Search Results
MT2019-37: A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase III Trial of Alpha 1 - Antitrypsin (AAT) Combined with Corticosteroids vs Corticosteroids Alone for the Treatment of High Risk Acute Graft-versus-Host Disease (GVHD) Following Allogeneic Hematopoietic Stem Cell Transplant (CTN 1705)
This study is a phase III, multicenter, double-blinded, randomized, placebo-controlled trial designed to compare AAT and corticosteroids (CS) to placebo and CS as first line therapy for patients with high-risk acute GVHD. The primary objective of this trial is to compare the rate of complete response (CR) and partial response (PR) on Day 28 post-randomization between AAT and CS versus placebo to match (PTM) and CS in patients with high-risk acute GVHD.
• Patients 18 years of age or older
• Initial presentation of acute GVHD after allogeneic hematopoietic cell transplantation for any indication
• Any graft or donor source or conditioning intensity
• Clinical diagnosis of acute GVHD requiring systemic therapy with corticosteroids
• Prior exogenous AAT exposure for GVHD prophylaxis
• Relapsed, progressing, or persistent malignancy
• de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment
• Receiving other drugs for the treatment of GVHD
• Receiving systemic CS for any indication within 7 days before the onset of acute GVHD
Lifestyle Counseling and Medication for Adolescent Weight Management (QUEST)
This study will compare the effectiveness and durability of intensive behavioral counseling vs. medical management plus low-intensity behavioral counseling on BMI, body fat, cardiometabolic risk factors, and quality of life in adolescents with severe obesity. We hypothesize that liraglutide plus low-intensity behavioral counseling will elicit superior reductions in BMI (primary efficacy endpoint) and body fat and greater improvements in cardiometabolic risk factors and quality of life compared to intensive behavioral counseling at 56 weeks.
• Severe obesity (Body Mass Index (BMI) >/= 120% of the 95th percentile or BMI >/= 35 kg/m2)
• Age 12 to < 18 years old and Tanner stage >1
• Diabetes (type 1 or 2)
• Current or recent (< 6 months prior to enrollment) use of anti-obesity medication(s) defined as orlistat, phentermine, topiramate, combination phentermine/topiramate, liraglutide (or other GLP-1RA) and/or combination naltrexone/bupropion (monotherapy use of naltrexone or bupropion is not an exclusion)
• Previous bariatric surgery
• Any history of treatment with growth hormone
• Medically-documented history of bulimia nervosa
• Major psychiatric disorder as determined by the local medical monitor
• Unstable depression requiring hospitalization within the previous 6 month
• Any history of suicide attempt
• History of suicidal ideation or self-harm within the previous 30 days
• Current pregnancy or plans to become pregnant
• ALT or AST >/= 5 times the upper limit of normal
• Creatinine > 1.2 mg/dL
• Uncontrolled hypertension as determined by the local medical monitor
• Diagnosed and medically-documented monogenic obesity
• Medically-documented history of cholelithiasis
• Untreated thyroid disorder
• Medically documented history of pancreatitis
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
• Clinically significant heart disease as determined by the local medical monitor
• Personal history of malignant neoplasms within the past five years
• Hypersensitivity to any component of semaglutide
A Randomized Controlled Trial of Robotic versus Open Radical Hysterectomy for Cervical Cancer (ROCC trial)
This study is to investigate if robotic assisted laparoscopy (small incision surgery), is worse than open surgery (otherwise known as a laparotomy) when performing a radical hysterectomy for cervical cancer. Previous research has been done and shown that patients receiving laparoscopy had an increased risk of recurrence of their cervical cancer. But since that time a lot has been learned and improvements have been made, hence why we are relooking at the differences between the two surgical approaches.
Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1): Potential Use of Antioxidant/Anti-inflammatory Medications
The purpose of this study is to measure levels of blood and brain chemicals related to oxidative stress and inflammation in healthy volunteers and individuals with Type 1 Gaucher disease (GD1) to see if these levels are altered by GD1. We will also examine if there is a change in these blood and brain chemicals after participants begin taking oral N-acetylcysteine (NAC), which is available both as a prescription medication and a natural product that has antioxidant and anti-inflammatory effects.
• All participants must be 18 years or older.
• All participants must understand and cooperate with requirements of the study in the opinion of the investigators and must be able to provide written informed consent.
• Individuals with GD1 who are medically stable for participation in the study in the opinion of the investigator.
• GD1 patients must be on a stable, specific ERT and/or SRT therapy at a specific dose (e.g. on a units/kg basis) for at least 2 years.
• GD1 patients who have had a change in therapy, i.e. a change in dose or switch from one drug to another, can be enrolled after at least 6 months have elapsed since the change and is considered stable in the opinion of the clinician providing care to the patient.
• Healthy subjects who will be frequency-matched for age.
• All participants must not have taken antioxidants coenzyme Q-10, vitamin C, or vitamin E for 3 weeks prior to the study and during the course of the study.
• Medically unstable conditions in any group as determined by the investigators.
• Concurrent disease; medical condition; or an extenuating circumstance that, in the opinion of the investigator, might compromise subject safety, study compliance, completion of the study, or the integrity of the data collected for the study.
• Women who are pregnant or lactating or of child-bearing age who are not using acceptable forms of contraception.
• History of asthma that is presently being treated.
• Patients enrolled in another interventional study.
• Allergy to N-acetylcysteine.
• Patients who cannot or are unwilling to have blood drawn.
• Inability to undergo MRI scanning, including but not limited to: unable to remain still in an MRI scanner for more than 30 minutes, claustrophobia, presence of paramagnetic substances or pacemakers in body, weight over 300 lbs.
• Unable to adhere to study protocol for whatever reason.
Phase II trial of androgen deprivation therapy (ADT) and pembrolizumab for advanced stage androgen receptor-positive salivary gland carcinoma: Big Ten Cancer Research Consortium BTCRC-HN17-111
This is a Phase II multi-center, single-arm, non-blinded study combining androgen deprivation therapy (ADT) and pembrolizumab for patients with metastatic or locally recurrent androgen receptor-positive salivary gland carcinoma, not amenable to surgery or radiation. The primary objective is to determine the objective response rate (ORR) of pembrolizumab when given with goserelin in patients with locally recurrent or metastatic androgen receptor-positive salivary gland carcinoma not amenable to curative-intent treatment with surgery or radiation per RECIST 1.1.
• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Locally advanced, recurrent, or metastatic salivary gland carcinoma that is not amenable to curative surgery or radiation
• ECOG Performance Status of 0 or 1 within 28 days prior to registration.
• Local, pathologic testing of androgen receptor-positive salivary gland carcinoma will be performed as standard of care. Archival tissue must be available for central confirmation of androgen receptor-positive disease and for correlative studies. AR positivity will be defined according to IHC staining of tumor tissue with at least 20% of tumor staining positive with moderate intensity (1+ or greater).
• Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to registration.
• For patients who have been treated with prior therapy, patients must have documented progression of disease on their prior therapy for entry into the study.
• Patients with prior chemotherapy, radiation, or surgery as part of curative intent therapy are allowed. Any number of prior lines of systemic therapy is permitted for entry into this study so long as prior therapy did not include anti-androgen therapy or immune checkpoint blockade.
