StudyFinder
Search Results Within Category "Brain & Neurology"
30 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
Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Massey, Gita, V.
NCT00904241
HM1538
Inclusion Criteria:
* All newly diagnosed patients with suspected neuroblastoma, suspected ganglioneuroblastoma, or suspected ganglioneuroma/maturing subtype seen at Children's Oncology Group (COG) institutions are eligible for this study
* There will be no penalty under any circumstances for enrollment of a patient whose definitive institutional diagnosis, or central review diagnosis, is found to be a tumor other than neuroblastoma, ganglioneuroblastoma, or ganglioneuroma/ maturing subtype
* Patients may not have received chemotherapy prior to enrollment on ANBL00B1 and procurement of study-related tissues with the following exception:
* Patients that in the opinion of the treating physician are too ill to undergo pre-treatment tissue biopsy and require EMERGENT chemotherapy may be enrolled on ANBL00B1; documentation of the emergent nature of therapy initiation is required
* It is required that a good faith effort (documented by specimen tracking) be made to submit a neuroblastoma sample (tumor, metastasis, and/or tumor-involved bone marrow) of sufficient quality for MYCN analysis in the Neuroblastoma Reference Laboratory in order for any newly diagnosed patient to be enrolled on ANBL00B1; this should be obtained prior to initiation of therapy
* Exceptions
* In rare cases, patients may be deemed too ill to undergo pre-treatment tissue biopsy and require EMERGENT therapy; the following eligibility guidelines apply to these cases:
* For presumed INSS stage 4S patients: Efforts to submit tumor tissue (e.g., primary tumor, skin nodule, or metastatic site) within 96 hours of EMERGENT therapy initiation should be made; however, if the child is deemed too unstable for such a procedure they may still be enrolled as long as pre-treatment peripheral blood and serum have been submitted
* For all other INSS stages: tumor tissue should be obtained as soon as possible within 96 hours of EMERGENT therapy initiation; patients without tumor tissues submitted within this time-frame are not eligible for enrollment
* Note: it may not be possible to obtain all necessary tumor biomarkers for therapy stratification in such cases; if a patient enrolled on ANBL00B1 undergoes an additional diagnostic procedure within 96 hours of initiating therapy, additional tumor specimens may be submitted to obtain biomarkers used for risk classification; the decision to perform such procedures, and/or submit these specimens, is to be made by the managing clinicians and should reflect the clinical need to know the status of such biomarkers
* Patients enrolled on ANBL1232 in Group A (either A1 or A2) will not have a tumor biopsy or resection upfront; tumor tissue submission is therefore not required for these patients to enroll on ANBL00B1; a peripheral blood and serum sample is the only specimen required to be submitted for this group of patients; should they undergo a biopsy or resection at a later date tumor can be submitted for biomarker testing at this time
* 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
Exclusion Criteria:
* Patients with relapsed neuroblastoma who were not enrolled on ANBL00B1 at original diagnosis are NOT eligible; samples should be submitted as part of the ABTR04B1 protocol OTHER: Cytology Specimen Collection Procedure, OTHER: Laboratory Biomarker Analysis
Ganglioneuroblastoma, Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Regional Neuroblastoma, Stage 4 Neuroblastoma, Stage 4S Neuroblastoma
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
Neuroblastoma Maintenance Therapy Trial (NMTT)
BCC Enroll - BCCEnroll@pennstatehealth.psu.edu
Gowda, Madhu, S
NCT02679144
HM20015342
Inclusion Criteria:
* All patients must have a pathologically confirmed diagnosis of neuroblastoma, \< 30.99 years of age and classified as high risk at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
* All patients must be in complete remission (CR):
• No evidence of residual disease on scan
• No evidence of disease metastatic to bone marrow. * Specific Criteria by Stratum: Stratum 1/1B: All patients must have completed standard upfront therapy that replicates treatment which patients who were enrolled on ANBL0032 received, including: intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by: consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy, followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;. All subjects on Stratum 1/B must have also met the following criteria: • A pre-transplant disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR (partial response) for primary site, soft tissue metastases and bone metastases. Patients who meet those criteria must also meet the protocol-specified criteria for bone marrow response prior to transplant as outlined below: No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy. Stratum 2: Neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1. Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy. Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s). * Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed: * Tumor imaging studies including * Bilateral bone marrow aspirates and biopsy * This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks before enrollment. * Timing from prior therapy: Stratum 1/1B: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy. Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy. * Patients must have a Lansky or Karnofsky Performance Scale score of \> 50% and patients must have a life expectancy of ≥ 2 months. * All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below. * Patients must have adequate organ functions at the time of registration: * Hematological: Total absolute phagocyte count ≥1000/μL * Liver: Subjects must have adequate liver function * Renal: Adequate renal function * Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding. * Written informed consent in accordance with institutional and FDA (food and drug administration) guidelines must be obtained from all subjects (or patients' legal representative).
