Minnesota Spinal Cord Injury Data Network
Minnesota Spinal Cord Injury Data Network
- ≥ 18 years of age.
- Presence of an external traumatic event that results in a spinal cord injury, including surgical procedures, radiation, and medical complications.
- Temporary or permanent loss of sensory and/or motor function as a result of the traumatic event.
- Admission to the database within one year of injury.
- If patient is discharged as Minimal Deficit or Recovered, they must be hospitalized in the system for at least one week before discharge.
- Discharge from the system as:
- Having completed inpatient acute rehabilitation;
- Achieving a neurologic status of normal or minimal deficit;
- Reside in the geographic catchment area of the system (greater Minnesota, Iowa, North Dakota, South Dakota, and western Wisconsin) at the time of the injury. Patients may be injured outside of the catchment area.
- A US citizen or non-US citizen who is expected to stay in the catchment area.
- Completion of an organized rehabilitation program prior to the admission to the system.
- Patients who are discharged as deceased.
The Application of Voice Enabled Artificial Intelligence for the Diagnosis of Hepatic Encephalopathy (Voice AI)
A Study to Evaluate Voice-enabled Artificial Intelligence to Diagnosis Hepatic Encephalopathy
- Male or female, age ≥ 18 years old.
- Having hepatic encephalopathy (HE).
- Are in the hospital (Methodist or St. Marys). Consented in an exam room or hospital room
- Must be able to carry on a conversation.
- Ability of subject or caregiver to provide written, informed consent. (LAR needed if subject is HE)
- Cirrhosis of any etiology.
- Individual < 18 years old.
- Known history of voice disorder or surgery that may alter voice characteristics.
- Smoking or vaping use currently or within the last 3 months
- Severe chronic obstructive pulmonary disease
- Inability to speak.
- Upper respiratory tract infection within the last week.
- Acute alcohol intoxication.
- VHI-10 score greater than 11.
- West Haven Criteria Grade 4.
Impact of Ketamine versus Propofol for Anesthetic Induction on Acute Kidney Injury and Renal Biomarkers in Cardiac Surgery (KKICS)
Ketamine and Kidney Injury in Cardiac Surgery
- Presenting for cardiac surgery at the Mayo Clinic in Rochester, Minnesota.
- Scheduled to undergo complex cardiac surgery with the use of cardiopulmonary bypass.
Complex cardiac surgery will be defined as surgery involving more than one heart
valve, redo-sternotomy procedures, or combined valvular and coronary artery bypass
graft procedures (aortic repair not excluded if meets other criteria).
- Left or right ventricular assist device implantation or explantation.
- Procedures not requiring cardiopulmonary bypass.
- Active infection or sepsis requiring antimicrobial therapy and/or vasopressor therapy
(treated endocarditis is not excluded).
- Severe hepatic disease resulting in ascites.
- Pre-operative significant renal dysfunction including a baseline creatinine equal to
or greater than 2 mg/dL or requiring dialysis.
- Immunosuppressive medication use (including current IV or oral steroids use, use of
anti-rejection medications for transplant within 1 month, or chemotherapy within 6
- Immunodeficiency syndrome including HIV/AIDS, leukemia, and multiple myeloma
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 2/15/23. Questions regarding updates should be directed to the study team contact.
AtriCure CryoICE Lesions for Persistent and Long-standing Persistent Atrial Fibrillation Treatment During Concomitant On-Pump Endo/Epicardial Cardiac Surgery (CP2018-1)
AtriCure CryoICE Lesions for Persistent and Long-standing Persistent Atrial Fibrillation Treatment
- Subject is greater than or equal to 18 years of age.
- Subject has history of persistent or long-standing persistent atrial fibrillation:
- AF documentation requirement for persistent AF: Physician’s note indicating continuous AF > 7 days but no more than 1 year, and electrocardiographic documentation showing continuous AF within 90 days of the ablation procedure. Documentation can include a 24- hour holter (or equivalent) or two ECGs taken at least seven days apart within 90 days of the ablation procedure;
- AF documentation requirement for longstanding persistent AF: physician’s note indicating at least 1 year of continuous AF, and electrocardiographic documentation showing continuous AF within 90 days of the ablation procedure. Documentation can include a 24- hour holter (or equivalent) or two ECGs taken at least seven days apart within 90 days of the ablation procedure. The performance of a successful cardioversion (sinus rhythm > 30 seconds) within 12 months of an ablation procedure with documented early recurrence of AF within 30 days should not alter the classification of AF as long-standing persistent.
- Stable Subject that is scheduled to undergo non-emergent cardiac surgical procedure(s) to be performed on cardiopulmonary bypass including open-heart surgery for one or more of the following: Mitral valve repair or replacement, Aortic valve repair or replacement, Tricuspid valve repair or replacement, Coronary artery bypass procedures, patent foramen ovale repair, and/or atrial septal defect.
- Left Ventricular Ejection Fraction ≥ 30% (determined by echocardiography or cardiac catheterization performed within 90 days of enrollment as documented in patient medical history).
- Subject is willing and able to provide written informed consent.
- Subject has a life expectancy of at least 5-years.
- Subject is willing and able to return for scheduled follow-up visits.
- Stand-alone AF without indication(s) for concomitant CABG and/or valve surgery.
- Previous surgical Maze procedure.
- Wolff-Parkinson-White syndrome or other Supra-Ventricular arrhythmia, AV nodal reentry.
- Prior cardiac surgery (Redo).
- Subjects requiring surgery other than CABG and/or cardiac valve surgery and/or patent foramen ovale repair, and/or atrial septal defect repair.
- Class IV NYHA heart failure symptoms.
- Prior history of cerebrovascular accident within 6 months or at any time if there is residual neurological deficit.
- Documented ST elevation MI within the 6 weeks prior to study enrollment.
- Need for emergent cardiac surgery (i.e., cardiogenic shock).
- Known carotid artery stenosis greater than 80%.
- Documented (continuous) AF duration of greater than ten years.
- LA diameter > 7 cm by TTE within 12 weeks (90 days) of procedure.
- Current diagnosis of active systemic infection.
- Severe peripheral arterial occlusive disease defined as claudication with minimal exertion.
- Renal failure requiring dialysis or hepatic failure.
- A known drug and/or alcohol addiction.
- Mental impairment or other conditions which may not allow the subject to understand the nature, significance and scope of the study.
- Pregnancy or desire to get pregnant within 12-months of the study treatment.
- Preoperative need for an intra-aortic balloon pump or intravenous inotropes.
