StudyFinder
Search Results Within Category "Brain & Neurology"
17 Study Matches
Project: Every Child for Younger Patients With Cancer (EVERYCHILD)
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Massey, Gita, V.
NCT02402244
HM20006485
Inclusion Criteria:
* Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
* Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
* Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
* All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of one "1" (borderline), two "2" (carcinoma in situ) or three "3" (malignant)
* All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
* All neoplastic lesions of the kidney regardless of behavior, i.e., benign, borderline or malignant
* The following other benign/borderline conditions:
* Mesoblastic nephroma
* Teratomas (mature and immature types)
* Myeloproliferative diseases including transient myeloproliferative disease
* Langerhans cell histiocytosis
* Lymphoproliferative diseases
* Desmoid tumors
* Gonadal stromal cell tumors
* Neuroendocrine tumors including pheochromocytoma
* Melanocytic tumors, except clearly benign nevi
* Ganglioneuromas
* Subjects must be =\< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network \[NCTN\]) therapeutic study, for which there is a higher upper age limit
* All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
* If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1 OTHER: Cytology Specimen Collection Procedure, OTHER: Medical Chart Review
Adrenal Gland Pheochromocytoma, Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Kidney Neoplasm, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Neoplasm, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neoplasm of Uncertain Malignant Potential, Neuroendocrine Neoplasm, Stromal Neoplasm
Safety and Tolerability of AZD1390 Given With Radiation Therapy in Patients with Brain Cancer
Hess, Alison - ahess2@vcu.edu
Chen, Zhi-Jian
NCT03423628
HM20012958
Modality: Chemotherapy (nos), Modality: Radiotherapy
Brain and Nervous System
Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Gowda, Madhu, S
NCT03126916
HM20015351
Inclusion Criteria:
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patient must be \>= 365 days and =\< 30 years of age at diagnosis
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:
* Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
* MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
* Age \> 547 days regardless of biologic features
* Patients with INRG stage MS disease with MYCN amplification
* Patients with INRG stage L2 disease with MYCN amplification
* Patients \> 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
* Patients \>= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/sex as follows:
* 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
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \> 50% by echocardiogram or radionuclide angiogram
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): See ANBL2131 (NCT06172296) protocol for eligible high-risk neuroblastoma diagnoses
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): In addition, all patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) Arm E must have tumors with an ALK aberration
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Given the lack of data with lorlatinib in infant populations, patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) must be \> 1 year of age at time of transfer to ANBL1531 (NCT03126916). Patients \< 1 year of age found to have a qualifying ALK alteration as part of ANBL2131 (NCT06172296) may continue to participate in ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients initially recognized to have high-risk disease must have received no more than one cycle of topotecan/cyclophosphamide either after enrollment to ANBL2131 (NCT06172296) or started emergently prior to enrollment to ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients may have received up to one cycle of intermediate risk chemotherapy prior to initial enrollment to ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients may have received localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): In order to facilitate patient transfer and ensure timely distribution of lorlatinib, there are no blood count requirements to meet at time of transfer from ANBL2131 (NCT06172296) to ANBL1531 ((NCT03126916) Arm E. Note the blood count criteria that must be met prior to start of Induction cycle 2 on Arm E. Lorlatinib therapy should start no sooner than day 1 of Induction cycle 2
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): No known irreversible grade 2 or greater atrioventricular (AV) block
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Due the potential psychiatric risks from lorlatinib, patients should not have a personal history of a serious psychiatric disorder requiring pharmacologic intervention or severe enough to be considered life-threatening
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution deems feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients with bone marrow failure syndromes
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: 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
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Lactating females who plan to breastfeed their infants
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have previously received treatment with lorlatinib or other ALK inhibitor
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have undergone treatment arm randomization callback or started induction cycle 2 on ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have an INRG Stage L2 tumor without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients with bone marrow failure syndromes
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): 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
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Lactating females who plan to breastfeed their infants
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Autologous Hematopoietic Stem Cell Transplantation, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Busulfan, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Dexrazoxane Hydrochloride, BIOLOGICAL: Dinutuximab, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography Test, DRUG: Etoposide Phosphate, RADIATION: External Beam Radiation Therapy, RADIATION: Iobenguane I-123, RADIATION: Iobenguane I-131, DRUG: Isotretinoin, DRUG: Lorlatinib, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan Hydrochloride, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Sargramostim, PROCEDURE: Therapeutic Conventional Surgery, DRUG: Thiotepa, DRUG: Topotecan Hydrochloride, DRUG: Vincristine Sulfate
Ganglioneuroblastoma, Ganglioneuroblastoma, Nodular, Neuroblastoma
Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) (BEAT-MS)
Vences, Karina - venceskm@vcu.edu
Oh, Unsong
NCT04047628
HM20017222
Inclusion Criteria:
• Age 18 to 55 years, inclusive, at the time of the screening Visit -2.
• Diagnosis of MS according to the 2017 McDonald Criteria139.
• EDSS ≤ 6.0 at the time of randomization (Day 0).
• T2 abnormalities on brain MRI that fulfill the 2017 McDonald MRI criteria for dissemination in space139. A detailed MRI report or MRI images must be available for review by the site neurology investigator.