• If prior cancer treatment, the subject must have recovered from toxic effects of prior cancer treatment (other than alopecia) to ≤ Grade 1.
• Adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100,000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L
• Creatinine (Cr) OR Measured or calculated creatinine clearance (GFR can also be used in place of Cr or creatinine clearance) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) o International normalized ratio (INR) OR prothrombin time (PT) & aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• A male participant must agree to use contraception during the treatment period and for at least 8 months after the last dose of study treatment and refrain from donating sperm during this period.
• Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• Females of childbearing potential and males with partners of childbearing potential must be willing to abstain from heterosexual activity or to use a highly effect form of contraception from the time of informed consent until 8 months after treatment discontinuation.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
• Women of childbearing age with a positive serum pregnancy test within 72 hours prior to study registration.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
• Has received prior androgen deprivation therapy including orchiectomy, gonadotropin-releasing hormone (GnRH) agonists/antagonists, androgen receptor blocker, abiraterone, or enzalutamide.
• Has received prior systemic anti-cancer therapy including investigational agents within 14 days prior to registration.
• Has had an allogenic tissue or solid organ transplant.
• Has received prior palliative radiotherapy within 7 days of start of study treatment. Participants must have recovered from all radiation-related toxicities and require less than 10mg of prednisone (or equivalent corticosteroid) daily.
• Has received a live vaccine or live-attenuated vaccine within 28 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast ductal carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 14 days by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has ≥Grade 3 hypersensitivity to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has a known history of active TB (Bacillus Tuberculosis).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
COG APAL2020SC - Pediatric Acute Leukemia (PedAL) Screening Trial Developing New Therapies for Relapsed Leukemias
This study aims to use clinical and biological characteristics of acute leukemias to screen for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and blood from patients with leukemia that has come back after treatment or is difficult to treat may provide information about the patient's leukemia that is important when deciding how to best treat it, and may help doctors find better ways to diagnose and treat leukemia in children, adolescents, and young adults (0-<22 years old).
• Patients must be less than 22 years of age at the time of study enrollment
• Patient must have one of the following:
• Patient has known or suspected relapsed/refractory (including primary refractory) AML
• This includes isolated myeloid sarcoma
• Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome
• Patient has known or suspected relapsed ALL that meets one of the following criteria:
• Second or greater B-ALL medullary relapse, excluding KMT2Ar.
• Any first or greater B-ALL medullary relapse involving KMT2Ar.
• Any first or greater T-ALL medullary relapse with or without KMT2Ar.
• Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia
• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment related AML
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Circuit-Based Deep Brain Stimulation for Parkinsons disease; Udall Project 1 Aim 2 and 3
Study objectives: -To characterize spontaneous and movement-related LFP changes in STN and GP in externalized patients under conditions that modulates the severity of tremor, bradykinesia and rigidity (off meds/off stim; on meds/off stim; off meds/on stim, on meds/on stim). -To characterize and compare the relative effect of different forms of closed loop stimulation (e.g., triggered at specific thresholds of low beta/HFO PAC or beta band activity) to standard isochronal high frequency DBS on motor signs and performance during movement.
• Diagnosis of idiopathic PD
• A history of a good response to levodopa (carbidopa/levodopa) defined as at least a 30% improvement in motor UPDRS score
• DBS surgery or IPG battery replacement at UMN is planned as part of routine clinical care.
• Other significant neurological disorder
• History of dementia
• Prior history of stereotactic neurosurgery
• Patients with post-operative complications or adverse effects (e.g. ON stimulation dystonias) that affect patient safety or confound the experiment will be excluded from further study
• Pregnant women
Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
This partially randomized phase II/III trial studies how well cisplatin and combination chemotherapy works in treating children and young adults (≤ 30 years of age) with hepatoblastoma or liver cancer after surgery. Drugs used in chemotherapy, such as cisplatin, doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan, sorafenib, gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving combination chemotherapy after surgery may kill more tumor cells.
• Patients in Group F must have a body surface area (BSA) >= 0.6 m^2
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must be newly diagnosed with histologically-proven primary pediatric hepatic malignancies including hepatoblastoma or hepatocellular carcinoma, except as noted below; patients with a diagnosis of hepatocellular neoplasm, not otherwise specified, should be classified and treated per hepatoblastoma treatment arms; note that rapid central pathology review is required in some cases; please note: all patients with histology as assessed by the institutional pathologist consistent with pure small cell undifferentiated (SCU) HB will be required to have testing for INI1/SMARCB1 by immunohistochemistry (IHC) according to the practices at the institution
• Patients with histology consistent with pure SCU must have positive INI1/SMARCB1 staining
• For all Group A patients, WDF status as determined by rapid review will be used to further stratify patients to Group A1 or A2
• For Groups B, C and D, rapid review is required if patients are either >= 8 years of age or have an alphafetoprotein (AFP) =< 100 at diagnosis
• For all Groups E and F patients, rapid central pathology review is required
• In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy
• Clinical situations in which emergent treatment may be indicated include, but are not limited to, the following circumstances:
• Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)
• Uncorrectable coagulopathy
• For a patient to maintain eligibility for AHEP1531 when emergent treatment is given, the following must occur:
• The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility criteria at the time of emergent treatment
• Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP1531 enrollment
• Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
• Patients may have had surgical resection of the hepatic malignancy prior to enrollment; all other anti-cancer therapy for the current liver lesion is prohibited
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows:
• Age: maximum serum creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 06 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 5 x upper limit of normal (ULN) for age
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 10 x upper limit of normal (ULN) for age
• Shortening fraction of >= 28% by echocardiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment) or
• Ejection fraction of >= 47% by echocardiogram or radionuclide angiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment)
• Group F patients only: QT/corrected QT (QTc) interval =< 450 milliseconds for males and =< 470 milliseconds for females (assessed within 8 weeks prior to study enrollment)
• Normal pulmonary function tests (including diffusion capacity of the lung for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen) (for patients receiving chemotherapy [Groups A, B, C, D, E2, F]); for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser); therefore, patients with a pre-disposition syndrome who have a prior malignancy are not eligible
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving other anticancer agents
• Patients with uncontrolled infection
• Patients who previously received a solid organ transplant, other than those who previously received an orthotopic liver transplantation (OLT) as primary treatment of their hepatocellular carcinoma
• Patients with hypersensitivity to any drugs on their expected treatment arm
• Group C: Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
• Group D:
• Patients with chronic inflammatory bowel disease and/or bowel obstruction
• Patients with concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
• Group F:
• Patients with peripheral sensitive neuropathy with functional impairment
• Patients with a personal or family history of congenital long QT syndrome
• These criteria apply ONLY to patients who may receive chemotherapy (all groups other than Group E1):
• Female patients who are pregnant 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
• Note for Group F: patients of childbearing potential should use effective birth control during treatment with sorafenib and for at least 2 weeks after stopping treatment
GLNE 007 Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas
The purpose of this study if to determine if stool or blood can be used to detect colon cancers as early or earlier than colonoscopy. The researchers plan to use these samples to learn about specific proteins (also known as biomarkers) that may indicate colon polyps, colon cancer or an increased risk of developing colon cancer. In order to learn more about preventing and detecting colon and rectal cancer, we are collecting samples from subjects with cancer, adenomas, and colonoscopies who may be at risk for polyps.
