Clinical Trials

That the comparative effectiveness of unsedated transnasal endoscopy (uTNE) will be greater than sedated endoscopy (sEGD) in population screening for BE.

Women with polycystic ovary syndrome (PCOS) have traditionally been treated for infertility by using progestin for a withdrawal bleed (aka endometrial shedding) before clomiphene citrate (CC) is administered to induce ovulation.

     Recent evidence suggests that this approach (the traditional CC protocol) may be associated with decreased pregnancy and live birth rates, compared to the "fast track" CC protocol (in which no progestin is used).

     The investigators are performing the first randomized controlled trial to find out if skipping the use of progestin (fast track CC protocol) during fertility therapy of anovulatory PCOS women leads to improved pregnancy and live birth rates compared to the traditional CC protocol.

OBJECTIVES:

     Primary

       -  To compare the complete remission rate in patients with high-risk follicular lymphoma receiving induction therapy comprising bendamustine hydrochloride and rituximab with vs without bortezomib.

       -  To compare the 1-year post-induction disease-free survival rate in patients receiving continuation therapy comprising rituximab with vs without lenalidomide.

     Secondary

       -  To determine the 3-year progression-free survival and the 5-year overall survival of these patients.

       -  To evaluate patient-reported outcomes at baseline and during treatment to determine differences in symptom palliation, treatment-related symptoms, and overall health-related quality of life.

       -  To examine the association between baseline FLIPI information and outcome of these patients.

       -  To examine the association between baseline and end-of-treatment patient comorbidities assessed by the Cumulative Illness Rating Scale (CIRS) and outcome.

       -  To create an image and tissue bank including serial PET/CT scans, diagnostic paraffin-embedded tissue, germline DNA, and serial blood and bone marrow samples sufficient to support proposed and future studies of tumor and host characteristics that may predict for clinical outcome, including treatment arm effects, and enhance existing prognostic indices. (exploratory)

     OUTLINE: Patients are stratified according to FLIPI-1score (1 or 2 vs 3 vs 4 or 5) and GELF tumor burden (low vs high). Patients are randomized to 1 of 3 treatment arms.

       -  Arm I: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

     Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

       -  Arm II: Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

     Beginning 4 weeks after the completion of induction therapy, patients receive rituximab as in arm I.

       -  Arm III: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

     Immediately after completing induction therapy, patients receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

     Quality of life (including fatigue, neurotoxicity, anxiety, and depression) is assessed by questionnaire at baseline and periodically during study therapy.

     Blood, bone marrow, and tissue samples may be collected periodically for correlative studies and for a repository.

     After completion of study therapy, patients are followed up periodically for 15 years.

OBJECTIVES:

       -  Determine the neuropsychological function in children with acute lymphoblastic leukemia treated with either high-dose methotrexate or escalating-dose methotrexate in the absence of cranial radiation and nelarabine.

       -  Identify host polymorphisms that predict an increased risk of neurocognitive dysfunction or acute neurotoxicity in these patients.

       -  Correlate neuropsychological outcome measures and the occurrence of acute neurotoxicity with host polymorphisms in these patients.

       -  Measure concentrations of 5-methyltetrahydrofolate, homocysteine, Ado, S-adenosylmethionine, S-adenosylhomocysteine, and other potentially relevant compounds in serum and cerebrospinal fluid during interim maintenance therapy with low- or high-dose methotrexate regimens, respectively, and correlate these endpoints with the occurrence of acute neurologic toxicity and long-term neurocognitive dysfunction in these patients.

       -  Determine whether or not diffusion tensor imaging will identify areas of selective vulnerability in CNS and provide an imaging modality that predicts and/or correlates with neuropsychological outcome.

     OUTLINE: This is a prospective, cohort, multicenter study.

     Patients complete neurocognitive tests to assess thinking, memory, attention, and concentration. The baseline test is administered during the consolidation phase of chemotherapy and further tests are done at 1 year from baseline and 1 year after* the completion of study therapy.

     Patients undergo blood and cerebrospinal fluid collection periodically for biomarker, genotypic polymorphisms, and pharmacokinetic analysis.

     Patients undergo MRI diffusion-tensor imaging to correlate imaging with neuropsychological outcomes.

     NOTE: * Within 8 months to 24 months after the completion of study therapy for patients on AALL0232.

     PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study.

OBJECTIVES:

     Primary

       -  To assess whether concurrent radiotherapy with daily temozolomide improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma.