• Highly active treatment-resistant relapsing MS, defined as ≥ 2 episodes of disease activity in the 36 months prior to the screening visit (Visit -2). The two disease activity episodes will be a clinical MS relapse or MRI evidence of MS disease activity and must meet all the criteria described below:
• At least one episode of disease activity must occur following ≥ 1 month of treatment with one of the following: (i) an oral DMT approved by the FDA for the treatment of relapsing MS, or (ii) a monoclonal antibody approved by the FDA for the treatment of relapsing MS, or (iii) rituximab. Qualifying DMTs include: dimethyl fumarate, diroximel fumarate, monomethyl fumarate, teriflunomide, cladribine, daclizumab, ponesimod, siponimod, ozanimod, fingolimod, rituximab, ocrelizumab, natalizumab, alemtuzumab, ublituximab, and ofatumumab, and
• At least one episode of disease activity must have occurred within the 12 months prior to the screening visit (Visit -2), and
• At least one episode of disease activity must be a clinical MS relapse (see item c.i. below). The other episode(s) must occur at least one month before or after the onset of the clinical MS relapse, and must be either another clinical MS relapse or MRI evidence of disease activity (see item c.ii. below): i. Clinical MS relapse must be confirmed by a neurologist's assessment and documented contemporaneously in the medical record. If the clinical MS relapse is not documented in the medical record, it must be approved by the study adjudication committee (see Section 3.5), and ii. MRI evidence of disease activity must include ≥ 1 unique active lesion on one or more brain or spinal cord MRIs. Detailed MRI reports or MRI images must be available for review by the site neurology investigator. A unique active lesion is defined as either of the following: 1\. A gadolinium-enhancing lesion, or 2. A new non-enhancing T2 lesion compared to a reference scan obtained not more than 36 months prior to the screening visit (Visit -2). 6\. Candidacy for treatment with at least one of the following high efficacy BAT DMTs: cladribine, natalizumab, alemtuzumab, ocrelizumab, ofatumumab, ublituximab and rituximab. Candidacy for treatment for each BAT DMT is defined as meeting all of the following:
• No prior disease activity episode, as defined in Inclusion Criterion #5, with the candidate BAT DMT, and
• No contraindication to the candidate BAT DMT, and
• No treatment with the candidate BAT DMT in the 12 months prior to screening. 7\. Completion of COVID-19 vaccination series, according to the current Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations, ≥ 14 days prior to randomization (Day 0). 8\. Positive for VZV antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least 4 weeks prior to randomization (Day 0). 9\. Insurance approval for MS treatment with at least one candidate BAT DMT (see Inclusion Criterion #6). 10\. Ability to comply with study procedures and provide informed consent, in the opinion of the investigator. 11\. Females of childbearing potential (defined in Section 5.4.3.1) and males with female partners of childbearing potential are required to adhere to the contraception provisions of Section 5.4.3.1. 12\. For participants who use medicinal or recreational marijuana, willingness to substitute MARINOL® if randomized to AHSCT (Section 5.4.2.6).
Exclusion Criteria:
• Diagnosis of primary progressive MS according to the 2017 McDonald criteria.
• History of neuromyelitis optica spectrum disorder or MOG antibody disease.
• Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or treatment of COVID-19 are not considered investigational.
• Either of the following within one month prior to randomization (Day 0):
• Onset of acute MS relapse, or
• Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or equivalent.
• Initiation of any BAT DMT (see Section 5.2.1) between Visit -2 and randomization (Day 0).
• Brain MRI or cerebrospinal fluid (CSF) examination indicating a diagnosis of progressive multifocal leukoencephalopathy (PML).
• History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
• Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis.
• History of sickle cell anemia or other hemoglobinopathy.
• Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.
• Presence or history of mild to severe cirrhosis.
• Hepatic disease with the presence of either of the following:
• Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin ≥ 3.0 times the ULN in the presence of Gilbert's syndrome, or
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.0 times the ULN.
• Positive COVID-19 PCR test, or alternative nucleic acid amplification test (NAAT) per institutional standards, within 14 days prior to randomization (Day 0).
• Evidence of HIV infection.
• Positive QuantiFERON - TB Gold,TB Gold Plus, or T-SPOT®.TB test results. PPD tuberculin test may be substituted for QuantiFERON - TB Gold, TB Gold Plus, or T-SPOT®.TB test.
• Active viral, bacterial, endoparasitic, or opportunistic infections.
• Active invasive fungal infection.
• Hospitalization for treatment of infections or parenteral (IV or IM) antibacterials, antivirals, antifungals, or antiparasitic agents within the 30 days prior to randomization (Day 0) unless clearance is obtained from an Infectious Disease specialist.
• Receipt of live or live-attenuated vaccines within 6 weeks of randomization (Day 0).
• Presence or history of clinically significant cardiac disease including: a. Arrhythmia requiring treatment with any antiarrhythmia therapy, with the exception of low dose beta blocker for intermittent premature ventricular contractions. b. Coronary artery disease with a documented diagnosis of either: i. Chronic exertional angina, or ii. Signs or symptoms of congestive heart failure. c. Evidence of heart valve disease, including any of the following: i. Moderate to severe valve stenosis or insufficiency, or ii. Symptomatic mitral valve prolapse, or iii. Presence of prosthetic mitral or aortic valve.
• Left ventricular ejection fraction (LVEF) \< 50%.
• Impaired renal function defined as eGFR \< 60 mL/min/1.73 m2, according to the CKD-EPI formula144.
• Forced expiratory volume in one second (FEV1) \< 70% predicted (no bronchodilator).
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) \< 70% predicted.
• Poorly controlled diabetes mellitus, defined as HbA1c \> 8%.
• History of malignancy, except adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix. Malignancies for which the participant is judged to be cured will be considered on an individual basis by the study adjudication committee (see Section 3.5).
• Presence or history of any moderate to severe rheumatologic autoimmune disease requiring treatment, including but not limited to the following: systemic lupus erythematous, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, polymyositis, dermatomyositis, mixed connective tissue disease, polymyalgia rheumatica, polychondritis, sarcoidosis, vasculitis syndromes, or unspecified collagen vascular disease.
• Presence of active peptic ulcer disease, defined as endoscopic or radiologic diagnosis of gastric or duodenal ulcer.
• Prior history of AHSCT.
• Prior history of solid organ transplantation.
• Positive pregnancy test or breastfeeding.
• Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
• Psychiatric illness, mental deficiency, or cognitive dysfunction severe enough to interfere with compliance or informed consent.
• History of hypersensitivity to rabbit or Escherichia coli-derived proteins.
• Any metallic material or electronic device in the body, or other condition that precludes the participant from undergoing MRI with gadolinium administration, as determined by the site radiologist.
• Presence or history of ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage.
• Presence or history of other neurological disorders, including but not limited to CNS or spinal cord tumor; metabolic or infectious cause of myelopathy; genetically-inherited progressive CNS disorder; CNS sarcoidosis; or systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments.
• Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality.
• Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.