• Willing to sign informed consent
• Able to physically tolerate removal of up to 60 ml of blood
• Adults at least 18 years old
• Willing to collect 1-2 stool samples and prepare a Fecal Immunochemical Test (FIT)
• Pregnant or nursing women who otherwise meet the eligibility criteria may participate
• Subjects with one of the following:
• Colorectal adenocarcinoma-not treated and in colon at time of stool collection (CRC bin)
• Adenoma-pathologically confirmed adenoma present in colon at time of stool collection (Adenoma Bin)
• Higher Risk Non-neoplastic Bin
• Subjects with a personal history of adenomas (confirmed by pathology) with none present on qualifying colonoscopy
• Subjects with a personal history of CRC (longer than 3 years ago because of exclusion criteria of cancer within last 3 years) with none present at time of qualifying colonoscopy
• Any family history of CRC (1st degree relative)
• Current positive screening stool test for blood, for DNA or for both within 12 months with no follow-up intervention.
• Average Risk, Non-neoplastic Bin
• No history or current finding of any colorectal neoplasia including CRC, adenomas, sessile serrated adenomas and no family history of CRC.
• Subjects who had CRC that was successfully treated at least three years ago may be considered eligible for the adenoma bin if their polyps are adenomas and there is no evidence of CRC, or for the higher risk non-neoplastic bin as noted above.
• Subjects whose screening colonoscopy shows any of these types of polyps may be included in the non-neoplastic or the higher risk non-neoplastic bin if they meet the other criteria noted above.
• Hyperplastic polyps
• Benign mucosal polyps
• Polypoid granulation tissue
• Prolapsed mucosal polyps
• Inflammatory polyp
• Transitional mucosal polyp
• Lipoma
• Gangleoneuroma
• Neuroma
• Hamartomatous polyp
• Cancer patients who have had any surgery, radiation, or chemotherapy for their current colorectal cancer prior to collecting the baseline samples
• History of or clinically active Inflammatory Bowel Disease
• Known HNPCC or FAP
• Inability to provide informed consent.
• Other active malignancy within 3 years of enrollment except any of the following:
• Squamous cell carcinoma of the skin
• Basal cell carcinoma of the skin
• Carcinoma in situ of the cervix, Stages Ia or Ib invasive squamous cell carcinoma of the cervix treated by surgery only. (Excluded if had pelvic radiation)
• Stage Ia Grade 1 adenocarcinoma of the endometrium treated with surgery
• Patients on active chemotherapy or radiation treatment for any purpose
• Known HIV or chronic active viral hepatitis
• Women who are pregnant
• CT colonography (virtual colonoscopy) patients
Efficacy of Belimumab and Rituximab Compared to Rituximab Alone for the Treatment of Primary Membranous Nephropathy (REBOOT)
This trial is a two-part study (Part A and Part B) of adults with primary membranous nephropathy, ages 18-75 inclusive. Part A is an open-label, PK phase to compare belimumab exposure between participants who have “low” proteinuria (≥ 4 to < 8 g/day) and “high” proteinuria (≥ 8 g/day) at Visit -1. Part B is a prospective, randomized, phase II, double-blind, placebo-controlled, multicenter clinical trial in adults with primary MN. Part B will commence after the analysis of the PK data in Part A.
• Diagnosis of one of the following:
• Primary membranous nephropathy (MN):
• Confirmed by kidney biopsy obtained in the past 5 years, or
• If relapsing following a complete remission or partial remission, confirmed with a kidney biopsy obtained in the past 7 years
• Nephrotic syndrome, and a contraindication to kidney biopsy (e.g., anti-coagulation, solitary kidney, body habitus that increases the risk of biopsy, or other contraindication in the opinion of the investigator).
• Serum anti-PLA2R positive;
• Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min/1.73m^2 while on maximally tolerated renin-angiotensin system (RAS) blockade;
• Proteinuria:
• ≥4 and < 8 g/day that has been present for ≥ 3 months while on while on maximally tolerated RAS blockade, or
• ≥8 g/day while on maximally tolerated RAS blockade.
• Blood pressure while on maximally tolerated RAS blockade:
• Systolic blood pressure ≤ 140 mmHg, and
• Diastolic blood pressure ≤ 90 mmHg
• Secondary cause of membranous nephropathy (MN) (e.g., systemic lupus erythematosus (SLE), drug, infection, malignancy) suggested by review of the subject's medical history and/or clinical presentation;
• Rituximab use within the previous 12 months;
• Rituximab use > 12 months ago:
• With an undetectable CD19 B cell count, or
• Did not result in a complete remission (CR) or partial remission (PR) with rituximab treatment alone (e.g., without other immunosuppressive or immunomodulatory therapy).
• Use of anti-B cell therapy other than rituximab within the previous 12 months (or 5 half-lives, whichever is greater);
• Cyclophosphamide use within the past 3 months;
• Use of other immunosuppressive medications, such as cyclosporine or tacrolimus, within the past 30 days;
• Use of systemic corticosteroids within the past 30 days;
• Use of any biologic investigational agent, defined as any drug not approved for sale in the country it is used, in the previous 12 months;
• Use of any non-biologic investigational agent in the past 30 days (or 5 half-lives, which ever is greater);
• Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥ 9.0%
• Patients with diabetic glomerulopathy on renal biopsy that is:
• Greater than Class I diabetic glomerulopathy, or
• Class I diabetic glomerulopathy with a history of poor diabetic control (e.g., HbA1c ≥ 9.0%) since time of biopsy;
• Unstable kidney function defined as > 15% decrease in the Estimated Glomerular Filtration Rate (eGFR) during the previous 3 months;
• Decrease in proteinuria by 50% or more during the previous 12 months;
• White blood cell (WBC) count < 3.0 x 10^3/µl;
• Absolute neutrophil count < 1.5 x 10^3/µl;
• Moderately severe anemia (hemoglobin <9mg/dL);
• History of primary immunodeficiency;
• Serum immunoglobulin A (IgA) < 10 mg/dL;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = ≥2 times the upper limit of normal (ULN);
• Positive human immunodeficiency virus (HIV) serology;
• Positive hepatitis C virus (HCV) serology, unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load 24 weeks after cessation of therapy);
• Evidence of current or prior infection with hepatitis B, as indicated by a positive HBsAg, positive HBcAb, or positive HBsAb serology without history of vaccination;
• Positive QuantiFERON - tuberculosis (TB) Gold test results, --Note: Tuberculin Purified Protein Derivative (PPD) test may be substituted for QuantiFERON - TB Gold test.
• History of lung disease with FVC < 70% predicted, DLCO < 70% predicted, or requiring supplemental oxygen;
• History of malignant neoplasm within the last 5 years, --Exception: basal cell or squamous cell carcinoma of the skin treated with local resection only, or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years.
