Clinical Trials

This study is being conducted to assess varenicline and bupropion as aids to smoking cessation treatment in subjects with and without an established diagnosis of major psychiatric disorder and to characterize the neuropsychiatric safety profile (pre-specified adverse events (AEs) in both of these populations).

The purpose of this study is to determine whether the endotracheal cardiac output monitor (ECOM) is accurate and predictive in liver failure patients with hyperdynamic circulatory changes.

Hepatorenal syndrome is a rare syndrome of marked renal dysfunction in patients with cirrhosis, decompensated liver disease, and portal hypertension. Hepatorenal syndrome type 1 is characterized by a rapid progressive renal impairment and has a very poor prognosis with > 80% mortality within 3 months. At present, there are no approved drug therapies for HRS type 1 in the US, Australia, or Canada. The only curative treatment for HRS type 1 and the underlying end-stage cirrhosis is liver transplantation. However, many patients will not survive long enough to receive a liver transplant and therapy, which may provide a bridge to transplantation, is badly needed. Increased understanding of the pathophysiology of HRS type 1 has demonstrated that vasoconstrictive drug therapy may reverse HRS type 1. Substantial data available from many published clinical investigations in the literature provide compelling evidence suggesting that administration of terlipressin improves renal function in patients with HRS.

OBJECTIVES: Primary - To collect clinical data and family histories and blood and/or tissue samples from patients diagnosed with pancreatic diseases, including pancreatic cancer, for use in future studies. - To collect information regarding food preparation and intake in these patients. Secondary - To make available to researchers medical data and biospecimens to enable them to develop better ways to screen people at risk for pancreatic conditions, including pancreatic cancer. - To investigate genes or substances that increase susceptibility of developing pancreatic conditions. - To find agents that may help prevent, treat, or cure these conditions. - To learn whether inherited factors increase the risk of pancreatic diseases, pancreatic cancer, or other cancers. OUTLINE: This is a multicenter study. Patients complete two 1-hour surveys assessing health, clinical and family history of pancreatic conditions including cancer, and food preparation and intake. Patients also complete a 15- to 30-minute follow up survey at 6 months and 1 year to assess health, health practices, and family history. A review of the patient's medical information is obtained from the medical record. Blood samples are collected for future research studies. Oral cells and stool samples may also be collected for future studies.

THE STUDY WILL ANSWER WHETHER INHALED BUDESONIDE AND FORMOTEROL ARE ABLE TO ALLEVIATE OR PREVENT PULMONARY INJURY WHEN ADMINISTERED EARLY IN HOSPITAL COURSE TO THE PATIENTS AT RISK FOR DEVELOPING ARDS

Bone marrow aspirate is collected and processed by centrifugation to remove red blood cells. The resulting concentrate of cells is injected into ischemic tissues of the lower limb. The purpose of this study is to determine if injections of concentrated bone marrow nucleated cells into ischemic tissues will result in vasculogenesis.

PRIMARY OBJECTIVES: I. To determine the maximally tolerated doses of dinaciclib and bortezomib, when used in combination, in two different schedules, for treatment of relapsed multiple myeloma. SECONDARY OBJECTIVES: I. To determine the toxicities associated with dinaciclib and bortezomib, when used in combination, for treatment of relapsed multiple myeloma. II. To determine the overall response rate associated with dinaciclib and bortezomib, when used in combination, for treatment of relapsed multiple myeloma. III. To explore the differences in toxicity associated with two different schedules of dinaciclib and bortezomib used in combination. TERTIARY OBJECTIVES: I. To examine if expression levels of target cyclin dependent kinase (CDK): CDK 2,5,7 and 9 levels in cluster of differentiation (CD)138-purified tumor cells, will be correlated with response (clinical and molecular) to determine if high or low level target CDK expression, if present, influences dinaciclib efficacy. II. To examine if immunoglobulin (Ig)H translocation status, P53 status and presence of Myc amplification or rearrangement, determined on patient bone marrow before treatment, using a pre validated fluorescence in situ hybridization (FISH) panel to identify common myeloma translocations, will be correlated with molecular and/or clinical markers of drug activity, and to assess if specific genetic subgroups of myeloma tumors are responsive or resistant. III. To determine the gene expression profiles of myeloma cells before and after treatment to understand the role of tumor gene dysregulation and/or dinaciclib induced effects on transcription. OUTLINE: This is a dose escalation study of dinaciclib and bortezomib. Patients are assigned to 1 of 2 treatment schedules. SCHEDULE I: Patients receive dinaciclib intravenously (IV) over 2 hours and bortezomib subcutaneously (SC) on days 1, 8, and 15 and dexamethasone orally (PO) once daily (QD) on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. SCHEDULE II: Patients receive dinaciclib IV over 2 hours on day 1; bortezomib SC on days 1 and 8; and dexamethasone PO QD on days 1, 2, 8, and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 and 90 days.