PROCEDURE: Autologous Hematopoietic Stem Cell Transplantation, BIOLOGICAL: Best Available Therapy (BAT)
Relapsing Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
Treatment-Resistant Relapsing Multiple Sclerosis (MS), Autologous Hematopoietic Stem Cell Transplantation (AHSCT), Autologous Peripheral Blood Stem Cells (PBMCs) Graft, Best Available Therapy (BAT), Disease-Modifying Therapy (DMT), BAT DMT
Testing an Immunotherapy Anti-cancer Drug, Nivolumab, for Advanced Cancers in Patients With Autoimmune Disorders, AIM-NIVO (AIM-NIVO)
- CTOclinops@vcu.edu
Poklepovic, Andrew, S
NCT03816345
HM20022009
Inclusion Criteria:
* Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting, as well as the neoadjuvant or perioperative setting in which such treatment is considered standard of care or has been approved. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab or other PD1/PD-L1 inhibitors are FDA-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI)
* Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
* Patients enrolled on the study can receive Nivolumab with other FDA-approved combinations according to the FDA package insert, including, but not limited to ipilimumab, cabozantinib or chemotherapy
* Patients who have previously received other forms of immunotherapy (high-dose \[HD\] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
* Age \>= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \>= 60)
* Life expectancy of greater than 12 weeks
* Leukocytes \>= 1,000/mcL
* Absolute neutrophil count \>= 500/mcL
* Platelets \>= 50,000/mcL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN or =\< 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
* Creatinine ULN OR glomerular filtration rate (GFR) \>= 30 mL/min (if using the Cockcroft-Gault formula)
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
* If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception
* WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy), tubal ligation, or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
* These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days
* Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately. Patients can resume treatment upon termination of a pregnancy or the completion of a successful pregnancy
* Ability to understand and the willingness to sign a written informed consent document
* Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort (Please note: Patients with more than one autoimmune disease should receive assessments for all previously diagnosed autoimmune diseases. For example, a patient with psoriasis and IBD might be enrolled in the IBD cohort. Disease assessments for both psoriasis and IBD should be obtained, as per protocol. Case report forms \[CRFs\] for all relevant autoimmune diseases should be utilized. However, all additional cohort requirements will be considered optional and only the assessments from the assigned cohort will be considered mandatory)
* DM/SSc-SPECIFIC INCLUSION: Patients with known SSc or DM according to updated classification criteria (Van den Hoogan et al., Arthritis Rheum 2013;65(11):2737-47; Lundberg et al., A\&R in press). Overlap features are permitted, but patients must meet criteria for a "primary diagnosis" of DM or SSc
* DM/SSc-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for DM or SSc unless specifically excluded
* DM/SSc-SPECIFIC INCLUSION: Patients must have a baseline computed tomography (CT) of the chest (within 6 months of study entry)
* RA-SPECIFIC INCLUSION: Rheumatologist-diagnosed RA requiring prior treatment with disease-modifying antirheumatic drugs (DMARDs) before patient was diagnosed with current malignancy. We recommend, but do not require, documentation for meeting 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA
* RA-SPECIFIC INCLUSION: Prednisone up to 10 mg/day will be allowed. Intraarticular steroids will be allowed for the treatment of new symptomatic joints
* RA-SPECIFIC INCLUSION: Nonsteroidal anti-inflammatory drugs (NSAIDs) will be allowed
* SLE-SPECIFIC INCLUSION: SLE diagnosed by a rheumatologist. The patient should meet the revised 1997 American College of Rheumatology (ACR) classification criteria for SLE, but this is not mandatory
* ULCERATIVE COLITIS (UC)-SPECIFIC INCLUSION: Diagnosis of UC must be made by endoscopy with biopsies
* UC-SPECIFIC INCLUSION: Complete colonoscopy with biopsies during study screening, within 8 weeks before initial nivolumab administration, or within 4 weeks after initial nivolumab administration
* UC-SPECIFIC INCLUSION: Patients must test negative for hepatitis B (antigen \[Ag\] negative, antibody \[core (c)Ab\] negative, antibody \[surface (s)Ab\] positive or negative) and Mycobacterium tuberculosis (purified-protein- derivative \[PPD\] or enzyme-linked immunospot assay \[ELISpot or T-spot\]) or be on appropriate anti-microbial treatment for these infections
* UC-SPECIFIC INCLUSION: Mild Disease Cohort: Patients must be in clinical remission, defined as a Mayo Clinic score (MCS) of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 either without medications, or treated with 5-ASA derivative, probiotic, or prior fecal transplant
* UC-SPECIFIC INCLUSION: Moderate Disease Cohort: Patients must be in clinical remission, defined as a MCS of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 on 6-mercaptopurine, azathioprine, methotrexate, or rectal hydrocortisone, budesonide, or one of these medications in combination with any of the medications listed in the Mild cohort
* UC-SPECIFIC INCLUSION: Severe Disease Cohort (A or B): Patients must either be A) in clinical remission, defined as a MCS of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 on a biologic therapy targeting tumor necrosis alpha (TNF-α) (infliximab, adalimumab, golimumab, or other approved agent in this class), α4β7 integrin (vedolizumab or other approved agent in this class), selective JAK1 inhibitor (upadacitinib or other approved agent in this class), IL-23p19 inhibitors (risankizumab or other approved agent in this class), selective sphingosine 1-phosphate receptor (S1PR) inhibitors (ozanimod, etrasimod or other approved agent in this class), or one of these biologic therapies in combination with any of the medications listed in the Mild or Moderate cohort, or B) have mild active disease defined as a MCS of 3-5 and no subscore higher than 2, and an endoscopic subscore of \< 2 on one of the medications or combination of medications defined for the Moderate or Mild cohort
* CROHN'S DISEASE (CD)-SPECIFIC INCLUSION: Complete colonoscopy with biopsies during study screening, within 8 weeks before initial nivolumab administration, or within 4 weeks after initial nivolumab administration
* CD-SPECIFIC INCLUSION: If patients have prior known disease in the stomach or small intestines, appropriate endoscopic evaluation (esophagogastroduodenoscopy/video capsule endoscopy) and/or imaging (computed tomography or magnetic resonance enterography) must also be current within 4 weeks prior to nivolumab administration
* CD-SPECIFIC INCLUSION: Deep enteroscopy techniques, such as double balloon enteroscopy, will not be required
* CD-SPECIFIC INCLUSION: Patients must test negative for hepatitis B (sAg negative, cAb negative, sAb positive or negative) and M. tuberculosis (PPD or ELISpot or T-spot) or be on appropriate anti-microbial treatment for these infections
* CD-SPECIFIC INCLUSION: Mild Disease Cohort: Patients must be in clinical remission as defined by a Crohn's Disease Activity Index (CDAI) \< 150 either without treatment or on a 5-ASA derivative, probiotic, antibiotics, or following fecal transplant