- Requires anti-arrhythmic drug therapy for the treatment of a ventricular arrhythmia.
- Subjects who have been treated with thoracic radiation.
- Subjects in current chemotherapy.
- Subjects on long term treatment with oral or injected steroids (not including intermittent use of inhaled steroids for respiratory diseases).
- Subjects with known connective tissue disorders.
- Subjects with known hypertrophic obstructive cardiomyopathy.
- Subjects with known cold agglutinin.
- Patient has a condition that in the opinion of the investigator, may jeopardize the patient’s wellbeing and/or the soundness of this clinical study.
- Subject has a contraindication to post-operative anticoagulation; Patient has history of blood dyscrasia or clotting disorder (i.e., Idiopathic Thrombocytopenic Purpura [ITP] or Thrombotic Thrombocytopenic Purpura [TTP]).
Eligibility last updated 9/21/21. Questions regarding updates should be directed to the study team contact.
Developing Novel Tools for Determining Risk of Respiratory Complications Following Hematopoietic Stem Cell Transplant
A Study to Develop Novel Tools for Post-HCT Respiratory Complications
- Adult patients (age ≥ 18 years old).
- Undergoing evaluation for autologous or allogeneic bone marrow transplant (HCT) at Mayo Clinic Rochester.
- Scheduled for pre-HCT pulmonary function test by the primary team.
- Limited mobility requiring use of gait aid or wheelchair.
- Fall risk.
Impact of Menopause on Cardiac Stiffness Acquired with Magnetic Resonance Elastography
A Study to Evaluate the Impact of Menopause on Cardiac Stiffness Acquired with Magnetic Resonance Elastography
- Healthy, normal subjects around the approximate age of menopause (~ 51).
- In the 40-60 year age range without known cardiac conditions.
- Without symptoms referable to the heart, namely chest pain or shortness of breath.
- Subjects from the ongoing “Impact of Individualized Estrogen Therapy on Cardiovascular Disease Risk Parameters in Young Women after Bilateral Oophorectomy: A Randomized Controlled Trial” study.
- Subjects in this cohort will be between 21 and 45 years of age, at the onset of the study.
- Willingness to return for follow up exam +/- 3 weeks of 12 month post-operative follow-up appointment.
- These subjects will undergo two cardiac MRI/MRE exams one with-in +/- three weeks of their bilateral oophorectomy surgery and with-in +/- three weeks of their 12 month follow-up appointment.
- Known cardiac conditions, symptoms referable to the heart; namely, chest pain or shortness of breath.
- For Magnetic Resonance Imaging (MRI) participants:
- Absolute contraindications to MRI including pacemaker, AICD device, cochlear implant, VP shunt, aneurysm clip, deep brain stimulator, or severe claustrophobia;
- Body weight over 500 pounds (or 226 kilograms), and chest/waist/hip circumference over 160 cm, due to MRI system limit (70-cm bore, < 400 lbs.).
Hidradenitis Suppurativa Prospective Observational Registry and Biospecimen Repository- HS PROGRESS
Hidradenitis Suppurativa Registry
- Male or female, ≥ 10 years of age.
- Diagnosis of Hidradenitis Suppurativa (HS) by a dermatologist or practitioner experienced in making a diagnosis of HS.
- Written informed consent (and assent when applicable) obtained from subject or subject’s legal representative and ability for subject to comply with the requirements of the study.
- Immediate family members (for saliva and genetics data).
- Inability to give informed consent or unavailability of a parent/guardian who is able and willing to give informed consent.
Learning from Our Patients, Learning from Our Practice: Implementing an Intervention to Support Patients on Dialysis
Learning from Our Patients, Learning from Our Practice: Implementing an Intervention to Support Patients on Dialysis
- Clinicians employed at Mayo Clinic who provide care to patients visiting the Mayo Clinic Department of Nephrology and Hypertension Dialysis Services.
- Adult patients (18 years of age and older).
- Receive long-term dialysis treatment and services at Mayo Clinic.
- Minors (under the age of 18 years).
- Non-English speaking.
- Lack the ability to provide informed consent.
Evaluating the Need and Impact of a Multifaceted Wellness Program on the Health Related Quality of Life (HRQOL), Disease Activity, and Healthcare Utilization in Female Patients with Inflammatory Bowel Disease: Phase II – The Impact (IBD and WHC II)
IBD and Women's Health Intervention
- Female patient with a diagnosis of Ulcerative Colitis (UC) or Crohn’s Disease (CD) seen in the IBD clinic in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester.
- Who are between 18-64 years of age.
- Ability to provide informed consent.
- Ability to complete all aspects of this trial.
- Female patients with a diagnosis of UC or CD with medical co-morbidity or factor judged by the investigator to preclude participation in the study or which might hinder adherence.
- Participation in another organized wellness program.
A Comparative Quality of Life Assessment between Internal Endoscopic versus Percutaneous Drainage of Benign and Malignant Biliary Obstruction (QoL)
A Quality of Life Assessment of Patients with Biliary Obstruction Undergoing Endoscopic or Percutaneous Drainage
- Patients with benign biliary obstruction.
- Patients with malignant biliary obstruction.
- Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic biliary drainage (PTBD).
- Patients with gallstone disease.
- Patients who will undergo ERCP who currently have a percuteanous biliary drain placed.
- Patients who will undergo PTBD who currently have a biliary stent placed.
- Female patients who are pregnant.
- Prisoners and other vulnerable populations.
Eligibility last updated 10/12/21. Questions regarding updates should be directed to the study team contact.
A Pilot and Feasibility Trial of G-POEM for Gastroparesis to Assess Safety, Physiological Mechanisms and Efficacy (G-POEM)
A Study to Evaluate Safety and Effectiveness of G-POEM for Gastroparesis
- Symptoms of chronic nausea or vomiting compatible with gastroparesis (idiopathic or diabetic) must be present for at least one year (does not have to be contiguous) prior to registration.
- Must have a mean total Gastroparesis Cardinal Symptom Index (GCSI) score of ≥ 3 at screening visit.
- Refractory gastroparesis, defined using our previously published data5, as a failure to improve over the last 6 months, despite an adequate trial of one or more standard prokinetics (metoclopramide, erythromycin, prucalopride), antinauseants (5-HT3 antagonists, promethazine, prochlorperazine, dronabinol), or neuromodulators (mirtazapine, buspirone).