Exclusion Criteria:
* BSA (Body Surface Area) of \<0.25 m2.
* 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 hematological and bone marrow suppression effects of prior chemotherapy.
* 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. DRUG: Difluoromethylornithine (DFMO)
Neuroblastoma
Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors (A5481092)
Pfizer CT.gov Call Center - ClinicalTrials.gov_Inquiries@pfizer.com
Austin, Frances
NCT03709680
HM20017464
Inclusion:
• Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
• Age ≥2 and <21 years at the time of study entry.
• Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
• Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
• Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
• Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.
• Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
• Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
• Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit. Exclusion:
• Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
• Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
• Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
• Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
• Prior irradiation to >50% of the bone marrow (see Appendix 9).
• Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
• Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
• For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
• Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
• Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
• Hereditary bone marrow failure disorder.
• QTc >470 msec.
• History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
• Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
• Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
• Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
• Age ≥2 and <21 years at the time of study entry.
• Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
• Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
• Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
• Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.
• Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
• Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
• Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit. Exclusion:
• Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
• Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
• Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
• Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
• Prior irradiation to >50% of the bone marrow (see Appendix 9).
• Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
• Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
• For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
• Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
• Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
• Hereditary bone marrow failure disorder.
• QTc >470 msec.
• History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
• Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
• Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
Drug: Palbociclib, Drug: Temozolomide, Drug: Irinotecan, Drug: Topotecan, Drug: Cyclophosphamide
Ewing Sarcoma, Solid Tumors, Rhabdoid Tumor, Rhabdomyosarcoma, Neuroblastoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma
Ewing Sarcoma, EWS, Solid Tumor, Recurrent Solid Tumors, Refractory Solid Tumors, Bone Cancer, Bone Tumor, Bone Sarcoma, Soft Tissue Cancer, Soft Tissue Sarcoma, Recurrent Ewing Sarcoma, Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma, Pediatric Cancer, Childhood Cancer, Ewing Sarcoma Treatment, Palbociclib, CDK4/6 Inhibitor, Irinotecan, Temozolomide, Topotecan, Cyclophosphamide
Distress in the Pediatric Oncology Setting: Intervention versus Natural Adaptation
Jewell, Andrea - Andrea.Jewell@vcuhealth.org
Rohan, Jennifer
NCT04409301
HM20019000
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, Breast, Brain and Nervous System, Bones and Joints, Anus, Any Site, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Female Genital, Other Endocrine System, Urinary Bladder, Thyroid, Stomach, Soft Tissue, Small Intestine, Rectum, Prostate, Pancreas, Ovary, Other Urinary, Other Skin, Other Respiratory and Intrathoracic Organs, Other Male Genital, Other Hematopoietic
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
A Study of Suboptimally Controlled Participants Previously Taking Injectable DMDs for RMS (CLICK-MS) (CLICK-MS)
US Medical Information - eMediUSA@emdserono.com
NCT03933215
Inclusion Criteria:
• Male or female participants greater than or equal to (>=)18 years
• Signed informed consent
• Have diagnosis of RMS including RRMS and aSPMS and satisfy the approved indication for cladribine tablets as per United States Prescribing Information (USPI)
• Have time since diagnosis of RMS of at least 12 months
• Had received their last previous injectable disease-modifying drug (DMD) for at least 3 months
• Have decided to initiate treatment with cladribine tablets during routine clinical care
• Meet criteria as per the approved USPI
• Have access to a valid e-mail address
• In the opinion of the Investigator, experienced suboptimal response (lack of effectiveness, intolerability, poor adherence) to injectable DMD treatment
Exclusion Criteria:
• Have been previously treated with cladribine in any dosing form
• Transitioning from previous injectable DMD solely for administrative reasons such as relocation
• Have comorbid conditions that preclude participation
• Have any clinical condition or medical history noted as contraindication on USPI