* CD-SPECIFIC INCLUSION: Moderate Disease Cohort: Patients must be in clinical remission as defined by a CDAI \< 150 on 6-mercaptopurine, azathioprine, methotrexate, rectal hydrocortisone, budesonide, or one of these medications in combination with any of the medications listed in the Mild cohort
* CD-SPECIFIC INCLUSION: Severe Disease Cohort (A or B): Patients must either A) be in clinical remission as defined by a CDAI \< 150 on biologic therapy targeting TNF-α (infliximab, adalimumab, certolizumab pegol, or other approved agent in this class), IL-12/23p40 (Ustekinumab or other approved agent in this class), α4β7 integrin (vedolizumab or other approved agent in this class), selective JAK1 inhibitor (upadacitinib or other approved agent in this class), selective sphingosine 1-phosphate receptor (S1PR) inhibitors (ozanimod, etrasimod or other approved agent in this class), or one of these biologic therapies in combination with any of the medications listed in the Mild or Moderate cohort, or B) have mild active disease as defined by a CDAI of 150 to 220 on one of medications or combination of medications defined for the Moderate or Mild cohort
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For other autoimmune diseases that cannot be classified, the eligibility criteria will be determined by the managing rheumatologist or other autoimmune disease specialist, based on the clinical judgement and current American College of Radiology (ACR) classification guidelines or other relevant guidelines, as per the disease category in question
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For giant cell arteritis (GCA), patients must have had positive temporal artery biopsy for GCA and abnormal erythrocyte sedimentation rate (ESR) at time of diagnosis
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For polymyalgia rheumatica (PMR), patients must have clinical diagnosis in addition to elevated inflammatory markers including (ESR, C reactive protein \[CRP\])
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: Patients can be in remission (with no glucocorticoids or immunosuppressive medications) or have low-moderate activity, which is defined as being on prednisone ≤ 10 mg or equivalent
* MS-SPECIFIC INCLUSION: Patients must meet 2017 McDonald criteria for the diagnosis of MS (Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revision of the McDonald criteria. Lancet Neurol. 17(2):162-173.)
* MS-SPECIFIC INCLUSION: Patients with MS can be in remission and can have a history of being on immunomodulatory agents, but at the time of entry into the clinical trial, patients should be off any concurrent MS therapy for at least 2 weeks. Patients can resume concurrent MS therapy 2 weeks after Nivolumab initiation. Patients in the MS2 cohort may be receiving contemporary multiple sclerosis disease modifying therapies, including but not limited to anti CD20 agents (ocrelizumab, rituximab, ofatumumab, ublituximab), sphingosine 1 phosphate (S1P) modulators (fingolimod, siponimod, ozanimod, ponesimod), cladribine, or other FDA approved MS therapies
* MS-SPECIFIC INCLUSION: Patients must have neurologic stability for at least 4 weeks prior to nivolumab initiation
* SJS-SPECIFIC INCLUSION: SjS diagnosed by a rheumatologist or oral medicine provider. The patient should meet the American-European Consensus Criteria for Sjögren's Syndrome (Vitali, et al., 2002). If on treatment, the patient may only be on hydroxychloroquine and prednisone ≤ 10 mg or equivalent
* PSO/PSA-SPECIFIC INCLUSION: Patients with known PsO as diagnosed by a dermatologist or PsA by a rheumatologist and/or by Classification for Psoriatic Arthritis (CASPAR) criteria (Tillett et al., 2012)
* PSO/PSA-SPECIFIC INCLUSION: Patients must have stable disease as determined by the investigator with no change in systemic therapy and/or biologic therapy for at least 3 months, except for those on tumor necrosis factor (TNF) inhibitors. In the case of TNF inhibition, patients may have transitioned to an alternative biologic therapy with stable disease for at least 4 weeks. For PsA, no change in corticosteroid therapy for at least 1 month prior to baseline and dose must be 10 mg or less
* PSO/PSA-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for PsO or PsA unless specifically excluded
Exclusion Criteria:
* Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), if all of the following criteria are met:
* Repeat imaging demonstrates no new sites of bone metastases
* The lesion being considered for palliative radiation is not a target lesion
* Patients with prior therapy with an anti-PD-1 or anti-PD-L1
* Patients with prior allogeneic hematologic transplant
* Patients who are receiving any other anticancer investigational agents
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients with thymoma concurrent with myasthenia gravis
* UC-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment
* UC-SPECIFIC EXCLUSION: Prior colectomy
* UC-SPECIFIC EXCLUSION: Concurrent primary sclerosing cholangitis (PSC). Patients with PSC can be enrolled on the Other Autoimmune Diseases Cohorts
* UC-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup
* CD-SPECIFIC EXCLUSION: Known untreated abscesses, untreated and symptomatic strictures, short gut physiology, or isolated jejunal disease
* CD-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment
* CD-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup
* MS-SPECIFIC EXCLUSION: Patients with MS cannot have medical contraindications to gadolinium-enhanced magnetic resonance imaging (MRI) PROCEDURE: Biospecimen Collection, DRUG: Cabozantinib, DRUG: Fluoropyrimidine, BIOLOGICAL: Ipilimumab, BIOLOGICAL: Nivolumab, DRUG: Platinum Compound, DRUG: Platinum Doublet
Autoimmune Disease, Crohn Disease, Dermatomyositis, Hematopoietic and Lymphoid Cell Neoplasm, Inflammatory Bowel Disease, Malignant Solid Neoplasm, Multiple Sclerosis, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Sjogren Syndrome, Systemic Lupus Erythematosus, Systemic Scleroderma, Ulcerative Colitis
Longitudinal Cohort Registry of Cancer Survivors
Hong, Susan - susan.hong@vcuhealth.org
Hong, Susan
17880
HM20021510
Anus, Any Site, Bones and Joints, Breast, Brain and Nervous System, Other Hematopoietic, Other Female Genital, Other Endocrine System, Other Digestive Organ, Non-Hodgkin's Lymphoma, Myeloid and Monocytic Leukemia, Mycosis Fungoides, Multiple Myeloma, Melanoma, skin, Lymphoid Leukemia, Lung, Liver, Lip, Oral Cavity and Pharynx, Leukemia, other, Leukemia, Not Otherwise Specified, Larynx, Kidney, Kaposi's sarcoma, Ill-Defined Sites, Hodgkin's Lymphoma, Eye and Orbit, Esophagus, Corpus Uteri, Colon, Cervix, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Urinary, Urinary Bladder, Thyroid, Stomach, Soft Tissue, Small Intestine, Rectum, Prostate, Pancreas, Ovary, Other Skin
Anticoagulation in ICH Survivors for Stroke Prevention and Recovery (ASPIRE)
Kevin N Sheth, MD - kevin.sheth@yale.edu
NCT03907046
Inclusion Criteria:
* Age at least 18 years
* Intracerebral hemorrhage (ICH) (including primary intraventricular hemorrhage) confirmed by brain CT or MRI
* Can be randomized within 14-180 days after ICH onset
* Non-valvular AF (defined as atrial fibrillation or atrial flutter), documented by electrocardiography or a physician-confirmed history of prior AF
* Provision of signed and dated informed consent form by patient or legally authorized representative
* For females of reproductive potential: use of highly effective contraception
Exclusion Criteria:
* Index event is hemorrhagic transformation of a brain infarction or hemorrhage into a tumor
* History of earlier ICH within 12 months preceding index event
* Active infective endocarditis
* Clear indication for anticoagulant drugs (e.g., requires anticoagulation for deep vein thrombosis or pulmonary embolism) or antiplatelet drugs (e.g., requires aspirin or clopidogrel for recent coronary stent).