- Moderate to severe delay in gastric emptying, defined as > 25% solid retained at 4 hours or > 75%retained at 2 hours. The qualifying gastric emptying scintigraphy must be performed within 18 months prior to registration or can be the baseline gastric emptying.
- No evidence of mechanical obstruction based on upper GI endoscopy or upper GI series in their medical history.
- Another active disorder which could explain symptoms in the opinion of the investigator.
- Gastric retention of solids at 4 hours < 25% or < 75% at 2 hours.
- Ongoing use of prokinetic agents (e.g., metoclopramide, erythromycin, prucalopride) GLP -1 analog or agonists, or drugs that slow down gastric emptying (narcotics). Neuromodulators such as tricyclic antidepressants (amitriptyline or nortriptyline) or others that are being used at stable doses for a month prior to randomization may continue at the discretion of the care provider..
- Significant systemic illness such as chronic renal failure (adjusted for age) or liver disease as defined by Child-Pugh score of 10 or greater.
- Poorly controlled diabetes with HbA1c of greater than 10% at time of screening.
- New medications for gastroparesis-related symptoms started within 1 month prior to registration.
- Pregnancy or nursing.
- Failure to give informed consent.
- Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study.
- Botox injection into the pylorus within 3 months prior to registration.
- Allergy to eggs or Egg Beaters and Ensure.
Eligibility last updated 10/25/22. Questions regarding updates should be directed to the study team contact.
A Phase I Study of DS-8201a in Combination with Olaparib in HER2-Expressing Malignancies
A Study to Evaluate DS-8201a Combined with Olaparib in HER2-Expressing Cancers with Expansion in Endometrial Cancer Patients Testing the Combination of DS-8201a and Olaparib in HER2-Expressing Cancers With Expansion in Patients With Endometrial Cancer
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- Patients must have histologically confirmed uterine serous carcinoma with at least one lesion suitable for biopsy without significant risk to the patient. Patient disease must be evaluable or measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Biopsiable lesion can be same as evaluable lesion.
- Patients must have had at least one prior line of cytotoxic chemotherapy. Patients can have received an unlimited number of additional lines of chemotherapy, targeted therapy, biologic therapy, or hormonal therapy
- Patients must have HER2-positive or HER2-expressing tumors determined by a CLIA-certified laboratory. Specific requirement of HER2 status is outlined below:
- HER2 1-3 + expression by IHC; OR
- HER2 amplification by next generation sequencing panel (NGS) or in situ hybridization (ISH); OR
- If local testing is not feasible, patients will submit archival tissue for central HER2 testing to determine eligibility. Patients with unknown or negative HER2 testing will not be eligible.
- Patients must have archival FFPE tissue available for central confirmation of HER2 testing.
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of DS-8201a in combination with olaparib in patients < 18 years of age, children are excluded from this study.
- ECOG performance status ≤ 1 (Karnofsky ≥ 70%).
- Patients must have adequate organ and marrow function within 14 days of randomization/enrollment as defined below:
- Hemoglobin ≥ 10.0 g/dL;
- Absolute neutrophil count ≥ 1,000/mcL**;
- Platelets ≥ 100,000/mcL*;
- Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), (< 3 × ULN in the presence of documented Gilbert’s syndrome or liver metastases at baseline);
- AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN;
- International Normalized ratio ≤ 1.5 × ULN (INR)/Prothrombin time (PT) and activated partial thromboplastin time (aPTT);
- Creatinine ≤ 1.5 × institutional ULN OR;
- Glomerular filtration rate (GFR) ≥ 51 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2).
- *No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment.
- **No administration of G-CSF is allowed within 1 week prior to screening assessment.
- Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization/enrollment.
- Patients who are Human Immunodeficiency Virus (HIV) positive may participate IF they meet the following eligibility requirements:
- They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective.
- They must have an undetectable viral load and a CD4 count ≥ 250 cells/µL within 7 days of enrolment.They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months.
- HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Patients with brain metastases should be stable and off steroids and at least 4 weeks from radiation at the time of registration.
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be better than class 2B.
- The effects of DS-8201a and olaparib on the developing human fetus are unknown. For this reason and because HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as PARP inhibitors are known to be teratogenic; thus, women of childbearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 7 months (WOCBP only) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of DS-8201a and olaparib administration. For methods considered as highly effective methods of contraception.
- Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [<147 pmol/L] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study.
- Female subjects must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.
- Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible.
- Patients who have had chemotherapy (including antibody drug therapy) within 4 weeks with the following exceptions: 1 week for weekly paclitaxel; 2 weeks or five half-lives, whichever is longer, for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents, hormonal agents; or 6 weeks for nitrosoureas or mitomycin C.
- Patients who have had radiation therapy within 4 weeks.
- Patients who have had a major surgery within 4 weeks.
- Patients who are receiving any other investigational agents.
- For the dose expansion cohort: Patients who have received prior PARP inhibitors.
- Patients with a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to DS-8201a, the inactive ingredients in the drug product, olaparib, or severe hypersensitivity to other monoclonal antibodies.
- Patients receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
- Patients with a medical history of myocardial infarction within 6 months before randomization/enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class IIb to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to randomization.
- Patients with a corrected QT interval (QTc) prolongation to > 470 ms (females) or > 450 ms (males) based on average of the screening triplicate 12-lead ECG.
- Patients with clinically significant corneal disease in the opinion of the Investigator.
- Patients with multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, and other solid tumors curatively treated.
- Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
- Patients receiving chloroquine or hydroxychloroquine will require a washout period of ≥ 14 days to be eligible for the study.
- Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤ 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee (e.g., grade 2 chemotherapy-induced neuropathy).
- Patients with psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a. These potential risks may also apply to other agents used in this study.
Eligibility last updated 8/26/21. Questions regarding updates should be directed to the study team contact.
EvALuation of ECG transmission and AI moDels using Apple watch ECGs and Symptoms data collected usiNg a Mayo iPhone App (ALIGN)
EvALuation of ECG transmission and AI models using Apple watch ECGs and symptoms data collected usiNg a Mayo iPhone App
- Adult patients, ≥ 18 years of age.
- Using the Mayo patient iPhone app. (determined automatically via Mayo software).
- Inability to provide informed consent.
- Age under 18 years.
A Randomized Double-Blind, Placebo Controlled Trial of Abatacept (CTLA4-Ig) in Giant Cell Arteritis (ABAGART) (ABAGART)
A Study to Evaluate Abatacept to Treat Giant Cell Arteritis
- A diagnosis of newly-diagnosed or relapsing Giant Cell Arteritis (GCA).