• Are currently participating in an interventional clinical trial
• Pregnant or breastfeeding women, women who plan to become pregnant or men whose partner plans to become pregnant during the cladribine treatment period
Drug: Cladribine Tablets
Multiple Sclerosis
Multiple Sclerosis, Cladribine Tablets, Observational, Mavenclad
A Study of Suboptimally Controlled Participants Previously Taking Oral or Infusion DMDs for RMS (MASTER-2) (MASTER-2)
US Medical Information - eMediUSA@emdserono.com
NCT03933202
Inclusion Criteria:
• Signed informed consent
• Have diagnosis of RMS, including RRMS and aSPMS, and satisfy the approved indication for cladribine tablets as per United States Prescribing Information (USPI)
• Have time since diagnosis of RMS of at least 12 months
• In the opinion of the investigator, experienced suboptimal response (lack of effectiveness, intolerability, poor adherence) to oral or infusion DMD treatment other than cladribine tablets
• Had received their last previous oral DMD for at least 1 month or at least 1 dose of their last previous infusion DMD
• Have decided to initiate treatment with cladribine tablets during routine clinical care
• Meet criteria as per the approved USPI
• Have access to a valid e-mail address
Exclusion Criteria:
• Have been previously treated with cladribine in any dosing form (intravenous, subcutaneous, or oral)
• Transitioning from previous oral DMD solely for administrative reasons such as relocation
• Have comorbid conditions that preclude participation
• Have any clinical condition or medical history noted as contraindication on USPI
• Are currently participating in an interventional clinical trial
• Pregnant or breastfeeding women, women who plan to become pregnant or men whose partner plans to become pregnant during study the cladribine treatment period
Drug: Cladribine Tablets
Multiple Sclerosis
Multiple Sclerosis, Cladribine Tablets, Observational, Mavenclad
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
Virginia Commonwealth University Stress Reduction Study
Hadley Rahrig, M.S. - rahrighm@mymail.vcu.edu
NCT04190030
Inclusion Criteria:
• Stable medication regiment for 8 weeks prior to enrollment if taking antidepressant or anxiolytic medications. (will not be advertised but screened)
• Free of major, uncorrected sensory impairments and cognitive deficits
• Free of a certain psychiatric disorders or history thereof; specifically, a new diagnosis of a (non-acute) medical or psychiatric condition within the last 3 months, report a hospitalization over the last 3 months, report current drug abuse (e.g., recreational drug use, alcohol intake in excess of 2 drinks per day).
• Adults aged 18 - 55 years of age
• Right hand dominant (will not be advertised but screened)
• Personal SmartPhone (Android or iOS operating systems).
• Naive to meditation practice (will not be advertised but screened)
• At least a moderate level of perceived stress (scale score > 5 on the 4-item Perceived Stress Scale (PSS; reflects above-average perceived stress)
Exclusion Criteria:
• left-handed
• are unwilling or unable to complete study assessments or treatments
• report a new diagnosis of a (non-acute) medical or psychiatric condition within the last 3 months
• report a hospitalization over the last 3 months
• report current drug abuse (e.g., recreational drug use, smoke more than ? pack per day, alcohol intake in excess of 2 drinks per day)
• are prisoners
• no personal SmartPhone (Android or iOS operating systems)
Behavioral: mindfulness training, Behavioral: cognitive reappraisal training
Stress
Mindfulness
Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer (AIM-NIVO)
McFadden, Faith - mcfaddenfr@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. 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 is Food and Drug Administration (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 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) 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
* 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
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 PROCEDURE: Biospecimen Collection, BIOLOGICAL: Nivolumab
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
Virtual Walking Intervention for Neuropathic Pain in Spinal Cord Injury (VRWalk)
Hannah Palanchi - hannah.palanchi@vcuhealth.org
Trost, Zina
NCT05005026
HM20020719
Inclusion Criteria:
• The study will recruit individuals with complete injury (American Spinal Injury Association [ASIA] classification A) with lumbar, paraplegic, or low tetraplegic (C5-C7) injury. Additional criterial will include:
• persistent NP symptoms that are of daily severity of at least 4/10
• endorsement of more than 2 items on a 7-item Spinal Cord Injury Pain Instrument, SCIPI
• age of 18 - 65
• more than one-year post-injury
Exclusion Criteria:
• Not meeting injury type criteria
• Not meeting NP criteria
• Age 17 or less
• Less than a year following injury
• Inability to comprehend spoken English
• Prisoners
Other: VR Game 1, Other: VR Game 2
Spinal Cord Injuries, Neuropathic Pain
Vitamin D Supplementation on Reported Rates of Taxane-Induced Neuropathy
Autumn Lanoye, PhD - lanoyeam@vcu.edu
Hong, Susan
NCT05259527
HM20023717
Inclusion Criteria:
* Diagnosis of stage I-III cancer of any type, OR diagnosis of stage IV cancer being treated with curative intent
* Receiving or scheduled to begin taxane-based chemotherapy at Virginia Commonwealth University (VCU) Health Massey Comprehensive Cancer Center
* Vitamin D serum level \<20 ng/mL Note: study participants with Vitamin D serum level ≥20 ng/mL may be enrolled in the observational arm.