* Previous or planned left atrial appendage closure
* Clinically significant bleeding diathesis
* Serum creatinine ≥2.5 mg/dL
* Active hepatitis or hepatic insufficiency with Child-Pugh score B or C
* Anemia (hemoglobin \<8 g/dL) or thrombocytopenia (\<100 x 10\^9/L) that is chronic in the judgment of the investigator
* Pregnant or breastfeeding
* Known allergy to aspirin or apixaban
* Concomitant participation in a competing trial
* Considered by the investigator to have a condition that precludes safe or active participation in the trial
* Persistent, uncontrolled systolic blood pressure (≥180 mm Hg)
* ICH caused by an arteriovenous malformation (AVM) that has not yet been secured DRUG: Apixaban, DRUG: Aspirin
Intracerebral Hemorrhage, Atrial Fibrillation
Improving Traumatic Brain Injury Rehab Care With Comm Health Services: a Research Project Within the TBI Model System
Katherine Abbasi - katherine.walker@vcuhealth.org
NCT06188364
Inclusion Criteria:
* Participants must be adults (age 18 or older).
* Must be primary person responsible for supervision/care needs of person with TBI post-IRF discharge.
* The person with TBI must have been admitted to the Brain Injury Service Unit at SAI.
* If the care partner does not live in the same residence as the person with TBI, they must provide multiple daily check-ins on day-to-day care.
* Must agree to use mHealth (texts, calls) and possess or be eligible to acquire a smart phone.
Exclusion Criteria:
* Any severe cognitive impairment that precludes the ability to provide informed consent or safely function as the care partner for a vulnerable adult with TBI. OTHER: Standard of Care, OTHER: Experimental
Traumatic Brain Injury
Community Health Services, Rehabilitation Care Transitions, Caregiver Supports
Parkinson's Foundation PD GENEration Genetic Registry
Kamalini Ghosh, MS - kghosh@parkinson.org
NCT04994015
Inclusion Criteria:
* Study Population 1: PWP (open for recruitment)
• Meet Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's Disease: probable diagnosis.
• Willingness to undergo genetic testing, and choose to be informed of genetic testing results for GBA, LRRK2 and 5 additional PD related genes (SNCA, VPS35, PRKN, PINK-1, PARK7).
• Capacity to give full informed consent in writing or electronically, and have read and signed the informed consent forms (ICFs) based on site clinician's determination.
• Able to perform study activities (including completion of either online, in-person or paper surveys). Study Population 2: People at risk of developing PD (not open for recruitment) 1\. Family members of Study Population 1 may be invited to participate in the study if confirmatory genetic testing is deemed necessary by the genetic testing laboratory.
Exclusion Criteria:
• Diagnosis of an atypical parkinsonian disorder (i.e., multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies, corticobasal syndrome), including that due to medications, metabolic disorders, encephalitis, cerebrovascular disease, or normal pressure hydrocephalus.
• Individuals who have received a blood transfusion within the past 3 months.
• Individuals who have active hematologic malignancies such as lymphoma or leukemia.
• Individuals who have had a bone marrow transplant within the past 5 years.
• Under the age of 18
DEVICE: Lab Assay for seven genetic variants for Parkinson's Disease
Parkinson's Disease
Genetics, Genetic Counseling, Whole Genome Sequencing
Randomized Controlled Trial of Treatment to Optimize Heart Rate Variability for Persistent Post-Concussion Symptoms
Brett Brooks - bret.brooks@vcuhealth.org
NCT07071350
Inclusion Criteria:
* age 18 or older
* History of military service
* Self-Reported hx of 1 or more mild TBI
* Most recent TBI more than 1 year ago
* Significant Persistent Post-Concussion Symptom burden (Neurobehavioral Symptom Inventory \[NSI\] total score greater than or equal to 20).
* Current Sleep Difficulties
* Fluent English
* Able to provide Informed Consent
Exclusion Criteria:
* Any TBI with severity greater than mild (i.e., Moderate or Severe TBI defined as initial injury loss of consciousness (LOC) duration \>30 minutes, posttraumatic amnesia (PTA) duration \>24 hours, or traumatic hemorrhage on head computerized tomography (CT) and determined by the study investigator based on information gathered during administration of the study's validated TBI structured interview instrument.