Fatigue is the most common symptom of multiple sclerosis (MS), affecting up to 90% of people with the disease. MS-related fatigue can be disabling even when other features of MS are mild. It can interfere with physical activity, memory and thinking, social and family activities, and ability to work. Initial treatment consists of energy conservation techniques such as rest periods or naps but when these approaches fail doctors usually recommend a trial of medications. Amantadine, modafinil, and other stimulants are commonly used but help only about half of those who try them. It is unlikely that these drugs directly affect the cause of MS-related fatigue. It has been difficult to develop new drug therapies for MS-related fatigue because we do not fully understand its causes and do not have precise ways to measure it. We rely on a person?s self-report about their fatigue but individuals experience and report fatigue differently. Recent research has shown that some fatigue aspects, such as difficulty maintaining mental concentration (?cognitive fatigue?) and physical activity (?motor fatigue?), can be measured more precisely and require further study. We recently reported results from a study showing that people taking the equivalent of four regular aspirin tablets (1300 mg) daily had reduced MS-related fatigue compared with placebo (sugar pill). The current proposal will attempt to confirm the benefit of aspirin in a larger group of people and to determine if the benefit is related to inflammation. One hundred and thirty-five people with MS-related fatigue will participate at MS clinics at three Mayo Clinic sites. Participants will complete questionnaires that ask about the severity and impact of their fatigue, memory testing to assess cognitive fatigue, and have blood testing to measure markers of inflammation. At the Arizona site, participants will also do strength testing in a motor laboratory to assess motor fatigue. After obtaining two separate baseline evaluations, the participants will be randomly assigned treatment such that one-third will receive 1300 mg per day of aspirin, one-third will receive 162 mg per day of aspirin and one-third will receive a matching placebo. All participants will then return to the clinic on two more occasions over the next eight weeks to repeat the questionnaires, memory and strength testing, blood tests, and report any side-effects. At the end of the study, the results of one of the fatigue questionnaires will be analyzed to determine if aspirin significantly improved fatigue compared with the placebo. The results of other questionnaires and the memory and strength testing will be analyzed as supportive evidence. If this study is successful, it will provide strong scientific evidence that aspirin helps MS-related fatigue. It will add an important new option for treatment of all MS patients that is also familiar, inexpensive, and has a good long-term safety record. At the same time, it will allow us to better understand the causes of MS-related fatigue and how to measure it more precisely. This information will be extremely useful for development of other therapies in the future.

PRIMARY OBJECTIVES: I. To assess the anti-tumor activity (in terms of the tumor response rate using the Response Evaluation Criteria in Solid Tumors [RECIST] criteria) of pazopanib (pazopanib hydrochloride) (GW786034) in patients with advanced malignant pheochromocytomas and paragangliomas. SECONDARY OBJEC TIVES: I. To assess safety profile of pazopanib. II. To assess duration of tumor response. III. To assess time to treatment failure. IV. To assess progression-free survival time. V. To assess overall survival time. TERTIARY OBJECTIVES: I. For patients with secretory tumors, to examine changes in urinary catecholamine and/or metanephrine levels. II. For patients with secretory tumors, to examine whether pazopanib-induced changes in urinary catecholamine and/or metanephrine levels during the first cycle of treatment may be associated with objective tumor response. III. To examine associations between tumor response and somatic mutational status in archived tumors, or germline mutational status in patient's peripheral blood mononuclear cells, (presence of succinate dehydrogenase complex subunit D [SDHD], succinate dehydrogenase complex subunit B [SDHB], ret proto-oncogene [RET], von Hippel-Lindau tumor suppressor [VHL], neurofibromatosis type-1). IV. To examine associations between tumor response and tumor expression levels of angiogenic and vascular markers including hypoxia inducible factor 1, alpha (HIF-1a), vascular endothelial growth factor receptor (VEGF-R) (total and phospho-) and microvessel density in archival tumor tissue. IV. To examine whether the extent of tumor response/regression may be correlated with plasma pazopanib (GW786034) concentration achieved after the third cycle (first cycle after run-in cycles) of pazopanib (GW786034) therapy. OUTLINE: This is a multicenter study. Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo urine and blood sample collection at baseline and periodically during study for correlative studies. After completion of study therapy, patients are followed up every 3-6 months for a maximum of 3 years.

PRIMARY OBJECTIVES:

     I. To evaluate in a Phase II study a preliminary estimate of the complete response (CR) rate of a new chemotherapy regimen involving Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) alternating with Pralatrexate (P) as front line therapy for patients with Stage II, III and IV Peripheral T-Cell NHL not otherwise specified (NOS), Anaplastic large cell lymphoma (ALK negative), Angioimmunoblastic T-cell lymphoma, Enteropathy associated T-cell lymphoma, Hepatosplenic gamma delta T-cell lymphoma followed by an optional stem cell transplant with high dose chemotherapy and Autologous stem cell transplant.

     SECONDARY OBJECTIVES:

     I. To evaluate partial response (PR). II. To evaluate overall response (CR+PR). III. To evaluate the safety and tolerability of the regimen. IV. To assess the 2 year event free survival (EFS) and overall survival (OS) using this regimen.

     V. To assess the percentage of patients who intended to receive transplant versus those who actually proceeded with transplant.

     VI. To evaluate the ability to collect peripheral blood stem cells after this regimen.

     OUTLINE:

     Patients receive cyclophosphamide intravenously (IV) and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or orally (PO) once daily (QD) on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

     Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

     After completion of study treatment, patients are followed up for 2 years (transplant patients) or periodically.