- Diagnostic criteria for GCA.
- A patient will be said to have GCA by meeting 3 of 5 of the following modified ACR criteria for the classification of GCA in which 1 of the 3 must consist of criteria 4 or 5:
- Age at disease onset ≥ 50 years;
- New onset or new type of localized pain in the head;
- ESR of > 40 mm in the first hour by the Westergren method or CRP measurement above the laboratory normal limit;
- Temporal artery abnormality (i.e., temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries);
- Temporal artery or large vessel biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant celor an abnormal temporal artery ultrasound showing features consistent with active giant cell arteritis (“halo sign”) or characteristic changes of large vessel stenosis or aneurysm by arteriography.
- GCA with evidence of active disease (defined below) present within the past 8 weeks.
- They must be willing and able to comply with treatment and follow-up procedures.
- Both women and men who are of child-bearing potential must be willing to use an effective means of birth control while receiving treatment through this study. Effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal contraception.
- Must be willing and able to provide written informed consent.
- Evidence of a recent acute infection defined as:
- Any acute infection within 60 days prior to randomization that required hospitalization or treatment with parenteral antibiotics.
- Any acute infection within 30 days prior to randomization that required oral antimicrobial or antiviral therapy.
- Patients with history of chronic or recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis etc.).
- Patients with a history of recurrent herpes zoster (more than 1 episode) or disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic zoster. Symptoms of herpes zoster or herpes simplex must have resolved more than 60 days prior to screening.
- Patients with a history of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis).
- Patients with a history of primary immunodeficiency.
- Patients at risk for tuberculosis (TB) defined as follows:
- Current clinical, radiographic or laboratory evidence of active TB, even if currently being treated. Chest x-rays (posterior/anterior and lateral) obtained within the 6 months prior to screening and TB testing (IFN- gamma release assay or PPD) performed in the past month prior to screening will be accepted; however, a copy of the reports must be placed in the participant binder;
- A history of active TB unless there is documentation that the patient had received prior anti-TB treatment that was appropriate in duration and type according to local health authority guidelines;
- Patients with a positive TB screening test indicative of latent TB will not be eligible for the study unless they:
- Have no evidence of current TB based on chest x-ray performed during the screening period and by history and physical exam, and
- They are currently being treated for latent TB or the site has documentation of successful prior treatment of latent TB. Treatment regimens should be dictated by local guidelines as long as the treatment dose and duration meet or exceed local health authority guidelines. If permitted by local guidelines regarding treatment with biologic medications, patients with latent TB may be randomized prior to completion of treatment as long as they have completed at least 4 weeks of treatment and they have no evidence of current TB on chest x-ray at screening.
- Patients who are pregnant or who are nursing infants.
- Inability to comply with study guidelines.
- Cytopenia: platelet count < 80,000/mm³, total White Blood Count (WBC) < 3,000/mm³ (3 x 10⁹/L) absolute neutrophil <1500/mm³, hematocrit < 20%.
- Renal insufficiency defined by a creatinine clearance of less than or equal to 20 ml/min.
- AST or ALT > 3 times above normal laboratory range.
- Other severe, progressive, or uncontrolled disease that in the investigator’s opinion could prevent a patient from fulfilling the study requirements or that would increase the risk of study participation.
- Patients who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Patients who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.
- Receipt of an investigational agent or device within 30 days prior to enrollment.
- A live vaccination within 3 months before randomization.
- Patients on non-biologic immunosuppressants must discontinue these medications before randomization (azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide, hydroxychloroquine, cyclosporin, tacrolimus, or other conventional immunosuppressive agent).
- Patients who had received an alkylating agent such as cyclophosphamide must discontinue these medications at least 8 weeks before randomization.
- Patients who have been treated within 4 weeks of randomization with etanercept or within 8 weeks with adalimumab, certolizumab, golimumab, or infliximab.
- Patients who have been treated within 8 weeks of randomization with anti-IL-6 agents (e.g., tocilizumab, sirukumab) or a janus kinase inhibitor.
- Patients who have been treated within 4 weeks of randomization with anakinra.
- Patients who have received prior treatment with rituximab within the past 6 months prior to randomization.
- Patients who have received prior treatment with abatacept or CTLA4-Ig.
- Patients who will require oral or IV glucocorticoid treatment during the trial for conditions other than GCA.
- Hypersensitivity to abatacept and/or its excipients.
- Presence of any of the following disease processes:
- Takayasu arteritis;
- Granulomatosis with polyangiitis;
- Microscopic polyangiitis;
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss);
- Polyarteritis nodosa;
- Cogan’s syndrome;
- Behçet’s disease;
- Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics vasculitis;
- Cryoglobulinemic vasculitis;
- Systemic lupus erythematosus;
- Rheumatoid arthritis;
- Mixed connective tissue disease or any overlap autoimmune syndrome.
Remote Monitoring in Cancer Care: A Platform Study
A Study to Evaluate Remote Monitoring in Cancer Care
- Age ≥ 18 years.
- Provide written informed consent.
- Patients undergoing commercial CAR-T cell therapy in an outpatient setting.
- Individuals < 18 years of age.
- Non-English speaking.
- Planned initiation of lymphodepleting chemotherapy in the inpatient setting.
Optimizing Pancreatic Cancer Management with Next Generation Imaging and Liquid Biopsy
Optimizing Pancreatic Cancer Management Using Next Generation Imaging and Liquid Biopsy
- Adults ≥ 18 years with treatment-naïve biopsy-proven PDA or with findings diagnostic for PDA on baseline imaging (CT, MRI or PET).
- Localized disease expected to undergo surgical resection following NAT.
- ECOG performance status of 0-2.
- Ability to provide informed consent.
- Non-PDA histology on biopsy.
- No baseline PET/CT or PET/MRI.
- Histopathologically proven metastatic PDA.
- Non-FDG avid PDA on baseline PET/CT or PET/MRI.
- Pregnant women.
Eligibility last updated8/25/21. Questions regarding updates should be directed to the study team contact.
SLEep Apnea in Heart Failure with Preserved Ejection Fraction - Exercise Capacity and Impact of Positive Airway Pressure Therapy (SLEEP-HFpEF)
A Study to Evaluate Exercise Capacity and Positive Airway Pressure Impact on Sleep Apnea in Heart Failure
- Age ≥ 18 years.
- Diagnosis of HFpEF by catheterization with resting PCWP > 15 mmHg or exercise PCWP > 25 mmHg.