* Conditions or medications that can affect HRV measurement (pacemaker or an implant that stimulates your heart (e.g., cardioverter-defibrillator or ICD); heart transplant or heart surgery within the last year, including bypass or other surgery, but not including a stent)
* Hx of stroke
* Mental conditions that may impede adherence (e.g., dementia, psychotic disorder, panic disorder) OTHER: HRV Coherence Ratio, BEHAVIORAL: NSI, BEHAVIORAL: Pittsburgh Sleep Quality Index (PSQI), BEHAVIORAL: Quantitative Sleep Measures, BEHAVIORAL: Patient Global Impression of Change (PGIC), BEHAVIORAL: Cognitive Performance/NIH Toolbox Cognitive Battery, OTHER: Pain Interference/TBI-QoL Pain Interference Short-Form, BEHAVIORAL: Patient Health Questionnaire-9 (PHQ-9), BEHAVIORAL: PTSD Checklist for DSM-5 (PCL-5), OTHER: HRV Biofeedback (HRV-B), OTHER: Psychoeducational (Edu) Comparator Intervention
Autonomic Nervous System Disease, Concussive Injury, Mild Traumatic Brain Injury, Post Traumatic Stress Disorder, Persistent Post Concussion Syndrome
Naxitamab Added to Induction for Newly Diagnosed High-Risk Neuroblastoma
BCC Enroll - BCCEnroll@pennstatehealth.psu.edu
NCT05489887
Inclusion Criteria:
• Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:
• Subjects with newly diagnosed neuroblastoma with INRGSS Stage M disease with either of the following features:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
• 365 days to ≥ 547 days of age without MYCN amplification, but unfavorable biologic features such as unfavorable histology (INPC) or diploid tumor (DNA index=1) or the presence of any segmental chromosome aberration (SCA) (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q); OR
• Age \> 547 days of age regardless of biologic features Subjects with newly diagnosed neuroblastoma with INRGSS Stage MS disease with either of the following:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals); OR
• 365 days to ≥ 547 days (18 months) of age without MYCN amplification, but unfavorable biologic features such as unfavorable histology (INPC) or diploid tumor (DNA index=1) or SCA as above Subjects with newly diagnosed neuroblastoma INRGSS Stage L2 disease with either of the following:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals); OR
• 18 months to \<5 years of age without MYCN amplification, but with unfavorable histology (INPC); OR
• ≥5 years of age without MYCN amplification, but with undifferentiated or poorly differentiated INPC Subjects with newly diagnosed neuroblastoma INRGSS Stage L1 disease that is incompletely resected with MYCN amplification. Subjects \> 547 days of age initially diagnosed with INRGSS Stage L1, L2 or MS disease who progressed to Stage M without prior chemotherapy may enroll within 4 weeks of progression to Stage M. Subjects ≥ 365 days of age initially diagnosed with MYCN amplified INRGSS Stage L1 disease who progress to Stage M without systemic therapy may enroll within 4 weeks of progression to Stage M.
• Subjects must be age ≤ 21 years at initial diagnosis.
• Subjects must be \>12 months of age at enrollment.
• Adequate cardiac function defined as:
• Shortening fraction of ≥ 27% by echocardiogram, or
• Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.
• Adequate liver function must be demonstrated, defined as:
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
• ALT (SGPT) \< 5 x upper limit of normal (ULN) for age
• 1\. Subjects must have adequate renal function defined as: * For subjects \< 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr * For subjects ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr) * OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
• A negative serum pregnancy test is required for subjects of childbearing potential (≥13 years of age or after onset of menses)
• Both male and female post-pubertal study subjects must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of \<1% per year when used consistently and correctly) from the time of informed consent (and assent, as applicable) until 6 months after study treatment discontinuation. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence.
• Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines and applicable local regulations.
Exclusion Criteria:
• Subjects who are less than 1 year of age
• Subjects who are 12-18 months of age with INRGSS Stage M and all stage L2 subjects with favorable biologic features (i.e., nonamplified MYCN, favorable pathology, and DNA index \> 1) are not eligible.
• Subjects who have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy.
• Treatment with immunosuppressive treatment (topical, inhaled and short-term emergency steroids excluded) within 4 weeks prior to enrollment
• Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry \< 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
• Subjects receiving any investigational drug concurrently.
• Subjects with any other medical condition, including but not limited to malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study
• Subjects with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of investigational medicinal products (IMPs) or to significantly increase the severity of the toxicities experienced from trial treatment.
DRUG: Naxitamab
Neuroblastoma
naxitimab, induction
Strategy for Improving Stroke Treatment Response (SISTER)
Rebeca Aragon Garcia, BS, CCRC - aragonra@ucmail.uc.edu
NCT05948566
Inclusion Criteria:
• Age 18 years and older
• Suspected anterior circulation acute ischemic stroke
• NIH Stroke Scale score ≥4 prior to randomization a. The participant must have a clearly disabling deficit if NIHSS is 4-5.
• Favorable baseline neuroimaging consisting of all of the following:
• ASPECTS of 6 or more on CT (or ASPECTS of ≥7 on MRI)
• Favorable perfusion imaging on CT perfusion (CTP)/MR-perfusion weighted imaging (PWI) consisting of all of the following: i. Mismatch ratio of penumbra: core \>1.2 ii. Mismatch volume \>10 cc iii. Core \<70 cc c. If CT hypodensity is present, then in the investigator's visual assessment, the total acute infarct volume combined area of (a) the CT hypodensity and (b) the perfusion-based core volume (CBF\<30%) should be smaller than perfusion-based volume (area of Tmax\>6s minus CBF\<30%).
• Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well.
• Able to receive assigned study drug within 120 minutes of qualifying perfusion imaging. \*
• Informed consent for the study participation obtained from participant or their legally authorized representatives. * Study drug administration is encouraged within 90 minutes after qualifying perfusion image but is allowed up to 120 minutes. After 120 minutes, another perfusion image to ensure that inclusion criteria are met is required.
Exclusion Criteria:
• Received endovascular treatment with clot engagement.
• Patients who undergo groin puncture but clot engagement is not attempted due to spontaneous distal migration are permitted to be enrolled in the trial if all other eligibility criteria are met.
• Patients who undergo groin puncture but clot is not engaged due to reasons other than spontaneous distal migration are NOT permitted.
• Received or planned to receive intravenous thrombolysis.
• Pre-stroke modified Rankin score \>2.
• Previous treatment with TS23 or known previous allergy to antibody therapy.
• Known pregnancy, women who are breastfeeding or plan to breastfeed within 3 months of receiving TS23 or have a positive urine or serum pregnancy test for women of childbearing potential.
• Known previous stroke in the past 90 days.
• Known previous intracranial hemorrhage, intracranial neoplasm, subarachnoid hemorrhage, or arterial venous malformation.
• Known active diagnosis of intracranial neoplasm.
• Clinical presentation suggestive of a subarachnoid hemorrhage, even if initial CT scan was normal.
• Surgery or biopsy of parenchymal organ in the past 30 days.
• Known trauma with internal injuries or persistent ulcerative wounds in the past 30 days.
• Severe head trauma in the past 90 days.
• Persistent systolic blood pressure \>180mmHg or diastolic blood pressure \>105mmHg despite best medical management.
