysiology. We will work with the NYU AD Research Center to include our MRSF sequence within their routine tau-PET/MRI protocol, allowing for serial follow-up of a cohort of 100 cognitively normal individuals and patients with mild cognitive impairment. Both sets of subjects will undergo yearly neurocognitive assessments, plasma Aß and plasma tau evaluations; and biennial Aß-PET, tau-PET, and MRI+MRSF scans. The expected outcome of this work is a set of novel markers for neuronal and astrocytic intracellular viscosity which will potentially become biomarkers for early prediction of neurodegeneration and cognitive decline in AD, addressing gaps in the current imaging armamentarium of the AT(N) network.
Electronic cigarettes as a harm reduction strategy in people living with HIV/AIDS
People living with HIV/AIDS (PLWHA) are known to have exceptionally higher rate of cigarette smoking and very low quit rates compared to the general population. Although a primary rationale for conducting this study is reducing health disparities among PLWHA, there is a potential benefit of the proposed work from a prevention perspective given that combustible cigarette smoking is an independent risk factor for non-adherence to ART and may decrease the effectiveness of HAART (1-5). Smoking-related illnesses are leading causes of non-HIV/AIDS-related deaths among People Living with HIV/AIDS (PLWHA). (6) There are major yet unique barriers to combustible cigarette (CC) cessation among PLWHA.7? Additionally, FDA approved CC cessation medications have not been effective with this population. (8-11) Electronic cigarettes (E-cigarettes) could help people reduce the harm of CC through reductions in number of Cigarettes per Day (CPD) or quitting CC completely by addressing both nicotine and behavioral dependence. (12-14) A harm reduction approach may be more appropriate to use with PLWHA.15 This mixed-methods study’s purpose is to identify barriers and facilitators, as well as assess preliminary effectiveness of e-cigarettes as a harm reduction strategy among PLWHA.
First-in-Human Study of Mutant-Selective PI3Ka Inhibitor RLY- 2608 as a Single Agent in Advanced Solid Tumor Patients and in Combination with Fulvestrant in Patients with Advanced Breast Cancer
GOG-3082 - Phase 1b/2 Basket Study of ACR-368 as Monotherapy and in Combination with Gemcitabine in Adult Subjects with Platinum-Resistant Ovarian Carcinoma Endometrial Adenocarcinoma and Urothelial Carcinoma Based on Acrivon OncoSignature Status
This is a clinical study to test a drug called ACR-368 (also known as Prexasertib) for the treatment of ovarian, endometrial, and urothelial cancer that has returned and is resistant to platinum-based chemotherapy. The study will test ACR-368 on its own and in combination with a low-dose chemotherapy drug called Gemcitabine. Patients will be selected for the study based on the results of a test called OncoSignature (a patient selection tumor biopsy test), which will predict how effective ACR-368 will be for each patient. Patients will be allocated to one of two groups based on their OncoSignature result: Arm 1 for patients with a positive OncoSignature result and Arm 2 for patients with a negative or inconclusive OncoSignature result. In Arm 1, patients with a positive OncoSignature result will receive ACR-368 alone in a Phase 2 study. In Arm 2, patients with a negative or inconclusive OncoSignature result will receive a combination of ACR-368 and low-dose gemcitabine in a Phase 1b study to determine the safe and recommended dose of the combination. A Phase 2 study will then test the combination for effectiveness and safety in each cancer type.
Gut microbiome alterations as a mechanism of immune dysregulation in new-onset refractory status epilepticus (NORSE)
We will perform a prospective, observational cohort study, with biospecimen collection, of NORSE subjects and subjects with status epilepticus of known cause (e.g. epilepsy, stroke, traumatic brain injury) serving as disease controls. Biospecimens to be collected include serum, CSF, and feces, which will all be analyzed in conjunction with relevant clinical outcome measures collected via prospective chart reviews of these subjects' hospital stays. These analyses will allow us to test our hypothesis that in subjects with status epilepticus, gut dysbiosis leads to IL-1b upregulation, which enhances neuronal hyperexcitability and contributes to refractory status epilepticus.
MICROBiome Involvement in Outcomes of Methotrexate Efficacy-RA
This is a prospective, observational, proof-of-principle, open-label, single-blinded study looking at the effects of the gut microbiome on the metabolism and response to methotrexate treatment and related medications. MTX will be taken at standard-of-care doses in drug-naïve RA patients who have active disease and have not received other disease-modifying therapies (as defined by the inclusion/exclusion criteria).
Phase 1 study of intratumoral administration of JNJ-87704916 an oncolytic virus as monotherapy and in combination for advanced solid tumors
This is a phase 1 study, testing the study medicine JNJ-87704916 (an oncolytic herpes simplex virus type 1, HSV-1) alone or in combination with another medicine, cetrelimab (a PD-1 antibody), in patients with advanced solid tumors. This study has two parts. In part 1 of the study, the study team will gradually increase the dose of the study medicine to find out the most effective dose that works well with fewer side effects. In part two, the patients will be divided into two groups. Group A will include patients whose lung cancer has spread from the primary location and the tumor has no PDL-1 expression (PD-L1
Phase 3 Randomized Open-label Multicenter Study to Compare the Efficacy and Safety of Sacituzumab Tirumotecan in Combination with Pembrolizumab Versus Pembrolizumab Alone as First-line Maintenance Treatment in Participants with Mismatch Repair Proficient Endometrial Cancer (TroFuse-033/GOG-3119/ENGOT-en29)
This is a Phase 3 trial testing whether the study medicine sacituzumab tirumotecan (an antibody-drug conjugate, also known as sac-TMT, or MK-2870), when given in combination with another medicine called pembrolizumab (an immunotherapy medicine), is effective and a better treatment in patients with a specific type of endometrial cancer called proficient (pMMR) endometrial cancer. This trial will compare treatment with sac-TMT plus pembrolizumab to pembrolizumab alone. This study has two parts- Part 1 is the Induction phase, where patients will receive pembrolizumab and chemotherapy, and Part 2 is the Maintenance phase, where patients whose cancer has not progressed, as shown by the CT scans, will be divided into two groups to receive either sac-TMT plus pembrolizumab or pembrolizumab alone. Patients will undergo CT scans during the study to see how their cancer is changing in response to the study treatment. Blood samples will be taken from all patients to see how their bodies are handling the study medicine. All patients will be closely monitored for any side effects and safety concerns.