       -  To assess whether adjuvant temozolomide improves survival as compared to no adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma.

     Secondary

       -  To assess whether concurrent and adjuvant temozolomide prolongs progression-free survival and neurological deterioration-free survival in patients with non-1p/19q deleted anaplastic glioma.

       -  To assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition.

       -  To assess the impact of concurrent and adjuvant temozolomide on the quality of life of patients with non-1p/19q deleted anaplastic glioma.

     OUTLINE: This is a multicenter study. Patients are stratified according to institution, WHO performance status (0 vs > 0), age (≤ 50 vs > 50), presence of 1p LOH only (yes vs no), presence of oligodendroglial elements (yes vs no), and O6-methylguanine-DNA methyltransferase promoter methylation status (methylated vs unmethylated vs indeterminate). Patients are randomized to 1 of 4 treatment arms.

       -  Arm I: Patients undergo radiotherapy* once daily, 5 days a week, for 6.5 weeks (total of 33 fractions).

       -  Arm II: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy).

       -  Arm III: Patients undergo radiotherapy* once daily, 5 days a week for 6.5 weeks (total of 33 fractions). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.

       -  Arm IV: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.

     NOTE: *Patients must begin radiotherapy within 8 days after randomization and within 7 weeks after surgery.

     In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

     Patients complete quality-of-life questionnaires, including QLQ-C30 version 3, BCM20, and the Mini Mental Status Exam at baseline, 4 weeks after the completion of radiotherapy, and then every 3 months for 5 years.

     Tissue samples are collected at baseline for histology review, 1p/19q analysis, methylation status of the O6-methylguanine-DNA methyltransferase promoter, and isocitrate dehydrogenase mutation analysis.

     After completion of study treatment, patients are followed every 3 months.

The Primary Hyperoxaluria Registry will help physicians, patients and their families better understand primary hyperoxaluria patients. The Registry is a web-based, confidential database. The information about your health will be maintained in the registry only by your assigned number and not by your name. The information will be maintained confidential in accordance with the local privacy regulations related to medical information. The information about your health will be maintained in the registry only by your assigned number and not by your name.

Because this disease is rare, most physicians typically have limited experience with primary hyperoxaluria patients. Therefore, the best ways to treat primary hyperoxaluria have not been well studied. Patients with primary hyperoxaluria have been diagnosed all over the world, however only a few patients are known in any individual country.

For these reasons, we are trying to combine all international research efforts and pool all information. A PRIMARY HYPEROXALURIA REGISTRY has been established by the Rare Kidney Stone Consortium and recently funded by the National Institutes of Health. Information collected in this registry will increase clinical and research-based understanding of the disease in a manner that no single center could do alone. By making this information available to the physicians and researchers who study primary hyperoxaluria, new ideas can be tested and research progress can be made faster. We are hoping that this may lead to earlier diagnosis and better treatments for you, your family members and other people living with primary hyperoxaluria.

Blood samples are obtained from those patients undergoing procedures to determine if a lung nodule is benign or cancerous. The data from the study will not be used to guide or influence the treatment of the patients enrolled in this study. There is no change from the normal standard of care that patients receive.

The study is being undertaken to understand how the Roux-en-Y Gastric Bypass procedure can affect insulin secretion after meals. The hypothesis of this study is the Disposition Index is decreased in subjects who had previously undergone Roux-en-Y Gastric Bypass by glucagon-like peptide-1 (GLP-1) receptor blockade.

The purpose of this study is to see if the investigators can identify early those patients who are admitted to the hospital and have a urinary tract infection (UTI) or those patients that develop a UTI during their hospitalization.

Different treatments exist for children with progressive or recurrent low-grade glioma. Each has variable efficacy at slowing or reversing growth, and exploration continues into finding better-tolerated, more effective treatments. Vinorelbine has recently generated interest in stabilizing some pediatric low-grade gliomas. It has been fairly well tolerated in both adult and pediatric studies that have examined its use in other tumors. In addition, the quality of life for children with low-grade gliomas is important and requires further study. This trial will incorporate an optional assessment using validated neuropsychological testing throughout treatment to evaluate the quality of life of the child being treated. Objective: To test the efficacy of Vinorelbine in a larger number of children with pediatric low-grade glioma that has returned or continues to grow. In this trial, Vinorelbine will be given intravenously once a week for 6 weeks followed by a 2 week rest. This cycle can then be repeated for up to 1-2 years if providing clinical benefit.