• Absence of individualized, age-appropriate cancer screening;
• Women of child-bearing potential who are pregnant, nursing, or unwilling to be sexually inactive or use FDA-approved contraception until study week 104;
• Acute or chronic infection, including:
• current use of suppressive therapy for chronic infection,
• hospitalization for treatment of infection in the past 60 days, or
• parenteral anti-microbial (including anti-bacterial, anti-viral, or anti-fungal agents) use in the past 60 days for infection.
• History of anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies, including:
• rituximab, or
• belimumab.
• Evidence of serious suicide risk, including:
• any history of suicidal behavior in the last 6 months,
• any suicidal ideation in the last 2 months, or
• who, in the investigator's judgment, pose a significant suicide risk.
• Evidence of current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence in the past 12 months;
• Vaccination with a live vaccine within the past 30 days;
• Other diseases or conditions which, in the opinion of the investigator, would put the subject at risk or confound the results of the study; or
• Inability to comply with study and follow-up procedures.
Safety and Effectiveness of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood
This is an open-label, multi-center, single arm, Phase 1/2 study to evaluate the safety, PK, PD, and efficacy of quizartinib administered in combination with fludarabine and cytarabine (FLA) (Re-Induction Cycles 1 and 2) chemotherapy for re-induction, with optional consolidation chemotherapy, and as a single agent continuation therapy (after optional, but strongly encouraged, HSCT per standard of care), in pediatric relapsed/refractory AML subjects aged ≥1 month old to <18 years old (and young adults up to 21 years old) with FLT3-ITD mutations.
• Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with ≥5% blasts in bone marrow, with or without extramedullary disease
• Is in first relapse or refractory to first-line high-dose chemotherapy with no more than 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction - prior HSCT is permitted
• Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as defined in the protocol
• Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is signed
• Has protocol-defined adequate performance status score
• Has fully recovered from the acute clinically significant toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines
• Has protocol-defined adequate renal, hepatic and cardiac functions
• If of reproductive potential, is permanently sterile or agrees to use highly effective birth control upon enrollment, during the period of therapy, and for 6 months following the last dose of study drug or cytarabine, whichever is later
• If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
• Participant/legal representative is capable of understanding the investigational nature of the study, potential risks, and benefits, and the patient (and/or legal representative) signs a written assent/informed consent
• Meets protocol-specified guidelines before inclusion in the continuation therapy phase
• Has been diagnosed with isolated central nervous system relapse, certain kinds of leukemia, or with myeloid proliferations related to Down syndrome
• Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the protocol
• Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient must be off vasopressors and have negative blood cultures for at least 48 hours prior to the start of systematic protocol therapy.
• Has known active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)
• Has known history of human immunodeficiency virus (HIV)
• Has history of hypersensitivity to any of the study medications or their excipients
• Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or immunotherapy other than as specified in the protocol
• Has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/assent, study participation, follow up, or interpretation of study results
• Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)
• Is otherwise considered inappropriate for the study by the Investigator
Long-Chain Fatty Acid Oxidation Disorders In-Clinic Disease Monitoring Program
The Disease Monitoring Program (DMP) will collect information for up to 10 years from adult and pediatric participants with a confirmed diagnosis of Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) on any treatment. The main purpose of the DMP is to assess the long-term safety and effectiveness of Dojolvi® (triheptanoin) in participants with LC-FAOD, and to establish the natural history, progression, and burden of LC-FAOD to patients and caregivers. Participants will be able to be part of this study for up to 10 years.
• Confirmed diagnosis of any LC-FAOD sub-type. Diagnosis must be confirmed by results of acylcarnitine profiles, and/or mutation analysis obtained from medical records or equivalent documentation.
• Willing and able to comply with all study procedures.
• Willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures. For minors (<16 or<18 years of age, as defined by region) willing and able (if possible) to provide written assent and have a legally authorized representative willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures.
• Female of child-bearing potential who become pregnant during the study will be invited to remain in the study. Pregnant females with LC-FAOD will be informed of the study and invited to enroll.
• Pregnant females carrying affected fetus(es) with confirmed pre-natal diagnosis of LC-FAOD, will also be informed of the study and invited to enroll.
• Presence of a concurrent disease or condition that would interfere with study participation or affect patient's safety in the opinion of the Investigator.
• Presence or history of any condition that, in the view of the Investigator, places the patient at high risk of not completing the study or would affect the interpretation of study results.
MT-2018-20: COG AALL1631 - International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Testing Imatinib in Combination With Two Different Cytotoxic Chemotherapy Backbones
This randomized phase III trial studies how well imatinib mesylate and combination chemotherapy work in treating patients (> 1 year and < 21 years) with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia. Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving imatinib mesylate and combination chemotherapy may work better in treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia.
• Diagnostic samples will be collected and analyzed according to the procedures of the National front-line protocol
• Patients should be enrolled on National ALL protocol prior to enrollment on EsPhALL2017/COGAALL1631. Regardless of initial front-line protocol baseline diagnostic samples must be available to develop an MRD probe
• BCR-ABL1 fusion (Ph+): newly diagnosed ALL (B-ALL or T-ALL) or mixed phenotypic acute leukemia (MPAL meeting 2016 World Health Organization [WHO] definition) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-PCR
• ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions identified according to National/Center procedures of each participating country. ABL-class fusions are defined as those involving the following genes: ABL1, ABL2, CSF1R, PDGFRB, PDGFRA, LYN. Methods of detection include fluorescence in-situ hybridization (FISH, e.g. using break-apart or colocalization signals probes), multiplex or singleplex reverse-transcription polymerase chain reaction (RT-PCR), whole transcriptome or panel-based ribonucleic acid (RNA)-sequencing
• Regardless of initial front-line protocol, laboratory reports detailing evidence of BCR-ABL1 or ABL-class fusion must be available for the National Trial Unit
• Ph+ ALL patients must have previously started induction therapy, which includes vincristine, a corticosteroid, usually PEG-L-asparaginase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
• Ph+ ALL patients have not received more than 14 days of multiagent induction therapy beginning with the first dose of vincristine
• Ph+ ALL patients may have started imatinib prior to study entry but have not received more than 14 days of imatinib
• ABL-class fusion patients must have previously completed the 4 or 5 weeks of multiagent Induction chemotherapy
• ABL-class fusion patients may have started imatinib during Induction IA, at the same time of or after the first vincristine dose
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2
• Direct bilirubin =< 2.0 mg/dL
• Shortening fraction of >= 27% by echocardiogram
• Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
• Corrected QT interval, QTc < 480 msec
• Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis, before study enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or serum creatinine within normal limits based on age/gender, as follows:
• 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
• 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
• 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
• 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
• 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
• Known history of chronic myelogenous leukemia (CML)
• ALL developing after a previous cancer treated with cytotoxic chemotherapy
• Active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
• Down syndrome
• Pregnancy and breast feeding
• Female patients who are pregnant 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 treatment according to protocol
• Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block
• Prior treatment with dasatinib, or any TKI inhibitor other than imatinib
• All patients and/or their parents or legal guardians must sign a written informed consent
MT2019-07: LONG-TERM FOLLOW-UP PROTOCOL FOR SUBJECTS TREATED WITH GENE-MODIFIED T CELLS
This study is designed for the following purpose: - To assess the risk of delayed adverse events (AEs) following exposure to genemodified(GM) T cells - To monitor for long-term persistence of GM T cells, including analysis of vector integration sites, as appropriate. - To monitor for generation of replication competent retroviruses (RCR) - To assess long-term efficacy following treatment with GM T cells - Describe growth, developmental outcome, and sexual maturity status for subjects who were aged < 18 years at time of GM T cell treatment - To assess long term health-related quality of life following treatment with GM T cells
• Received at least one gene-modified (GM) T-cell infusion in a previous Celgene sponsored or Celgene alliance partner-sponsored study, and have discontinued, or completed the post-treatment follow-up period in the parent treatment protocol, as applicable.