Exclusion Criteria:
* Pre-existing diagnosis of neuropathy
* Currently taking prescription Vitamin D (ergocalciferol)
* Inability to converse in English
* Pregnancy
* Chronic kidney disease (stage IV or greater)
* Known hyperparathyroidism
* Hypercalcemia: Calcium levels \>10.5 mg/dL Note: study participants with calcium levels \<10.5 mg/dL may be enrolled in the observational arm. DRUG: Ergocalciferol Capsules, DIETARY_SUPPLEMENT: Cholecalciferol Capsules
Neuropathic Pain
Neuropathic pain, Neuropathy, Vitamin-D
Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial (FASTEST)
Joseph Broderick, MD - joseph.broderick@uc.edu
Rivet, Dennis, James
NCT03496883
HM20020430
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
• Efforts to obtain informed consent per EFIC guidelines (U.S.) or adherence to country-specific emergency research informed consent regulations (Canada, Germany, Spain, U.K., Japan)
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 Activated Factor VII (rFVIIa), BIOLOGICAL: Placebo
Intracerebral Hemorrhage
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
Phase Ib/II of ARRY-614 plus either nivolumab or nivolumab+ipilimumab in advanced solid tumors
Osipova, Ekaterina - osipovak@vcu.edu
Poklepovic, Andrew, S
NCT04074967
HM20021810
drug: Nivolumab,
drug: Ipilimumab,
drug: Arry-614, Modality: Immunotherapy
Melanoma, skin, Other Urinary, Urinary Bladder, Thyroid, Stomach, Soft Tissue, Small Intestine, Rectum, Prostate, Pancreas, Ovary, Other Respiratory and Intrathoracic Organs, Other Male Genital, Other Female Genital, Other Endocrine System, Other Digestive Organ, Lung, Liver, Lip, Oral Cavity and Pharynx, Larynx, Kidney, Eye and Orbit, Ill-Defined Sites, Esophagus, Corpus Uteri, Colon, Cervix, Breast, Brain and Nervous System, Bones and Joints
DSC-MRI in Measuring Cerebral Blood Volume for Early Response to Bevacizumab in Recurrent GBM
Hess, Alison - ahess2@vcu.edu
Chen, Zhi-Jian
NCT03115333
HM20021895
Brain and Nervous System
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
Effectiveness of IVR Combined With Task-Specific Training on Hemiplegic Arm Function Following Stroke
Rahsaan Holley - holleyrj@vcu.edu
NCT05728866
Inclusion Criteria:
* Age 18 or older.
* Diagnosed as having an ischemic or hemorrhagic stroke (with documented confirmatory neuroimaging in the medical record) that occurred at least 6-months prior to study enrollment.
* Lack of full active range of motion in the involved shoulder, elbow, and wrist as the result of the injury.
* At the time of study enrollment, participant completed structured therapeutic interventions at least 2-months prior.
* Participants will not participate in Yoga, Tai-Chi, or other wellness lifestyle classes while participating in the study.
* Absence of significant cognitive impairment as determined by a Mini-Mental Status Examination score of greater than or equal to 24.
* The absence of upper extremity injury limiting functional use of the arm prior to the incident stroke.
Exclusion Criteria:
* Unable to provide informed consent.
* Sensory loss as determined by a score of 2 on the sensory item of the NIH Stroke Scale.
* Pain in the involved upper limb that could interfere with daily activities as evidenced by a pain score of 5 or greater on the Numeric Pain Rating Scale.
* History of greater than two strokes.
* Suffered a stroke less than 6-months prior to participating in the study.
* A history of, or being susceptible to, cyber-sickness (i.e., motion sickness).
* Unable to don/doff accelerometer independently, or the lack of support in the home to assist with donning/doffing device; and
* A history of seizures. PROCEDURE: VR immersive therapy
Stroke
Testing if High Dose Radiation Only to the Sites of Brain Cancer Compared to Whole Brain Radiation That Avoids the Hippocampus is Better at Preventing Loss of Memory and Thinking Ability
ctrrecruit@vcu.edu
NCT04804644
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of small cell lung cancer within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic or brain metastasis);
* Patients with de novo or recurrent small cell lung cancer are permitted.
* Brain metastases =\< 4 cm in largest diameter and outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =\< 21 days prior to study entry.
* The total tumor volume must be 30 cm\^3 or less. Lesion volume will be approximated by measuring the lesion's three perpendicular diameters on contrast enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric measurements via slice by slice contouring on a treatment planning software package can be used to calculate the total tumor volume.
* Brain metastases can be diagnosed synchronous to the initial diagnosis of small cell lung cancer or metachronous to the initial diagnosis and management of small cell lung cancer.