• Serious systemic hemorrhage in the past 30 days.
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with International Normalized Ratio (INR) \>1.7.
• Platelets \<100,000/mm3.
• Hematocrit \<25 %.
• Elevated aPTT above laboratory upper limit of normal.
• Creatinine \> 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine.
• Received the following within the previous 24 hours:
• If patient received unfractionated heparin within the last 24 hours, the patient must have an aPTT within normal range prior to enrollment.
• Low molecular weight heparins such as Dalteparin, enoxaparin, tinzaparin in full dose within the previous 24 hours.
• Received Factor Xa inhibitors (such as Fondaparinux, apixaban or rivaroxaban) within the past 48 hours.
• Received direct thrombin inhibitors (e.g., argatroban, dabigatran, bivalirudin, desirudin, lepirudin) within 48 hours.
• Received glycoprotein IIb/IIIa inhibitors within the past 14 days.
• Known pre-existing neurological or psychiatric disease which would confound the neurological/functional evaluations.
• Current participation in another research drug treatment protocol (i.e., participants could not start another experimental agent until after 90 days).
• Concurrent acute myocardial infarction, pulmonary embolism, deep venous thrombosis or other thrombotic event that requires anticoagulation or anti-platelet treatment.
BIOLOGICAL: TS23
Ischemic Stroke
C-SMART vs BE Well for Patients With Brain Tumors
Sarah Braun, Ph.D - sarah.braun@vcuhealth.org
NCT07224503
Patient
Inclusion Criteria:
* Patient of Virginia Commonwealth University Neuro-Oncology clinic
* Confirmed primary brain tumor diagnosis by histology or neuro-oncologist review of imaging
* At least one domain of neurocognitive function \>1.5 SD below the average or the individual's estimated premorbid functioning, using the expanded International Cognition and Cancer Task Force (ICCTF) clinical trials battery and Test of Premorbid Functioning (TOPF)62 for comparison; (3) \>1 month post brain surgery and/or radiation therapy, if applicable;
* Estimated premorbid intelligence using TOPF \>75.
* Patients must be age 18+ and
* Primarily English speaking.
Patient Exclusion Criteria:
* Presence of major neurocognitive impairment that would prevent participation in the intervention, and/or severe aphasia, and/or inability to understand and provide informed consent
* Referred participants who are suspected to have major neurocognitive impairment will be administered the Telephone Interview for Cognitive Status (TICS) during the pre-screening phase. Scores of \<20 indicate major neurocognitive impairment and will result in exclusion from study participation;
* Inability to attend weekly telehealth appointments
* Clinically significant insomnia symptoms coupled with report that insomnia is more interfering than cognitive symptoms
* \< 1 month post brain surgery and/or radiation therapy
* Unstable internet connection or an inability to work teleconferencing software. Participants will be supplied an iPad if they do not have an adequate device.
* Exclusion criteria for the MRI portion of the study includes (6)implants, objects, or devices that are not MR safe, as the MRI scan could cause them harm.
* Additionally, if female of childbearing years, they cannot be pregnant as the MRI scan may pose risk to the unborn fetus. Those participants who have implants, objects, or devices that are not MRI safe and/or are pregnant but are otherwise eligible will participate in all other study activities, excluding MRI.
Caregiver Inclusion Criteria
* Must enroll with a patient (see criteria above)
* Must be age 18+ and
* Primarily English speaking
Caregiver Exclusion Criteria
-N/A BEHAVIORAL: C-SMART, BEHAVIORAL: BE Well
Brain Tumor
Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial - Part 2 (FASTEST Part 2)
Joseph P Broderick, MD - broderjp@ucmail.uc.edu
NCT07227246
Inclusion Criteria:
• Patients aged 18-80 years, inclusive
• Patients with spontaneous ICH
• Able to treat with study medication (rFVIIa/placebo) within 120 minutes of stroke onset or last known well with a positive spot sign on pretreatment CT angiography or treatment within 90 minutes with or without spot sign.
• Efforts to obtain informed consent per EFIC guidelines (U.S.) or adherence to country-specific emergency research informed consent regulations (Canada, Germany, Spain, Finland, U.K., Japan, Australia)
Exclusion Criteria:
• Score of 3 to 7 on the Glasgow Coma Scale
• Secondary ICH related to known causes (e.g., trauma, aneurysm, arteriovenous malformation (AVM), oral anticoagulant use (vitamin K antagonists or novel oral anticoagulants) within the past 7 days, coagulopathy, etc.)
• ICH volume \< 2 cc or ≥ 60 cc
• Blood filling 2/3 or more of one lateral ventricle of the brain, OR, blood filling at least 1/3 of both lateral ventricles.
• Pre-existing disability (mRS \> 2)
• Symptomatic thrombotic or vaso-occlusive disease in past 90 days (e.g., cerebral infarction, myocardial infarction, pulmonary embolus, deep vein thrombosis, or unstable angina)
• Clinical or EKG evidence of ST elevation consistent with acute myocardial ischemia
• Brainstem location of hemorrhage (patients with cerebellar hemorrhage may be enrolled)
• Refusal to participate in study by patient, legal representative, or family member
• Known or suspected thrombocytopenia (unless current platelet count documented above 50,000/μL)
• Unfractionated heparin use with abnormal PTT
• Pro-coagulant drugs within 24 hours prior to patient enrollment into the FASTEST trial (example, tranexamic acid or aminocaproic acid)
• Low-molecular weight heparin use within the previous 24 hours
• Recent (within 90 days) carotid endarterectomy or coronary or cerebrovascular angioplasty or stenting
• Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered
• Recent (within 30 days) participation in any investigational drug or device trial or earlier participation in any investigational drug or device trial for which the duration of effect is expected to persist until to the time of FASTEST enrollment
• Planned withdrawal of care or comfort care measures
• Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency, or psychological disorder)
• Known or suspected allergy to trial medication(s), excipients, or related products
• Contraindications to study medication
• Previous participation in this trial (previously randomized)
• Females of childbearing potential who are known to be pregnant or within 12 weeks post-partum and/or lactating at time of enrollment -
BIOLOGICAL: Recombinant Factor VIIa, BIOLOGICAL: Biological/Vaccine: Placebo
Intracerebral Hemorrhage
Intracerebral hemorrhage, recombinant factor VIIa
Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors
BCC Enroll - BCCEnroll@pennstatehealth.psu.edu
NCT06541262
Inclusion Criteria:
• Age: Less than 30 years old at initial diagnosis
• Pathology All subjects must have a confirmed diagnosis of tumor type. Phase I: Relapsed/refractory solid tumors: Neuroblastoma, Ewing Sarcoma, Osteosarcoma, Rhabdomyosarcoma, Liposarcoma Phase II: * Relapsed/refractory Neuroblastoma * Relapsed/refractory Ewing sarcoma
• Tumor assessment: Disease assessment is required for eligibility and must be done after last dose of previous therapy and prior to first dose of study drug.
