May 20th, 2022 - Background: We generated an HLA-A*11:01-restricted murine T-cell receptor (mTCR) that specifically recognizes the G12V-mutated variant of KRAS (and other RAS family genes), expressed by many human cancers and constructed a single retroviral vector that contains its alpha and beta chains that confers recognition of this antigen when transduced into PBL. In co-cultures with HLA-A*11:01+ target ce...

May 20th, 2022 - Study Description: Individuals undergoing cisplatin-based chemoradiation therapy are at risk for developing significant, permanent hearing loss. The cholesterol-lowering drug atorvastatin has the potential to reduce the incidence and severity of hearing loss, as evidenced by our preclinical data in mice and our retrospective data in humans.Here we will compare hearing changes between subjects o...

May 20th, 2022 - Background: Adenosquamous carcinoma of the pancreas (ASCP) is a highly aggressive variant of pancreatic ductal adenocarcinoma (PDA), the most common type of pancreas cancer. ASCP is estimated to account for 0.5-4% of the 55,000 people who are diagnosed with pancreatic cancer in the U.S. each year, making it a very rare tumor type. No prospective clinical trials specific to ASCP have ever been p...

May 20th, 2022 - The purpose of this protocol is to obtain large numbers of CD34+ cells from the peripheral blood of healthy volunteers and patients with systemic mastocytosis or other related allergic, hematological, and immunological conditions by leukapheresis for culture and characterization of mast cell progenitor cells and their response to various cytokines and anti-mitotic agents. Healthy volunteers and...

May 20th, 2022 - Background: Over 80% of patients with advanced stage epithelial ovarian cancer will relapse Serum biomarkers are needed for predictors of persistent disease and relapse CA-125 is a less than satisfactory clinical tool for detecting relapse A serum repository of samples from women with ovarian cancer is needed to develop and validate the multiple tests being created for ovarian cancer recurrence...

May 20th, 2022 - Patients with malignant and non-malignant hematologic diseases including severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), acute and chronic leukemias, Hodgkin's and non-Hodgkin's lymphoma and multiple myeloma (MM) can now be cured by allogeneic bone marrow transplantation (BMT). This curative effect has been ascribed to the use of high dos...

May 20th, 2022 - Background: Olfactory neuroblastoma (ONB, also known as esthesioneuroblastoma), is a rare malignant neoplasm of the nasal cavity. At diagnosis, ONB is often locally advanced. It tends to invade locally and has high rates of regional spread to the neck, and distally to the lungs and bones. The 10-year survival rate for ONB is reported at 46%. Standard of care treatment is surgical resection foll...

May 20th, 2022 - Background: Pheochromocytomas/paragangliomas (PHEOs/PGLs) are rare tumors arising from neural crest tissue that can develop in sympathetic and parasympathetic paraganglia throughout the body. Those arising in the adrenal gland are called PHEOs while those located extraadrenally are called PGLs. While benign and uni-focal, PHEO/PGL can be effectively treated with surgical resection, participants...

May 20th, 2022 - This study consists of 3 phases: Screening Phase (up to 35 days), an Active Monitoring Phase or a Treatment Phase of 39 cycles or 36 months (whichever occurs first), and a Follow-up Phase which will continue until death, lost to follow-up, consent withdrawal, or study end (approximately 8 years after the first participant is randomized), whichever occurs first. Active monitoring cycles and trea...

May 20th, 2022 - Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second leading cause of cancer-associated mortality with an average life expectancy of 6-9 months Despite the success of several studies showing efficacy in treating HCC, most clinical trials have failed to prove a survival advantage. Adoptive T-cell therapy exploits the natural ability of T-cells to re...

May 20th, 2022 - Sirolimus (rapamycin), which acts as a targeted inhibitor of the protein mechanistic target of rapamycin (mTOR), has been shown to be effective in patients with lymphangioleiomyomatosis (LAM). It stabilizes lung function, resolves chylous effusions and lymphangioleiomas and shrinks angiomyolipomas. The current study is to understand better the short-term action of the drug by following the effe...

May 20th, 2022 - Background: Hairy cell leukemia (HCL) is highly responsive to but not curable by cladribine (CdA). HCL responds to rituximab, which is not yet standard therapy for HCL. Patients with the CD25-negative variant (HCLv) respond poorly to initial cladribine but do respond to rituximab in anecdotal reports. Purine analogs cladribine and pentostatin have similar efficacy for HCL, both inhibiting DNA s...

May 20th, 2022 - The study consists of 3 phases: Screening Phase (within 21 days prior to randomization), Treatment Phase (Cycle 1 Day 1 to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, withdrawal of consent, or the study ends, whichever occurs first). Treatment phase will include 2 treatments (Treatment A: participants ...

May 20th, 2022 - Background: Resections to remove tumors in the liver, bile ducts and pancreas are rarely curative, and patients frequently succumb to disease recurrence in the ensuing months to year(s) after the operation. Standard adjuvant therapies, which typically begin 6-12 weeks after surgery, offer little demonstrable decreases in the rates of tumor recurrence. The concept and implementation of immediate...

May 20th, 2022 - Background: Hairy cell leukemia (HCL) is an indolent CD22+ B-cell leukemia comprising 2% of all leukemias, or approximately 1200 of the 62,130 new cases of leukemia/year in the US. HCL variant (HCLv), also CD22+, is 10-20% as common as HCL, but more common in the relapsed/refractory population due to its poor prognosis and response to standard purine analog chemotherapy. HCLv cells are CD25-neg...

May 20th, 2022 - Individuals and families with known or suspected syndromes that include breast, ovarian or genetically-related cancers are enrolled in this family study, which is a syndrome-specific sub-set of the long-standing DCEG Human Genetics Program umbrella family studies protocol (78-C-0039). Cancer outcomes are documented through review of medical, vital, and pathology records. Selected individuals an...

May 20th, 2022 - Xeroderma Pigmentosum (XP) is a rare, recessive disorder with a more than 1000-fold increase in the frequency of all major skin cancers in association with defective DNA repair. The risk of skin and other cancers among normal appearing XP heterozygote individuals has not been fully studied. We plan to study the family members from XP families with known DNA repair gene mutations to determine if...

May 20th, 2022 - Background: Methylation-mediated silencing of genes is an epigenetic mechanism implicated in carcinogenesis; agents that inhibit this mechanism are of clinical interest because of their potential to re-activate silenced tumor suppressor genes. Two DNA hypomethylating nucleosides, 5-azacytidine (azacytidine) and 5-aza-2'-deoxycytidine (decitabine) have been approved by the FDA for the treatment ...

May 20th, 2022 - PAST PRE-CLINICAL AND CLINICAL EXPERIENCE: The effect of the electric fields (TTFields, TTF) has demonstrated significant activity in in vitro and in vivo pancreatic adenocarcinoma pre-clinical models both as a single modality treatment and in combination with chemotherapies. TTFields have been demonstrated to act synergistically with taxanes and have been shown to be additive when combined wit...

May 20th, 2022 - PRIMARY OBJECTIVES: I. To determine whether cabozantinib S-malate (cabozantinib) can significantly improve progression-free survival (PFS) compared to placebo in patients with advanced pancreatic neuroendocrine tumors (NET) whose disease has progressed after prior therapy. II. To determine whether cabozantinib can significantly improve progression-free survival (PFS) compared to placebo in pati...