* Brain metastases must be diagnosed on MRI, which will include the following elements:
* REQUIRED MRI ELEMENTS
* Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D) spoiled gradient (SPGR). Acceptable 3D SPGR sequences include magnetization prepared 3D gradient recalled echo (GRE) rapid gradient echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (Brain Volume Imaging) or 3D Fast FE (field echo). The T1-weighted 3D scan should use the smallest possible axial slice thickness, not to exceed 1.5 mm.
* Pre-contrast T1 weighted imaging (3D imaging sequence strongly encouraged).
* A minimum of one axial T2 FLAIR (preferred) or T2 sequence is required. This can be acquired as a two dimensional (2D) or 3D image. If 2D, the images should be obtained in the axial plane.
* ADDITIONAL RECOMMENDATIONS
* Recommendation is that an axial T2 FLAIR (preferred) sequence be performed instead of a T2 sequence.
* Recommendation is that that pre-contrast 3D T1 be performed with the same parameters as the post-contrast 3D T1.
* Recommendation is that imaging be performed on a 3 Tesla (3T) MRI.
* Recommendation is that the study participants be scanned on the same MRI instrument at each time point.
* Recommendation is that if additional sequences are obtained, these should meet the criteria outlined in Kaufmann et al., 2020.
* If additional sequences are obtained, total imaging time should not exceed 60 minutes.
* If additional metastases not known at the time of registration/randomization or seen in the MRI used for eligibility are subsequently found on the radiation therapy (RT) planning MRI such that the total intacranial volume exceeds 30 cm\^3, the patient is still considered eligible.
* History/physical examination
* Age \>= 18
* Karnofsky performance status of \>= 70
* Creatinine clearance \>= 30 ml/min
* Following the diagnosis of brain metastases, patients can initiate and treat with systemic (chemotherapy and/or immunotherapy) before enrollment only if their brain metastases are asymptomatic and not located in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex). However, within 21 days prior to enrollment, brain MRI must be repeated to confirm eligibility.
* Patients with symptomatic brain metastases and/or brain metastases in eloquent locations (e.g., brainstem, pre-/post central gyrus, visual cortex) are eligible for enrollment on the trial; however, the specific treatment approach of starting with systemic therapy alone and delaying brain radiation is not recommended for these patients.
* Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted.
* Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to registration. Women of childbearing potential and men who are sexually active must use contraception while on study.
* Patients may have had prior intracranial surgical resection.
* Because neurocognitive testing is the primary goal of this study, patients must be proficient in English or French Canadian.
* The patient must provide study-specific informed consent prior to study entry.
* Patients with impaired decision-making capacity are not permitted on study.
* ELIGIBILITY CRITERIA PRIOR TO STEP 2 REGISTRATION
* The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive test will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2.
* NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.
* PRIOR TO STEP 2 REGISTRATION: The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive tests will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2.
NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.
Exclusion Criteria:
* Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT treatment. Patients may have had prior chemotherapy. Concurrent immunotherapy is permitted.
* For patients receiving fractionated SRS on an every-other-day basis, planned infusion of cytotoxic chemotherapy is not permitted between SRS treatments.
* Brainstem metastasis \> 10 cm\^3
* Prior allergic reaction to memantine.
* Patients with definitive leptomeningeal metastases.
* Known history of demyelinating disease such as multiple sclerosis.
* Contraindication to MR imaging such as implanted metal devices that are MRI-incompatible, allergy to MRI contrast that cannot be adequately addressed with pre-contrast medications, or foreign bodies that preclude MRI imaging. (Questions regarding MRI compatibility of implanted objects should be reviewed with the Radiology Department performing the MRI).
* Current use of (other N-methyl-D-aspartate \[NMDA\] antagonists) amantadine, ketamine, or dextromethorphan.
* Radiographic evidence of hydrocephalus or other architectural change of the ventricular system resulting in significant anatomic distortion of the hippocampus, including placement of external ventricular drain or ventriculoperitoneal shunt.
* Mild cases of hydrocephalus not resulting in significant anatomic distortion of the hippocampus are permitted.
* Prior radiotherapy to the brain, including SRS, WBRT, or prophylactic cranial irradiation (PCI). PROCEDURE: Biospecimen Collection, PROCEDURE: Magnetic Resonance Imaging, DRUG: Memantine Hydrochloride, OTHER: Neurocognitive Assessment, RADIATION: Stereotactic Radiosurgery, OTHER: Survey Administration, RADIATION: Whole-Brain Radiotherapy
Metastatic Lung Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Recurrent Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8
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)
• 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
The CONFORM Pivotal Trial
Aly Dechert, MS - adechert@conformalmedical.com
NCT05147792
Inclusion Criteria:
• Male or non-pregnant female aged ≥18 years
• Documented non-valvular AF (paroxysmal, persistent, or permanent)
• High risk of stroke or systemic embolism, defined as CHA2DS2-VASc score of ≥ 3
• Has an appropriate rationale to seek a non-pharmacologic alternative to long-term oral anticoagulation
• Deemed by the site investigator to be suitable for short term oral anticoagulation therapy but deemed less favorable for long-term oral anticoagulation therapy.