• Must understand and voluntarily sign an Informed Consent Form/Informed Assent Form prior to any study-related assessments/procedures being conducted.
An Open-Label, Pilot Clinical Trial To Test The Safety And Feasibility Of Intestinal Microbiota Transplantation In Patients With Pulmonary Arterial Hypertension
This pilot clinical trial will evaluate the initial safety and feasibility of intestinal microbiota transplantation (IMT) in patients with pulmonary arterial hypertension (PAH). This trial will inform development of future trials in treatment of PAH. Active drug in capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors will be administered to patients with PAH. This study will also allow for limited evaluation of pharmacokinetics in terms of donor microbiota engraftment and pharmacodynamics in terms of potential mechanisms. It will also allow for limited evaluation of cardiac endurance and function prior to and after IMT.
• Diagnosis of pulmonary arterial hypertension (PAH)
• On stable treatment for PAH for one month prior to enrollment
• Able to swallow capsultes
• Able to provide blood sample and fecal sample
• Dysphagia to pills
• Clinically active inflammatory bowel disease
• Pregnancy or breastfeeding
• Life expectancy of <6 months
• Presence of ileostomy or colostomy
• Taking immunosuppressants (calcineurin inhibitors, prednisone greater than or equal to 20mg/day, methotrexate, azathioprine, immunosuppressive biologics, JAK inhibitors)
• Neurotropenia (an absolute neurotrophil count < 0.5 x 10^9 cells/L)
• History of solid organ or bone marrow transplant
• Anticipated recurrent antibiotic use (participants with frequent urinary tract infections or sinusitis)
• History of severe anaphylactic food allergy
• History of celiac disease
• History of receiving cancer chemotherapy, immunotherapy, or radiation
Measurement of Upper Aerodigestive Tract Pressures During Phonation
The purpose of this pilot research study is to test whether a tool called “High-Resolution Manometry” can diagnose laryngeal dystonia (also known as spasmodic dysphonia) and measure how well treatment works. High-Resolution Manometry measures pressures from a small catheter that is passed from your nose into your throat. We believe that pressures in the throat might be different for people with laryngeal dystonia than for people without laryngeal dystonia, or with other types of voice disorders. If we can diagnose laryngeal dystonia shortly after symptoms start, we can get patients the treatment they need sooner.
• Have experienced improvement in voice quality following injection of botulinum toxin into the thyroarytenoid complex
• Have received their most-recent injection within 6 months
• Age 18-80 years old
• Able to participate in informed consent
• Able to read and write in English Healthy Controls
• Age 18-80
• Have no known voice problem
• Have a VHI-10 score of 10 or below
• Able to participate in the informed consent process
• Able to read and write in English
• Diagnosis of vocal tremor, abductor laryngeal dystonia, any type of vocal fold lesion, or vocal fold paralysis
• Known swallowing disorder (oropharyngeal or esophageal), with the exception of transient post-botulinum toxin injection-induced dysphagia
• Pregnant
• Prisoner
• Allergy to topical anesthetic
• Cannot fast for 6 hours (4 hour fast prior to study, up to 2 hours to complete the study)
• Recent facial trauma
• Recent nasal, pharyngeal, laryngeal, or esophageal surgery
• Known nasal, pharyngeal, or esophageal obstruction Healthy Controls
• VHI-10 Score of 11 or above
• Report having a current voice or swallowing disorder
• Pregnant
• Prisoner
• Allergy to topical anesthetic
• Cannot fast for 6 hours (4 hour fast prior to study, up to 2 hours to complete the study)
• Recent facial trauma
• Recent nasal, pharyngeal, laryngeal, or esophageal surgery
• Known nasal, pharyngeal, or esophageal obstruction
Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that that has either come back (relapsed) or does not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means that tumor cells are missing the SMARCB1 and SMARCA4 genes, which is related to having more aggressive cancers that are harder to treat. Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
• Patients must be >= 12 months of age at the time of study enrollment. For part A, patients must be <18 years old at enrollment. For part B, there is no upper age limit
• The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients <18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion
• Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic tumor bi-allelic SMARCB1 (INI1) or SMARCA4 loss or mutation from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies:
• Renal medullary carcinoma
• Malignant rhabdoid tumor (extra-CNS)
• Atypical teratoid rhabdoid tumor (CNS)
• Poorly differentiated chordoma
• Epithelioid sarcoma
• Other SMARCB1 or SMARCA4 deficient tumors
• Note: Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
• Part A: Patients must have either measurable or evaluable disease Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or RANO criteria for CNS tumors
• Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of > 50). Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
• >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyel osuppressiveAnti-CancerAgents.pdf
• Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Autologous stem cell infusion including boost infusion: >= 30 days
• Cellular therapy: >= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• External radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have had prior TIGIT targeting therapy
• Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137)
• Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment
• Patients must not be receiving concomitant systemic steroid medications and > 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
• The use of physiologic doses of corticosteroids (5 mg/m^2/day up to 10 mg/day of prednisone equivalent) is acceptable
• The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
• The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable
• Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha [TNF-alpha] agents) must have concluded >= 14 days prior to study enrollment
• For patients with solid tumors without known bone marrow involvement
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (must be performed within 7 days prior to enrollment)
• For patients with solid tumors without known bone marrow involvement
• Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
• A creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):
• Age; Maximum Serum Creatinine (mg/dL)
• 1 to < 2 years; Male: 0.6; Female: 0.6
• 2 to < 6 years; Male: 0.8; Female: 0.8
• 6 to < 10 years; Male: 1; Female: 1
• 10 to < 13 years; Male: 1.2; Female: 1.2
• 13 to < 16 years; Male: 1.5; Female: 1.4
• >= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance >= 70 mL/min/1.73 m^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
• Patients with known Gilbert disease: Total bilirubin < 3 x ULN
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL (must be performed within 7 days prior to enrollment)
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] v5) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
• International normalized ratio (INR) =< 1.5 (must be performed within 7 days prior to enrollment)
• Serum amylase =< 1.5 x ULN (must be performed within 7 days prior to enrollment)
• Serum lipase =< 1.5 x ULN (must be performed within 7 days prior to enrollment)
• Grade 1 or lower calcium level
• Note: can have history of hypercalcemia as long as controlled and asymptomatic
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 5 months after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.