- If no known diagnosis of OSA, must not be pacemaker dependent with with either atrial pacing or VVI without sinus rhythm.
- If no known diagnosis of OSA, must be able to temporarily hold nitrates or alpha channel blockers for home WatchPAT testing.
- Ejection fraction < 40%.
- Obstructive hypertrophic cardiomyopathy.
- Constrictive pericarditis or tamponade.
- Active myocarditis.
- Complex congenital heart disease.
- Other valve disease requiring surgical intervention.
- Terminal illness (other than HF) with expected survival of less than 1 year.
- Inability to comply with planned study procedures.
- Pregnancy or breastfeeding mothers.
Eligibility last updated 5/9/22. Questions regarding updates should be directed to the study team contact.
Phase 2 Lymphoma Epidemiology of Outcomes Cohort - Central IRB (LEO 2.0)
A Study to Evaluate Lymphoma Epidemiology
- Patients must be newly diagnosed within 6 months (180 days) of enrollment.
- Patients may have been treated as long as initial non-Hodgkins Lymphoma (NHL) or Hodgkin's Lymphoma (HL) diagnosis is within 6 months of enrollment.
- Patients must be 18 years or older.
- Patients will be recruited regardless of human immunodeficiency virus (HIV) status.
- Patients less than 18 years of age.
Validation of Shear Wave Elastography and 3D Ultrasound as Surrogate Measurement of Tissue Properties and Injury Diagnostic Tool for the ACL
Ultrasound as Surrogate Diagnostic Tool for ACL Injury
- Subjects recruited for the injured limb cohort may be dual-recruited as controls so long as their contralateral limb satisfies the inclusion criteria.
- Age between 14-40 years old.
- No history of prior knee trauma or knee surgery.
- No hard tissue structural damage to the knee joint concomitant to the ACL injury.
- No abnormality that adversely impacts standard function of the knee. For the injured cohort, an acute ACL injury confirmed by MRI is required.
- For the healthy cohort, no history of structural knee damage in the target limb is required.
- Less than 14 and over 40 years of age.
Characterization of microvasculature in kidney transplant by super-resolution ultrasound imaging
Ultrasound Microvessel Imaging of Transplant Kidney
- Male and female patients.
- Age ≥ 18 years old.
- Having transplant kidney and undergoing clinically indicated allograft biopsy.
- Able and willing to consent.
- Patients lacking capacity to consent.
- Vulnerable subjects such as prisoners, pregnant women, nursing mothers.
- Subjects with history of hypersensitivity allergic reactions to ultrasound contrast agents.
A First In Human Evaluation of a Novel Approach to Painless Cardioversion (NAPC) in Patients with Atrial Fibrillation (MediCool)
- Subject must be ≥ 18 years or older.
- Male or female.
- Subject has documented paroxysmal, or persistent atrial fibrillation (AF) with a history of less than one-year duration.
- Must be in AF at time of surgery, or inducible using manual or electrical stimulation.
- Subject is willing and able to provide written informed consent.
- Subject has a life expectancy of at least 1 year.
- Long-standing AF (duration > 1 year).
- Prior AF ablation.
- Left main coronary artery occlusion > 70%.
- Critical aortic stenosis (gradient > 50mm HG).
- Inability to induce patient into AF without drugs at time of surgery.
- Female subjects who are pregnant at time of surgery.
- Subjects with a medical condition or comorbidity that could adversely impact study participation, safety or conduct of the study.
- Permanent pacemaker or implantable cardioverter defibrillator.
- Current cancer treatment that includes radiation of the heart.
- Inability to give informed consent.
Mayo MRI White-Matter-Nulled Imaging Study (START MRI)
Mayo MRI White-Matter-Nulled Imaging Study
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, 18 years of age or older.
- In good general health as evidenced by medical history but may include a diagnosis of epilepsy.
- Volunteers who are confirmed to have temporal lobe epilepsy based on established medical history and have established outpatient epilepsy care within the Mayo Clinic Health System.
- Participants with a contraindication to MRI. Such contraindications include, but are not limited to: pacemaker, metallic cardiac valve(s), magnetic material such as surgical clips, tattoos, implanted electronic infusion pumps or any other condition that would interfere with the MRI, a stent somewhere in the body, a history of allergic reaction to any metals.
- Participants who have structural anatomical legions outside the medial temporal lobe.
- Pregnancy or lactation.
- Participants who report previous experience with claustrophobia, anxiety and/or vertigo when moved inside the scanner.
- Febrile illness within the last thirty days.
- Treatment with another investigational drug or other intervention within the last thirty days.
- Subjects incapable of giving informed written consent.
- Participants in the prisoner population.
Eligibility last updated 8/26/21. Questions regarding updates should be directed to the study team contact.
M-2018-344, A Multi-center Single-arm Phase II Study to Evaluate the Safety and Efficacy of Genetically-engineered Autologous Cells Expressing Anti-CD20 and Anti-CD19 Specific Chimeric Antigen Receptor in Subjects with Relapsed and/or Refractory Diffuse Large B Cell Lymphoma
A Study to Evaluate the Safety and Effectiveness of Autologous Cells Expressing Anti-CD20 and Anti-CD19 in Relapsed/Refractory Diffuse Large B Cell Lymphoma Patients
- Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification:
- DLBCL not otherwise specified (NOS);
- High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements;
- High-grade B cell lymphoma, NOS o Primary mediastinal (thymic) large B cell lymphoma;
- Transformed lymphoma (e.g., transformed follicular or marginal zone lymphoma, follicular lymphoma Grade 3).
- Relapsed or refractory disease after 2 or more lines of chemotherapy including rituximab and anthracycline and either having failed autologous stem cell transplant (ASCT), or being ineligible for or not consenting to ASCT 2.1.
- Chemotherapy-refractory disease is defined as one of the following:
- No response to last line of therapy:
- Progressive disease (PD) as best response to most recent therapy regimen o Stable disease (SD) as best response to most recent therapy with duration no longer than 6 months from last dose of therapy; OR
- Relapsed or persistent disease after prior ASCT for lymphoma;
- Disease progression or relapse less than or equal to 12 months of ASCT;
- If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.
- Disease relapse in subjects without prior ASCT is defined as relapse of disease in ≤ 12 month after the last dose of most recent therapy regimen.
- Ineligible for ASCT is defined as meeting one of the following criteria:
- Chemotherapy-refractory disease after salvage therapy;
- Disease progression or relapse ≤ 12 months after salvage therapy;
- Intolerance to salvage therapy.