• Deemed appropriate for LAA closure by the site investigator and a clinician not a part of the procedural team using a shared decision-making process in accordance with standard of care
• Able to comply with the protocol-specified medication regimen and follow-up evaluations
• The subject (or legally authorized representative, where allowed) has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate institutional review board (IRB)/Regional Ethics Board (REB)/Ethics Committee (EC).
Exclusion Criteria:
• Pregnant or nursing patients and those who plan pregnancy in the period up to one year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7 days prior to index procedure.
• Anatomic conditions that would prevent performance of an LAA occlusion procedure (e.g., atrial septal defect (ASD) requiring closure, high-risk patent foramen ovale (PFO) requiring closure, a highly mobile inter-atrial septal aneurysm precluding a safe TSP, presence of a PFO/ASD closure device, history of surgical ASD repair or history of surgical LAAO closure)
• Atrial fibrillation that is defined by a single occurrence or that is transient or reversible (e.g., secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures)
• A medical condition (other than atrial fibrillation) that mandates long-term oral anticoagulation (e.g., history of unprovoked deep vein thrombosis or pulmonary embolism, or prosthetic mechanical heart valve)
• History of bleeding diathesis or coagulopathy, or patients in whom antiplatelet and/or anticoagulant therapy is contraindicated
• Documented active systemic infection
• Symptomatic carotid artery disease (defined as \>50% stenosis with symptoms of ipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke); if subject has a history of carotid stent or endarterectomy the subject is eligible if there is \<50% stenosis noted at the site of prior treatment
• Recent (within 30 days of index procedure) or planned (within 60 days post-procedure) cardiac or major non-cardiac interventional or surgical procedure
• Recent (within 30 days of index procedure) stroke or transient ischemic attack
• Recent (within 30 days of index procedure) myocardial infarction
• Vascular access precluding delivery of implant with catheter-based system
• Severe heart failure (New York Heart Association Class IV)
• Prior cardiac transplant, history of mitral valve replacement or transcatheter mitral valve intervention, or any prosthetic mechanical valve implant
• Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation)
• Platelet count \<75,000 cells/mm3 or \>700,000 cells/mm3, or white blood cell count \<3,000 cells/mm3
• Known allergy, hypersensitivity or contraindication to aspirin, heparin, or device materials (e.g., nickel, titanium) that would preclude any P2Y12 inhibitor therapy, or the patient has contrast sensitivity that cannot be adequately pre-medicated
• Actively enrolled or plans to enroll in a concurrent clinical study in which the active treatment arm may confound the results of this trial
• Unable to undergo general anesthesia
• Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol or protocol-specified medication regimen, confound the data interpretation, or is associated with a life expectancy of less than 5 years
• A condition which precludes adequate transesophageal echocardiographic assessment Echo exclusion criteria:
• Left atrial appendage anatomy which cannot accommodate a commercially available control device or the CLAAS Implant per manufacturer IFU (e.g., the anatomy and sizing must be appropriate for both the investigational (CLAAS) and a commercially available device in order to be enrolled in the trial)
• Intracardiac thrombus or dense spontaneous echo contrast consistent with thrombus, as visualized by TEE prior to implant
• Left ventricular ejection fraction (LVEF) \<30%
• Moderate or large pericardial effusion \>10 mm or symptomatic pericardial effusion, signs or symptoms of acute or chronic pericarditis, or evidence of tamponade physiology
• Atrial septal defect that warrants closure
• High risk patent foramen ovale (PFO), defined as an atrial septal aneurysm (excursion \>15 mm or length \> 15 mm) or large shunt (early \[within 3 beats\] and/or substantial passage of bubbles, e.g., \>20)
• Moderate or severe mitral valve stenosis (mitral valve area \<1.5 cm2)
• Complex atheroma with mobile plaque of the descending aorta and/or aortic arch
• Evidence of cardiac tumor
DEVICE: CLAAS, DEVICE: WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder
Atrial Fibrillation, Stroke
Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain
ctrrecruit@vcu.edu
NCT06500455
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of one of the following solid tumor malignancies within 5 years prior to registration:
* Non-small cell lung cancer
* Melanoma
* Breast cancer
* Renal cell carcinoma
* Gastrointestinal cancer
* If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest/abdomen/pelvis, positron emission tomography \[PET\]/CT, etc.) is required
* Patients must have at least 1 and up to 8 total intact brain metastases detected on a contrast-enhanced MRI performed ≤ 21 days prior to registration
* At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion with a maximum diameter as measured on any orthogonal plane (axial, sagittal, coronal) of ≥ 1.0 cm and ≤ 3.0 cm