• It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 5 months after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later
• Concomitant medications:
• Corticosteroids:
• Patients must not be receiving concomitant systemic steroid medications and >= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
• The use of physiologic doses of corticosteroids (5 mg/m^2/day up to 10 mg/day of prednisone equivalent) is acceptable
• The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
• The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
• Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
• Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible
• Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible
• Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
• Patients who have undergone allogeneic bone marrow or stem cell transplant are not eligible
• Patients with known, untreated CNS metastases will be excluded with the following exceptions:
• Patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows no evidence for active disease in the CNS
• Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible
• Patients who have active immune deficiency are not eligible
• Patients who have known active tuberculosis are not eligible
• Hepatitis B or C infection:
• Patients < 18 years old at enrollment, who have known hepatitis B or C
• Patients >= 18 years old at enrollment with:
• Positive hepatitis B surface antigen (HBsAg), OR
• Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) >= 500 IU/mL, OR
• Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test
• Note: For adults (>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test
• Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible
• Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count >= 200/uL, and have an undetectable viral load
• Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible
• Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible
• Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted
• Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
MT2016-15 :Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies
• Karnofsky performance status of ≥70% or Lansky play score ≥ 70%
• A related haploidentical bone marrow donor with up to 2 or 3 HLA locus-mismatches
• The donor and recipient must be HLA identical for at least one haplotype (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1.
• Adequate liver and renal function
• Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 40%
• Diffusion capacity corrected (DLCOcorr) > 40% predicted, and absence of O2 requirements
• > 6 months after prior autologous transplant (if applicable)
• Agrees to use contraception during study treatment
• Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
• Patients who are HIV+ must have undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation
• < 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor
• Pregnancy or breastfeeding
• Current active and uncontrolled serious infection
• Acute leukemia in morphologic relapse/persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods).
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy.
• stable non-bulky disease is acceptable.
• Active central nervous system malignancy Criteria For Donor Selection:
• Donors must be HLA-haploidentical relatives of the patient, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1.
• Eligible donors (14-70 years old) include biological children, siblings or half siblings, or parents, able and willing to undergo bone marrow harvesting.
• For donors <18 years, the maximum recipient weight (actual body weight) should not exceed 1.25 times the donor weight (actual body weight)1 In addition, bone marrow product volume should be limited to 20 ml/kg donor weight for donors <18 years.
Low sulfur fecal transplant for ulcerative colitis
This study is a pilot randomized controlled clinical trial examining how fecal microbiota transplant (FMT) given by capsules can change the bacteria and inflammation in people with active ulcerative colitis (UC). We will look at global changes of bacterial composition while on FMT versus those not on FMT. We are examining some specific groups of bacteria that are related to sulfate reduction. Will will measure the changes of sulfate reducing bacteria over time and among those who get better and those who don't. Overall, we aim to determine if we can alter the microbiota in UC towards a healthy, more diverse microbiota resembling the donor using capsule FMT material.
• Able and willing to provide consent
• English speaking
• Diagnosis of ulcerative colitis based on typical clinical-histopathic diagnosis
• Diagnosis of ulcerative colitis > 3 months
• Active disease on endoscopy (endoscopic Mayo subscore ≥ 1)
• Evidence of inflammation extending beyond a minimum of 20cm
• Any ongoing ulcerative colitis therapy must be at stable doses for 4 weeks prior to study and remain stable over the course of the study
• Extensive bowel resection
• Presence of ileostomy or colostomy
• Suspicion of ischemic colitis, radiation colitis or microscopic colitis
• Diagnosis of Crohn's disease
• Diagnosis of per-anal fistula or abscess
• Adenomatous polyps that have not been removed
• Use of pre or probiotics within 30 days of randomization
• Pregnancy
• Severe food allergies
• End stage liver disease or cirrhosis
• An absolute neutrophil count < 500 cell/µL
• Life expectancy < 6 months
Hmong Microbiome ANd Gout, Obesity, Vitamin C
The objectives of this study include: 1. Quantify the impact of vitamin C on patient outcomes, including serum urate level, gout-related symptoms, and obesity (measured by BMI) in both healthy Hmong adults and in Hmong patients with hyperuricemia (HU) and/or gout 2. Identify associations between individuals’ taxonomic and functional patterns of gut microbiota and its impact on the serum urate lowering effect of vitamin C 3. Compare taxonomic and functional patterns of gut microbiota between people with HU and/or gout and people without HU and gout 4. Identify associations between individuals’ taxonomic and functional patterns of gut microbiota and self-reported acute gout trigger foods
• Self-identified Hmong persons whose both parents are Hmong, with and without hyperuricemia (serum urate (UA) ≥ 6.8 mg/dL ) and/or gout (defined by 2020 American College of Rheumatology Guideline for the Management of Gout) are eligible for the study.
• For those with gout, participants qualify if they have serum UA ≥ 6.8 mg/dL based on the baseline measurement or serum UA < 6.8 mg/dL based on the baseline measurement with at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness (acute gout flare) in their lifetime, (with or without urate-lowering therapy)
• Allergy or sensitivity to vitamin C
• Diagnosis/history of:
• Gastrointestinal surgery including colectomy, ileectomy, and gastrectomy
• Inflammatory bowel disease
• Auto-immune disease
• Type I diabetes mellitus
• Severe kidney disease (i.e., on dialysis)
• End-stage liver disease (i.e. cirrhosis)
• Glucose-6-phosphate dehydrogenase deficiency, (due to increased bleeding risk in those with G6PD deficiency when receiving vitamin C)
• Pregnant or breastfeeding persons
• Current use of:
• Antibiotics
• Probiotics supplement
• Ketogenic diet
Fecal Microbiota Transplant for Postoperative Crohn's Disease
People with Crohn's disease often need surgery. The gut bacteria of people with Crohn's is associated with Crohn's disease coming back after surgery. Fecal microbiota transplant (FMT) after surgery might be a way to prevent Crohn's disease from coming back after surgery. This study aims to determine if fecal microbiota transplant (FMT) taken by capsules results in the same amount of good bacteria in the guts as FMT by colonoscopy in people with Crohn's disease who have had surgery. Participants will be randomized to get FMT by capsules or colonoscopy. Colonoscopy with biopsies 8-weeks after the FMT will be used to assess the good bacteria in the gut.
• Able and willing to sign informed consent form
• Age 18 or older
• English speaking
• Established CD for at least 6-months based on typical clinical, endoscopic, and histopathic evidence.
• Prior ileocecal resection for CD
• Stable medications for 30 days
• Women of reproductive age: Agree to remain abstinent or use effective birth control
• Able and willing to comply with all study procedures
• Antibiotic therapy within 15 days
• Probiotic therapy within 15 days
• Adenomatous polyps that have not been removed
• Anticipated antibiotic use over the study period
• Subtotal or total colectomy
• Current ostomy (ileostomy or colonoscopy)
• Anticipated surgical procedure over study period
• Pregnancy
• Severe food allergy
• Diagnosis of end stage liver disease or cirrhosis
• Absolute neutrophil count < 500 cell / uL
• Life expectancy < 6 months
Theta Phase-specific TMS to Modulate Prefrontal Activity
Approach/avoidance behavior is a reliable marker of the emotional processes in the human brain. Although existing scientific studies found a correlation between the approach/avoidance behavior and ongoing theta activity (3-7 Hz) in the left dorsolateral prefrontal cortex, the causal evidence of the phase-dependent role and strength of association between the prefrontal theta oscillations and approach/avoidance behavior are still unclear. Here, we will monitor the theta activity in real-time non-invasively using electroencephalography and probe it with transcranial magnetic stimulation at the peak vs. trough phases. These data will provide novel, causal understanding of the mechanisms of emotional processing in human brain.