- In addition, all subjects must have:
- Age ≥ 18 years;
- Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to DLBCL;
- Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma (Cheson et al, 2014);
- CD19 or CD20 antigen expression on tumor is not required after the most recent chemoimmunotherapy; however:
- Subject must have at least 10 unstained slides of tissue available prior to MB-CART2019.1 infusion;
- If archival tissue is not available, subject must be willing to undergo attempted repeat biopsy.
- No clinical suspicion of central nervous system (CNS) lymphoma.
- If the subject has history of CNS disease, then he/she must:
- Have no signs or symptoms of CNS disease;
- Have no active disease on magnetic resonance imaging (MRI);
- Have no large cell lymphoma present in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells (WBCs).
- If has history of cerebral vascular accident (CVA):
- The CVA event must be greater than 12 months prior to leukapheresis;
- Any neurological deficits must be stable.
- A creatinine clearance (as estimated by direct urine collection) > 60mL/min.
- Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA).
- Resting O2 saturation > 90% on room air.
- Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) 1000/μL.
- Absolute lymphocyte count > 100/μL.
- Platelet count > 50,000/µL.
- Estimated life expectancy of more than 3 months other than primary disease.
- Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study.
- Primary CNS lymphoma.
- Richter’s transformed DLBCL arising from chronic lymphocytic leukemia (CLL).
- Unable to give informed consent.
- Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive), unless confirmed to be polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive.
- Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing
- Known history of active seizure or presence of seizure activities or on active anti-seizure medications within the prior 12 months.
- Known history of CVA within prior 12 months.
- Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease.
- Presence of active CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity.
- Active systemic fungal, viral or bacterial infection.
- Pregnant or breast-feeding woman.
- Previous or concurrent malignancy with the following exceptions:
- Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry);
- In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study;
- Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years;
- A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years.
- History of non-neurologic autoimmune disease (e.g., Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus) requiring systemic immunosuppressive or systemic disease modifying agents within the last 2 years.
- Medical condition requiring prolonged use of systemic corticosteroids equivalent to Prednisone > 10 mg/day.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment.
- Concurrent radiotherapy (allow up to time of leukapheresis).
- Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Refusal to participate in additional lentiviral gene therapy long-term follow-up (LTFU) protocol.
- Prior CAR-T therapy for any indication.
- Prior allogeneic stem cell transplant for any indication.
- Prior Bispecific T cell engaging (BITE) antibodies for cancer therapy.
- Prior T cell receptor-engineered T cell therapy.
A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321) (BRUIN-MCL-321)
A Study to Evaluate LOXO-305 Vs. Approved BTK Inhibitor Approved Drugs to Treat Patients with Mantle Cell Lymphoma
- Confirmed MCL diagnosis
- Previously treated with at least one prior line of systemic therapy for MCL
- Measurable disease per Lugano criteria
- Eastern Cooperative Oncology Group (ECOG) 0-2
- Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor
support within 7 days of screening
- Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 7 days
- Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 7
days of screening.
- AST and ALT ≤ 3.0 x upper limit of normal (ULN).
- Total bilirubin ≤ 1.5 x ULN.
- Creatinine clearance of ≥ 30 mL/min according to Cockcroft/Gault Formula
- Prior treatment with an approved or investigational BTK inhibitor
- History of bleeding diathesis
- History of stroke or intracranial hemorrhage within 6 months of randomization
- History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen
receptor modified T-cell (CAR-T) therapy within 60 days of randomization
- Clinically significant cardiovascular disease
- Prolonged QT interval corrected using Fridericia's formula (QTcF) > 470 ms on 2/3
consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs
- Known HIV infection or active HBV, HCV, or CMV infections
- Clinically significant active malabsorption syndrome or other condition likely to
affect gastrointestinal (GI) absorption
- Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy
prior to start of study drug treatment.
- Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K
- Vaccination with live vaccine within 28 days prior to randomization
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 6/29/22. Questions regarding updates should be directed to the study team contact.
A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects with Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy (Vedo UC)
A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Ulcerative Colitis
1. Has moderately to severely active UC, unresponsive or intolerant to their current
standard of care (SOC).
2. Weighs ≥10 kg at the time of screening and enrollment into the study.
3. Has moderately to severely active UC diagnosed at least 1 month before screening,
defined by a modified Mayo score of 5 to 9 (sum of Mayo endoscopic subscore, stool
frequency subscore, and rectal bleeding subscore) with a Mayo endoscopic subscore of
≥2 (with the presence of mucosal friability excluding an endoscopic subscore 1 and
mandating a score of at least 2).
4. Has failed, lost response to, or been intolerant to treatment with at least 1 of the
following agents: corticosteroids (eg, azathioprine [AZA], 6-mercaptopurine [6-MP],
methotrexate [MTX]), immunomodulators, and/or tumor necrosis factor alpha (TNF-?)
antagonist therapy (eg, infliximab, adalimumab). This includes participants who are
dependent on corticosteroids to control symptoms and who are experiencing worsening of
disease in the moderate-to-severe range when attempting to wean off corticosteroids.
5. Has evidence of UC extending proximal to the rectum (i.e., not limited to proctitis),
at a minimum.
6. Has extensive colitis or pancolitis of >8 years' duration or left-sided colitis of >12
years' duration must have documented evidence of a negative surveillance colonoscopy
within 12 months before screening.
7. Participants with vaccinations that are up-to-date based on the countrywide, accepted
schedule of childhood vaccines.
1. Has previous exposure to approved or investigational anti-integrins including, but not
limited to natalizumab, efalizumab, etrolizumab, or Abrilumab (AMG 181), or mucosal
addressin cell adhesion molecule-1 (MAdCAM-1) antagonists or rituximab.
2. Has received an investigational biologic within 60 days or 5 half-lives before
screening (whichever is longer); or an approved biologic or biosimilar agent within 2
weeks before the first dose of study drug or at any time during the screening period.
3. Has active cerebral/meningeal disease, signs/symptoms or history of progressive
multifocal leukoencephalopathy (PML) or any other major neurological disorders
including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
4. Has had clinically significant infection (eg, pneumonia, pyelonephritis, coronavirus
disease 2019 [COVID-19]) within 30 days prior to first dose of study drug.
5. Has received any live vaccinations within 30 days prior to first dose of study drug.
6. Participants who currently require surgical intervention or are anticipated to require
surgical intervention for UC during this study.
7. Has had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy,
ileo-anal pouch, or known fixed stenosis of the intestine.