• Disease Status: Relapsed/Refractory Neuroblastoma Relapsed disease defined as neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol) and has now relapsed and is in any number of relapses. Refractory disease defined as High-risk neuroblastoma (as defined by INRG) that failed to achieve CR after at least 4 cycles of aggressive multi-drug induction chemotherapy, progression during upfront therapy or with disease remaining after standard immunotherapy. International Neuroblastoma Risk Group Staging System (INRG) High Risk NB defined as one of the following:
• Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M with MYCN amplification
• Age ≥ 547 days and INRG Stage M regardless of biologic features
• Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to Stage M without systemic chemotherapy
• Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to Stage M without systemic chemotherapy Relapsed/refractory Sarcoma Subjects that have relapsed following standard of care therapy or having progressed during standard of care therapy. Standard of care therapy for sarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy.
• Measurable or evaluable disease, including at least one of the following: * Measurable tumor by CT or MRI * MIBG or PET that is positive for disease * Bone Marrow biopsy/aspirate that is positive for disease
• Timing from prior therapy: Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer therapy and be within the following timelines:
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study.
• Small Molecule Inhibitors (anti-neoplastic agent): At least 2 weeks from the completion of therapy with a small molecule inhibitor.
• Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells, anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.).
• Radiotherapy: At least 30 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
• Stem Cell Transplant: * Allogeneic: No evidence of active graft vs. host disease * Allogeneic/Autologous: ≥ 2 months must have elapsed since transplant.
• MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.
• Subjects must have a Lansky or Karnofsky Performance Scale score of \>/= 50.
• Subjects must have adequate organ function at the time of enrollment: * Cardiac: Subjects must have a QTcF ≤ 480 msc. * Hematological: Hematological recovery as defined by ANC ≥750/μL * Liver: Adequate liver function as defined by AST and ALT \<5x upper limit of normal * Renal: Subjects must have adequate renal function defined as: * estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (for subjects \< 17 years old) (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr * estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (for subjects ≥17 years old (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr) * OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
• Subjects of childbearing potential must have a negative serum pregnancy test. Subjects of childbearing potential must agree to use effective measures to avoid pregnancy.
• Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).
Exclusion Criteria:
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the hematological and bone marrow suppression effects of prior therapy.
• Subjects who are currently receiving Vitamin K antagonists (warfarin).
• Subjects who are currently receiving the class of lipid-lowering medications HMG-CoA reductase inhibitors (statins).
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
• Subjects with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the subject's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.
• Subjects with any of the following gastrointestinal disorders:
• Active malabsorption (e.g. short gut) syndrome.
• Uncontrolled diarrhea (excess of 4 stools/day)
• Gastritis, ulcerative colitis, Chron's disease or hemorrhagic coloproctitis
• History of gastric or small bowel surgery involving any extent of gastric or small bowel resection
• Lactating subjects are not eligible unless they have agreed to not breastfeed their infants. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing subject with silmitasertib. (NOTE: breast milk cannot be stored for future use while the nursing subject is being treated on study.)
• Subjects with a history of any other malignancy.
DRUG: Silmitasertib, DRUG: Irinotecan, DRUG: Temozolomide, DRUG: Vincristine
Neuroblastoma, Ewing Sarcoma, Osteosarcoma, Rhabdomyosarcoma, Liposarcoma
Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT) (KESETT)
Megan Wardius - mew5j@virginia.edu
NCT06907173
Inclusion Criteria:
* The patient was witnessed to have a convulsive seizure for greater than 5-minute duration
* The patient received an adequate dose of benzodiazepines. The doses may be divided.
* The last dose of a benzodiazepine was administered 5-30 minutes before study drug administration.
* Continued or recurring seizures in the Emergency Department.
* Age 1 years or older
* Known or estimated weight ≥10 Kg
Exclusion Criteria:
* Known pregnancy
* Prisoner
* Opt-out identification or otherwise known to be previously enrolled in KESETT
* Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital, or other agents defined in the MoP) for this episode of SE
* Treatment with sedatives with anticonvulsant properties other than benzodiazepines for this episode of SE(propofol, etomidate, ketamine or other agents defined in the MoP)
* Endotracheal intubation prior to enrollment
* Acute traumatic brain injury clearly precedes seizures
* Scalp injury or burn preventing EEG placement
* Known allergy or other known contraindication to KET or LEV
* Hypoglycemia \< 50 mg/dL
* Hyperglycemia \> 400 mg/dL
* Cardiac arrest / post-anoxic seizures DRUG: Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET), DRUG: Levetiracetam (LEV) (60 mg/Kg) + 3 mg/kg Ketamine (KET), DRUG: Levetiracetam (LEV) (60 mg/Kg)
Status Epilepticus
A Study to Evaluate the Efficacy and Safety of Intravenous (IV) Prasinezumab in Participants With Early-Stage Parkinson's Disease (PARAISO)
Reference Study ID Number: BN44715 https://forpatients.roche.com/ No attachments to email below. - global-roche-genentech-trials@gene.com
NCT07174310
Inclusion Criteria:
* Body weight within 40-110 kilograms (kg) (88-242 pounds \[lbs\]) and a body mass index within the range 18-34 kg/m2
* Diagnosis of idiopathic PD based on Movement Disorder Society (MDS) criteria
* Has received monotherapy treatment
* An MDS-UPDRS Part IV score of 0 at screening and prior to randomization
* Hoehn and Yahr (H\&Y) Stage 1 or 2 off medication at screening and prior to randomization
* Agreement to adhere to the contraception requirements
Exclusion Criteria:
* Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
* Medical history indicating a parkinsonian syndrome other than idiopathic PD
* Diagnosis of a significant neurologic disease other than PD
* Chronic uncontrolled hypertension DRUG: Prasinezumab, DRUG: Placebo
Parkinson's Disease