• Age between 18 and 65 years old.
• Confident level of English language.
• Chronic condition that requires pharmacological treatment over the course of study participation.
• Metallic or electric implant in the head, neck, or chest area or otherwise MRI-noncompatible implants.
• History or evidence of seizures, head injuries with loss of consciousness, chronic neurological or mental disorder.
• Pregnancy or breast-feeding.
• History or evidence of alcohol or drug addiction.
Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of Viralym-M;(ALVR105) for the Treatment of Patients With Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplant
The study hypothesis is that the administration of Viralym-M to patients with virus-associated HC will demonstrate superiority for the time to resolution of HC (as measured by resolution of macroscopic hematuria) compared to patients treated with placebo. The primary hypothesis will be tested in patients with BKV viruria to demonstrate superiority over placebo in this population (BK Intent-to-Treat [ITT] Population). A supplementary analysis will be conducted in all patients with any viral-associated HC (BKV, JCV, AdV, EBV, CMV, and/or HHV-6) in order to evaluate efficacy in this broader population (ITT Population). Further detail is provided in the statistical section below and will be described in the Statistical Analysis Plan (SAP).
• Male or female ≥1 year of age.
• Had an allogeneic hematopoietic cell transplant (HCT) performed ≥21 days and ≤1 year prior to randomization.
• Myeloid engraftment confirmed, defined as an absolute neutrophil count ≥500/mm³ for 3 consecutive laboratory values obtained on different days, and platelet count >10,000/mm³ at the time of randomization.
• Diagnosed with HC based on the following criteria (all 3 criteria must be met):
• Clinical signs and/or symptoms of cystitis.
• Grade ≥3 hematuria, defined as macroscopic hematuria with visible clots.
• Viruria with ≥1 target virus (ie, BKV, JCV, AdV, CMV, EBV, and/or HHV-6).
• At least 1 identified, suitably matched posoleucel (ALVR105) cell line for infusion is available. Key Exclusion Criteria Participants who meet any of the following criteria will be excluded from participation in the study:
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
• Therapy with antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies ≤28 days before randomization.
• Evidence of active Grade >2 acute graft versus host disease (GVHD).
• Uncontrolled or progressive bacterial or fungal infections.
• Uncontrolled or progressive viral infections not targeted by posoleucel (ALVR105).
• Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder.
• Known or presumed pneumonia secondary to any organism that is not considered to be well-controlled by antimicrobial therapy.
• Pregnant or lactating or planning to become pregnant. Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Long-term toxicities and quality of life of cancer survivors treated with immunotherapy
Immunotherapies, such as immune checkpoint inhibitors, have greatly improved survival for many cancers and are now approved for over half of all cancer patients. However, many patients receiving immunotherapy experience Grade 3 and 4 toxicities, termed immune-related adverse events (IRAEs) which cause frequent hospitalizations, emergency department visits, impaired health-related quality of life (QOL) and often discontinuation of therapy. While clinical trials of immunotherapeutic drugs have reported on IRAEs over short time-periods, the real-life and long-term frequencies of and experiences with IRAEs outside of clinical trials, and the general experience of taking immunotherapies long-term remain unknown. The goal of this protocol is to build a prospective cohort study of cancer survivors who receive immunotherapies.
Biologic Abatement and Capturing Kids Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK OFF JSpA) (BACK-OFF JSpA)
This study is enrolling participants who have been diagnosed with juvenile spondyloarthritis, are taking a tumor necrosis factor inhibitor (TNFi) and have reached a clinically inactive disease state for a minimum of six months. Researchers want to know if children who have maintained inactive disease for at least 6 months can maintain quiet disease without taking their medication as frequently or stop the TNFi therapy. Quiet disease means that disease related symptoms are not active or being experienced in the patient. Researchers also want to know the safest method to bring patients off medication. If a flare does occur during therapy reduction, researchers want to find out whether they can predict when a flare is most likely to happen, and how quickly an inactive disease state can be recaptured.
• Males or females age 8 to 21 years
• Juvenile SpA diagnosis (symptom onset before their 16th birthday): Pediatric Rheumatology International Trials Organization (PRINTO) revision of the The International League of Associations for Rheumatology (ILAR) criteria enthesitis/spondylitis-related Juvenile idiopathic arthritis (JIA)
• Peripheral arthritis and enthesitis, or
• Arthritis or enthesitis, plus ≥ 3 months of inflammatory back pain and sacroiliitis on imaging, or
• Arthritis or enthesitis plus 2 of the following: (1) sacroiliac joint tenderness; (2) inflammatory back pain; (3) presence of Human leukocyte antigen (HLA-B27) ; (4) acute (symptomatic) anterior uveitis; and (5) history of a SpA in a first-degree relative
• Currently taking one of the following TNFi therapies (Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab) at standard doses and dosing intervals
• Have reached a clinically inactive disease state for a minimum of six months, as determined by treating physician
• English speaking or Spanish speaking
• Interested and willing to de-escalate TNFi therapy
Assessing Movement Disorder Patients
Patients with movement disorders, for example Parkinson’s disease (PD), essential tremor (ET) and dystonia, will be assessed using appropriate clinical and (sensor) quantified measures in order to obtain quantitative and qualitative data that is not consistently obtained in clinical exams. This data will aid in assessing trends and outcomes in motor and non-motor signs, side effects and symptoms that correlate with deep brain stimulation (DBS) lead location, stimulation parameters, and other variables, for those that have received this treatment, in order to inform neurosurgical and neurological practices aimed at optimizing treatment and therapy for movement disorders. For those patients that have received DBS lead implant(s), this study will include the analysis of patient’s clinical and/or research-related intraoperative neurophysiological recordings collected during the microelectrode recording portion of the DBS lead implant surgery. Additionally, researchers may analyze trends and outcomes by gathering data from retrospective and prospective chart review.
• Diagnosis or suspected diagnosis of Parkinson's disease, Essential Tremor, or Dystonia
• Aged: 10+
• History of dementia
• Patients with post-operative complications or adverse effects that affect patient safety or confound the experiment will be excluded from further study.