8. Participants with a current diagnosis of indeterminate colitis.
9. Participants with clinical features suggesting monogenic very early onset inflammatory
10. Participant with active or latent tuberculosis (TB), as evidenced by a diagnostic TB
test performed within 30 days of screening or during the screening period that is
positive, defined as:
- Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR
- A TB skin test reaction ≥5 mm. NOTE: If participants have received Bacillus
Calmette-Guérin vaccine then a QuantiFERON TB Gold test should be performed
instead of the TB skin test.
11. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus infection.
- HBV immune participants (ie, being hepatitis B surface antigen negative and
hepatitis B antibody positive) may be included, however.
12. The participant has evidence of dysplasia or history of malignancy other than a
successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma or
localized carcinoma in situ of the cervix.
13. Has positive stool studies for ova and/or parasites or stool culture at screening
14. Has positive Clostridium difficile stool test at screening visit.
Eligibility last updated 7/8/22. Questions regarding updates should be directed to the study team contact.
A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects with Moderately to Severely Active Crohn’s Disease Who Achieved Clinical Response Following Open–Label Vedolizumab Intravenous Therapy (Vedo CD)
A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Crohn's Disease (CD)
- Subjects male or female aged 2 to 17 years, inclusive, who weigh ≥ 10 kg at the time of screening and enrollment into the study.
- Subjects with moderately to severely active CD diagnosed at least 1 month before screening, defined by a PCDAI > 30 and an SES-CD > 6 (or an SES-CD ≥ 4 if disease is confined to terminal ileum).
- Subjects who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents:
- corticosteroids, immunomodulators (eg, AZA, 6-mercaptopurine, methotrexate), and/or TNF-α antagonist therapy (e.g., infliximab, adalimumab). This includes subjects who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition.
- Subjects with extensive colitis or pancolitis of > 8 years’ duration or left-sided colitis of > 12 years’ duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening.
- Subjects with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.
- Subjects who have had previous exposure to approved or investigational anti-integrins, including but not limited to natalizumab, efalizumab, etrolizumab, or AMG 181, or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists or rituximab.
- Subjects who have had prior exposure to vedolizumab.
- Subjects with hypersensitivity or allergies to any of the vedolizumab excipients.
- Subjects who have received either:
- an investigational biologic within 60 days or 5 half-lives before screening (whichever is longer); or
- an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period.
- Subjects with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
- Subjects who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study.
- Subjects who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or > 3 small intestine resections.
- Subjects with a current diagnosis of indeterminate colitis.
- Subjects with clinical features suggesting monogenic very early-onset inflammatory bowel disease.
Phase I/II Combination Study of NMS-03305293 and Temozolomide in Adult Patients with Recurrent Glioblastoma (NMS-03305293)
A Study to Analyze NMS-03305293 and Temozolomide in Adult Patients with Recurrent Glioblastoma
- Phase 1 (except for glioblastoma expansion cohort)
1. Histologically confirmed diagnosis of an intracranial diffuse glioma (i.e. diffuse
astrocytoma, oligodendroglioma or glioblastoma).
2. Patients at first relapse after chemotherapy including temozolomide as long as no more
than 12 cycles of temozolomide were administered.
- Phase 2 and Phase 1 glioblastoma expansion cohort
1. Histologically confirmed diagnosis of IDH wild type glioblastoma as per WHO 2016
classification or c-IMPACT-NOW 3 definition including diffuse astrocytic glioma,
IDH-wildtype, with molecular features of glioblastoma, WHO Grade 4. IDH1 status must
be assessed locally by immunohistochemistry (IHC). If IHC is performed and is
negative, and patient is < 55 years old, sequencing or a PCR-based validated test must
be performed to exclude other IDH1 or IDH2 most frequent mutations.
2. Patients at first relapse after initial standard therapy including temozolomide as
long as no more than 6 cycles of temozolomide were administered and provided that
patient completed standard of care concurrent temozolomide and the radiation therapy.
- Phase 1 and Phase 2
3. Patients may have been operated for recurrence. If operated:
- residual and measurable disease after surgery is not required but pathology must
have confirmed tumor recurrence.
- a post-surgery MRI should be available within 48 hours following surgery.
- surgery completed at least 2 weeks before enrolment/randomization and patient
should have fully recovered.
4. For non-operated patients, recurrent disease must be defined by at least one
bidimensionally measurable contrast-enhancing lesion with clearly defined margins with
minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on MRI
scan done within two weeks prior to enrolment/randomization.
5. Patients on steroids should have stable or decreasing dose of steroids for 7 days
prior to the baseline MRI scan.
6. Life expectancy of at least 3 months.
7. Able to undergo brain MRI scans with IV gadolinium.
8. No evidence of symptomatic and acute intratumoral hemorrhage on MRI. Patients with MRI
demonstrating old hemorrhage or subacute blood after a neurosurgical procedure (biopsy
or resection) are eligible.
9. Sufficient tissue representative of the disease available for central MGMT promoter
methylation status (Phase 1 and 2) and IDH status evaluation (Phase 1).
10. Male or female patients with age ≥ 18 years.
11. ECOG performance status ≤ 2.
12. Signed and dated IEC or IRB-approved Informed Consent.
13. Resolution of all acute toxic effects (excluding alopecia) of any prior anticancer
therapy to NCI CTCAE (Version 5.0) Grade ≤ 1 or to the baseline laboratory values as
defined in Inclusion Criterion Number 14.
14. Baseline laboratory values fulfilling the requirements declared into the Protocol
15. Patients must use effective contraception or abstinence. Female patients of
childbearing potential must agree to use effective contraception or abstinence during
the period of therapy and in the following 6 months after discontinuation of study
treatment. Male patients must be surgically sterile or must agree to use effective
contraception or abstinence during the period of therapy and in the following 6 months
after discontinuation of study treatment.
16. Ability to swallow capsules intact (without chewing, crushing, or opening).
17. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests and other study indications or procedures.
1. Current enrollment in another interventional clinical trial.
2. Current treatment with other anticancer agents, or treatment at recurrence with
carmustine wafer implants and proteasome inhibitors.
3. Previous treatment with PCV (procarbazine, lomustine and vincristine) or any of its
components, carmustine wafer implants, or bevacizumab.
4. Previous treatment with PARP inhibitors.
5. Major surgery, other than surgery for recurrent diffuse glioma, within 4 weeks prior
6. Standard radiotherapy within the three months (12 weeks) prior to the diagnosis of
progression unless the progression is clearly outside the radiation field (eg, beyond
the high-dose region or 80% isodose line) or unless the recurrence is histologically
7. Prior radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy,
unless the recurrence is histologically proven.