• Pregnant women
• Lactating women
An Adaptive Algorithm-Based Approach to Treatment for Adolescent Depression
The purpose of the current study is to evaluate the effectiveness of two adaptive treatment strategies (ATSs) for adolescent depression. The ATSs include delivery of an evidence-based psychotherapy for adolescent depression (interpersonal psychotherapy, IPT-A), systematic symptom monitoring, and an empirically-derived algorithm that specifies whether, when, and how to augment IPT-A. Two hundred depressed adolescents (age 12-18) will be recruited to participate in a 16-week SMART conducted in an outpatient community mental health clinic. Adolescents will be randomized to the IPT-A ATS condition (N=134) or the community clinic’s usual care (UC) (N=66). The aims of this R01 are to (1) evaluate the effectiveness of the ATSs embedded in this trial, (2) evaluate adolescents’ interpersonal functioning as a treatment target of IPT-A, (3) evaluate moderators of initial treatment and treatment augmentation strategies, and (4) conduct a process evaluation to identify barriers and facilitators that influenced ATS implementation.
Transcatheter Replacement of Stenotic Aortic Valve through Implantation of ACURATE in Subjects InDicatEd for TAVR
Graded Motor Imagery for Women at Risk for Developing Type I CRPS following Distal Radius Fractures
Background: Distal radius fractures (DRF) account for nearly one-fifth of all fractures in older adults, and women experience them 5x as often as men. Most DRF occur with low impact injuries to the wrist with an outstretched hand, and are often managed via closed treatment and cast immobilization. Women sustaining a DRF are at risk for upper limb immobility, sensorimotor changes, edema and type I complex regional pain syndrome (CRPS). Since CRPS onset is likely influenced by alterations in the brain’s somatosensory region, a rehabilitation intervention, Graded Motor Imagery (GMI), aims to restore cortical representation, including sensory and motor function, of the affected limb. To date, there are no studies on the use of GMI in reducing risk of or preventing the onset of type I CRPS in women with DRF treated with cast immobilization. Due to a higher likelihood of women with this injury developing type I CRPS, it is important to early intervention is needed. Methods/Design: This article describes a six-week randomized comparative effectiveness trial, where the outcomes of a modified GMI program (mGMI) + standard of care (SOC) group (n=33) are compared to a SOC only control group (n=33). Immediately following cast immobilization, both groups participate in four 1-hour clinic-based sessions, and a home program for 10 minutes three times daily until cast removal. Blinded assessments occur within 1 week of cast immobilization (baseline), at three weeks post cast immbolization, cast removal, and at three months post cast removal. The primary outcomes are patient reported wrist/hand function and symptomology on the Patient Rated Wristand Hand Evaluation, McGill Pain Questionnaire, and Budapest CRPS Criteria. The secondary outcomes are grip strength, active range of motion as per goniometry, circumferential edema measurements, and joint position sense. Discussion: This study will investigate the early effects of mGMI + SOC hand therapy compared to SOC alone. We intend to investigate whether an intervention, specifically mGMI, used to treat preexisiting pain and motor dysfunction might also be used to mitigate these problems prior to their onset. If positive effects are observed, mGMI + SOC may be considered for incorporation into early rehabilitation program.
• Women 55 years or older who have received closed treatment of distal radius fractures
• Central nervous system disorders (e.g., Brain injury, Spinal Cord Injury, Parkinson's, Multiple Sclerosis)
• Surgical fixation of fracture
• Non english speaking
• Concomitant ipsilateral injuries (i..e., BBFF)
• Other injuries to the affected limb interfering with baseline affected limb function
• Cognitive disorders which would preclude from following the testing commands and home program participation
• Conditions of the contralateral upper limb which would result in painful and markedly limited active hand, wrist and forearm motion as this may impact the brain's ability to perceive safe and proficient movement during mirror therapy.
• Visual impairments resulting in the inability to participate in GMI components
HEALEY ALS Platform Trial
The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. The trial is designed as a perpetual platform trial. This means that there is a single Master Protocol dictating the conduct of the trial. The Master Protocol describes the overall framework of the platform trial, including the target population, inclusion and exclusion criteria, randomization scheme, study endpoints, schedule of assessments, trial design, the mechanism for adding and removing interventions, and the statistical methodology and recommended statistical methods for evaluating interventions. Interventions (i.e., investigational products) are tested in trial regimens. Each trial regimen is described in its own Regimen-Specific Appendix (RSA) to the Master Protocol. The RSA will describe the nature of the intervention and its mechanism of action (MoA) including the mode and frequency of administration, dosage, the specific target population (to be selected within the pre-defined subsets of the Master Protocol), additional enrollment criteria (if any), sample size, and other specific intervention-related information and assessments (safety or other assessments that may be in addition to those outlined in the Master Protocol).
• Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS defined by revised El Escorial criteria.
• Age 18 years or older.
• Capable of providing informed consent and complying with study procedures, in the SI's opinion.
• Time since onset of weakness due to ALS ≤ 36 months at the time of the Master Protocol Screening Visit.
• Vital Capacity ≥ 50% of predicted capacity for age, height, and sex at the time of the Master Protocol Screening Visit measured by Slow Vital Capacity (SVC), or, if required due to pandemic-related restrictions, Forced Vital Capacity (FVC).
• Participants must either not take riluzole or be on a stable dose of riluzole for ≥ 30 days prior to the Master Protocol Screening Visit. Riluzole-naïve participants are permitted in the study.
• Participants must either not take edaravone or have completed at least one cycle of edaravone prior to the Master Protocol Screening Visit. Edaravone-naïve participants are permitted in the study.
• Participants must have the ability to swallow pills and liquids at the time of the Master Protocol Screening Visit and, in the SI's opinion, have the ability to swallow for the duration of the study.
• Geographically accessible to the site.
• Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant, according to SI's judgment (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, or clinically significant laboratory abnormality or EKG changes). Lab abnormalities include, but are not limited to: Hemoglobin < 10 g/dL, White Blood Cells < 3.0 x 103/mm3, Neutrophils, Absolute ≤ 1000/mm3, Eosinophilia (absolute eosinophil count of ≥ 500 eosinophils per microliter), low platelet counts (< 150 x 109 per liter), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN), eGFR < 30 mL/min/1.73m2, thyroid-stimulating hormone (TSH) levels >10 mIU/L or <0.01 mIU/L.
• Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the SI's opinion.
• Active cancer or history of cancer, except for the following: basal cell carcinoma or successfully treated squamous cell carcinoma of the skin, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies curatively treated and with no evidence of disease recurrence for at least 3 years.
• Use of investigational treatments for ALS (off-label use or active participation in a clinical trial) within 5 half-lives (if known) or 30 days (whichever is longer) prior to the Master Protocol Screening Visit.
• Exposure at any time to any gene therapies under investigation for the treatment of ALS (off-label use or investigational).
• If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or of child-bearing potential and unwilling to use effective contraception for the duration of the trial and for 3 months, or longer as specified in each RSA, after discontinuing study treatment.
• If male of reproductive capacity, unwilling to use effective contraception for the duration of the trial and for 3 months, or longer as specified in each RSA, after discontinuing study treatment.
• Anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the SI's opinion.
• If a participant is being re-screened, the disqualifying condition has not been resolved, or the mandatory wash-out duration has not occurred.
• For those participating in the optional CSF collection, contraindication to undergoing a lumbar puncture (LP) in the SI's opinion. Participants undergoing the LP must not be currently taking anticoagulation medications such as warfarin that would be a contraindication to LP; aspirin and non-steroidal anti-inflammatories are allowed.