8. Use of full-dose anticoagulants unless the INR or aPTT is within therapeutic limits
(according to the medical standard in the institution) and the patient has been on a
stable dose of anticoagulants for at least two weeks before enrollment (Phase 1) or
randomization (Phase 2).
9. Treatment with concomitant medications known to be sensitive substrates of CYP2D6 and
CYP2C19 that cannot be replaced with another treatment.
10. Treatment with enzyme-inducing anti-epileptic drugs (EIAED). Patients may be on
non-EIAED or not be taking any anti-epileptic drugs. Patients previously on EIAED must
be fully switched to non-EIAED at least 2 weeks prior to enrolment/randomization.
11. Pregnant or breast-feeding women.
12. Known hypersensitivity to any component of NMS-03305293 or TMZ (Phase 1, Phase 2) or
lomustine (Phase 2) drug formulations.
13. Known active infections (bacterial, fungal, viral including HIV positivity) requiring
14. Patients with QTc interval ≥480 milliseconds or with risk factors for torsade de
pointes (e.g., uncontrolled heart failure, uncontrolled hypokalemia, history of
prolonged QTc interval or family history of long QT syndrome). For patients receiving
treatment with concomitant medications known to prolong the QTc interval, replacement
with another treatment should be considered. If replacement is not possible, a careful
risk/benefit evaluation should be performed prior to enrollment.
15. Active gastrointestinal disease (e.g., documented gastrointestinal ulcer, Crohn's
disease, ulcerative colitis, or short gut syndrome) or other syndromes that would
impact on drug absorption.
16. Planned vaccinations with live vaccines (Phase 2).
17. Any of the following in the past 6 months: myocardial infarction, unstable angina,
coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
cerebrovascular accident or transient ischemic attack, active bleeding disorder.
18. Prior invasive malignancy (except for non melanoma skin cancer, carcinoma in situ of
the cervix or localized cancer) unless the patient has been disease-free and off
therapy for that disease for ≥ 3 years.
19. History of coeliac disease and wheat allergy (Phase 2).
20. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration or may interfere with the interpretation of study results and, in
the judgment of the Investigator, would make the patient inappropriate for entry into
this study or could compromise protocol objectives in the opinion of the Investigator
and/or the Sponsor.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 3/14/23. Questions regarding updates should be directed to the study team contact.
Renal Anhydramnios Fetal Therapy (RAFT) Study (RAFT)
A Study to Analyze the Renal Anhydramnios Fetal Therapy (RAFT)
- Confirmed anhydramnios before 22 weeks GA for patients with FRF or confirmed diagnosis of CoBRA.
- Anhydramnios in the absence of ruptured membranes (ROM) on ultrasound.
- No significant bladder filling on ultrasound.
- Consent is signed and first therapeutic amnioinfusion can and does occur before 26 weeks and 0 days gestational age.
- Confirmation that the expectant mother does not wish to undergo termination of the pregnancy.
- Age ≥ 18 years of age for expectant mothers.
- Willingness to be followed and deliver at a RAFT center.
- Willingness for postnatal care to be performed at a RAFT center until discharge.
- Completed consults with Pediatric Nephrology, Neonatology, Transplant Surgery, Pediatric surgery, Maternal-Fetal Medicine Specialist, and Licensed Clinical Social Worker and a Genetic Counselor.
- Cervix less than 2.5 cm in length.
- No significant pathogenic or likely significant pathogenic findings on Karyotype or Microarray.
- Other significant congenital anomalies in the fetus.
- Evidence of chorioamnionitis or abruptio placentae.
- Evidence of rupture of membranes or chorioamniotic separation.
- Evidence of preterm labor.
- Multiple gestation.
- Severe maternal medical condition in pregnancy.
- Maternal depression as assessed by a Beck Depression Inventory score equal to or greater than 17 that is refractory to treatment.
- Technical limitations precluding amnioinfusion.
ACNS1931, A Phase 3 Study of Selumetinib (NSC# 748727, IND# 77782) or Selumetinib in Combination with Vinblastine for non-NF1, non-TSC Patients with Recurrent or Progressive Low-Grade Gliomas (LGGs) Lacking BRAFV600E or IDH1 Mutations (ACNS1931)
A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
- Patients must be ≥ 2 years and ≤ 25 years of age at the time of enrollment on Step 0.
- All patients > 21 years of age at the time of enrollment must have had initial diagnosis of low-grade glioma by 21 years of age.
- Patient is suspected of having progressive or recurrent low-grade glioma (LGG).
- Patient does not have a known diagnosis of neurofibromatosis type 1 (NF1) or tuberous sclerosis complex (TSC).
- Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
- Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following exceptions:
- Patients must not have had progressive disease while on therapy with vinblastine or a MEK inhibitor;
- Patients must not have discontinued vinblastine or selumetinib due to toxicity.
- Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year.
- Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals Grade I/II histology.
- Patients may not be receiving any other investigational agents.
- Patients must not have known hypersensitivity to selumetinib, vinblastine, or similar compounds.
- CYP3A4 Agents: Patients must not have received fluconazole or drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment.
- Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment.
- Patients who, in the opinion of the investigator, are not able to comply with the study procedures.
- Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy, placement of a vascular access device or CSF diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
- Note: Patients must have healed from any prior surgery.
- Patients who have an uncontrolled infection.
- Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Lactating females who plan to breastfeed their infants.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy.
- Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo.
Comorbid Insomnia and Sleep Disordered Breathing in Patients Undergoing Cardiac Rehabilitation: Prevalence and Impact on Cardiovascular Risk Profile
A Study to Evaluate Comorbid Insomnia and Sleep Disordered Breathing in Patients Undergoing Cardiac Rehabilitation
- Patients ≥ 18 years old.
- Referred to cardiac rehabilitation (CR) following admitted to the hospital with a documented diagnosis of acute coronary syndrome, including ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina, or post coronary artery bypass surgery or after percutaneous coronary intervention (with or without stent placement).
- Patients < 18 years of age.
- Referred to CR because of heart failure with reduced ejection fraction.
- Peripheral artery disease.
- Valve or pericardial surgery.
- Heart transplantation.
- Those unable to provide informed consent.
- Those unable to speak and read English.
- Night shift workers.
- Pregnant women.
- Those who will only attend full home-based CR.
Eligibility last updated 10/27.21. Questions regarding updates should be directed to the study team contact.