* All brain metastases must be located outside of the brainstem and ≥ 5 mm from the optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension
* Note: brainstem metastases per the MRI within 21 days of registration are an exclusion criterion; however, if the MRI used for treatment planning performed within 7 days of SRS/FSRS reveals a brainstem metastasis, the patient remains eligible if the patient is considered an appropriate radiosurgery candidate per the local investigator
* Patients must have a diagnosis-specific graded prognostic assessment ≥ 1.5
* No more than 2 lesions planned for resection if clinically indicated
* No known leptomeningeal disease (LMD)
* Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion
* Age ≥ 18 years
* Karnofsky performance status (KPS) ≥ 60
* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or prophylactic cranial irradiation \[PCI\])
* New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
* No active infection currently requiring intravenous (IV) antibiotic management
* No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
* No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy PROCEDURE: Computed Tomography, RADIATION: Fractionated Stereotactic Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, RADIATION: Stereotactic Radiosurgery
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Digestive System Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm, Metastatic Melanoma, Metastatic Renal Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8
Sleep for Stroke Management and Recovery Trial (Sleep SMART)
Kayla Novitski, MPH, CCRP - kcgossel@med.umich.edu
NCT03812653
Current Inclusion Criteria, as of 6/28/2024:
• Ischemic stroke within the prior 7 days.
• NIH Stroke Scale Score ≥1 at the time of enrollment Previous Inclusion Criteria, prior to 6/28/2024: 1\. Ischemic stroke or TIA with ABCD ≥4, within prior 14 days. Exclusion Criteria (for entire time period):
• pre-event inability to perform all of own basic ADLs
• unable to obtain informed consent from subject or legally authorized representative
• incarcerated
• known pregnancy
• current mechanical ventilation (can enroll later if this resolves) or tracheostomy
• current use of positive airway pressure, or use within one month prior to stroke
• anatomical or dermatologic anomaly that makes use of CPAP interface unfeasible
• severe bullous lung disease
• history of prior spontaneous pneumothorax or current pneumothorax
• hypotension requiring current treatment with pressors (can enroll later if this resolves)
• other specific medical circumstances that conceivably, in the opinion of the site PI, could render the patient at risk of harm from use of CPAP
• massive epistaxis or previous history of massive epistaxis
• cranial surgery or head trauma within the past 6 months, with known or possible CSF leak or pneumocephalus
• recent hemicraniectomy or suboccipital craniectomy (i.e. those whose bone has not yet been replaced), or any other recent bone removal procedure for relief of intracranial pressure
• current receipt of oxygen supplementation \>4 liters per minute
• current contact, droplet, respiratory/airborne precautions
• Ischemic stroke within the prior 7 days.
• NIH Stroke Scale Score ≥1 at the time of enrollment Previous Inclusion Criteria, prior to 6/28/2024: 1\. Ischemic stroke or TIA with ABCD ≥4, within prior 14 days. Exclusion Criteria (for entire time period):
• pre-event inability to perform all of own basic ADLs
• unable to obtain informed consent from subject or legally authorized representative
• incarcerated
• known pregnancy
• current mechanical ventilation (can enroll later if this resolves) or tracheostomy
• current use of positive airway pressure, or use within one month prior to stroke
• anatomical or dermatologic anomaly that makes use of CPAP interface unfeasible
• severe bullous lung disease
• history of prior spontaneous pneumothorax or current pneumothorax
• hypotension requiring current treatment with pressors (can enroll later if this resolves)
• other specific medical circumstances that conceivably, in the opinion of the site PI, could render the patient at risk of harm from use of CPAP
• massive epistaxis or previous history of massive epistaxis
• cranial surgery or head trauma within the past 6 months, with known or possible CSF leak or pneumocephalus
• recent hemicraniectomy or suboccipital craniectomy (i.e. those whose bone has not yet been replaced), or any other recent bone removal procedure for relief of intracranial pressure
• current receipt of oxygen supplementation \>4 liters per minute
• current contact, droplet, respiratory/airborne precautions
DEVICE: CPAP
Ischemic Stroke, Sleep Apnea, Sleep Apnea, Obstructive, Stroke, CPAP, Telemedicine, Home Sleep Apnea Test, Randomized Clinical Trial, Multicenter Trial
Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis (AMS05)
ctrrecruit@vcu.edu
NCT05285891
Inclusion Criteria:
• Have at least one clinical episode that satisfies McDonald 2017 criteria for early Multiple sclerosis (MS) for up to 2 years post-event with a dissemination in time that can be met clinically, by Magnetic Resonance Imaging (MRI), or based on oligoclonal band (OCB) positivity
• Have a length of disease duration, from first symptom, of ≤ 2 years
• For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use effective methods of contraception during the treatment period and for at least 6 months after the last dose of study drug:
• A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)
• Examples of contraceptive methods include bilateral tubal ligation, male sterilization, established hormonal contraceptives that inhibit ovulation, hormone- releasing intrauterine devices, and copper intrauterine devices
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception
• Barrier methods must always be supplemented with the use of a spermicide
Exclusion Criteria:
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• History of Primary Progressive Multiple Sclerosis (PPMS), Progressive Relapsing Multiple Sclerosis (PRMS), or Secondary Progressive Multiple Sclerosis (SPMS)
• Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing Magnetic resonance imaging (MRI)
• Known presence or history of other neurological disorders, including but not limited to the following:
• Ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage
• Central Nervous System (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
• Pregnancy or lactation a. Female participants of childbearing potential must have a negative urine pregnancy test at screening
• Any concomitant disease that may require chronic systemic treatment with corticosteroids or immunosuppressants during the course of the study
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Significant, inadequately controlled (e.g. diagnostic evaluations indicated or change in medications warranted) disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine, and gastrointestinal or any other significant disease that in the opinion of the investigator may preclude participant from participating in the study
• Functional status of NY Heart Association (NYHA) Class III or higher for heart failure at the screening visit
• Known active bacterial, viral, fungal, mycobacterial infection or other infection (including tuberculosis \[TB\] or atypical mycobacterial disease but excluding limited superficial fungal or viral infections of the skin or nails) or any severe episode of infection requiring hospitalization or treatment with Intravenous (IV) antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit
• Active or chronic infection with Human Immunodeficiency Virus (HIV), syphilis or TB (see laboratory tests below)
• 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
• Known active malignancy or active monitoring for recurrence of malignancy, including solid tumors and hematological malignancies, except basal cell, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix or the uterus that have been excised with clear margins
• Substance use disorder, including the recurrent use of alcohol and/or drugs within the past year associated with clinically significant impairment associated with failure to meet major responsibilities at work, school, or home
• Receipt of live or live-attenuated vaccines within 4 weeks prior to baseline
• Contraindications to or severe intolerance of oral or IV corticosteroids, including Intravenous (IV) methylprednisolone administered according to the country label, including:
• Psychosis not controlled by a treatment
• Hypersensitivity to any of the constituents or excipients of the preceding steroids
• Current or prior treatment with the following MS DMTs: fingolimod and other S1P receptor modulators, cladribine, natalizumab, anti-CD20 molecules, alemtuzumab, and chemotherapeutic agents
• Treatment with fumarates within 30 days prior to baseline
• Current or prior treatment with any experimental therapies (e.g., bone marrow transplant), investigational agent, or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
• Systemic corticosteroid therapy within 4 weeks prior to screening
• Laboratory test results as follows: a. Positive infection screening tests for: i. Hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) ii. Hepatitis C (HCV) antibody, if positive screen for HCV RNA Polymerase Chain Reaction (PCR) iii. Rapid plasma reagin (RPR) iv. HIV v. At or within twelve months of screening: * Positive QuantiFERON(R)-TB Gold test or positive purified protein derivative tuberculin skin test (PPD) (\>5mm induration, regardless of Bacille Calmette Guerin \[BCG\] vaccine administration) unless completion of treatment has been documented for active TB * An indeterminate QuantiFERON(R)-TB Gold test unless followed by a subsequent negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation with and clearance by local infectious disease (ID) department b. Levels of serum immunoglobulin G (IgG) \< 3.3g/L c. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)\>= 2.0 x the upper limit of normal (ULN) e. Platelet count \< 100,000 plt/mcL (\< 100 x 10\^9/L) f. Hemoglobin \< 10 g/dL g. Absolute neutrophil count \< 1.5 × 10⁹/L h. Absolute lymphocyte count \< 1.2 x 10⁹/L
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
DRUG: Ocrelizumab, DRUG: Placebo for Ocrelizumab
Multiple Sclerosis
Ocrelizumab, Multiple sclerosis, Relapse
Cardiovascular Health & Early Stress
Paula Rodriguez Miguelez - prodriguezmig@vcu.edu
NCT06557707
Inclusion Criteria:
Cohort 1
* Men and pre-menopausal women
* 18-30 years old
Cohort 2
* males and females
* 9-17 years old
Exclusion Criteria:
Cohort 1
* Evidence of cardiovascular, pulmonary, renal, hepatic or cerebral diseases
* Evidence of pregnancy or currently nursing.
* Having a history of chronic pain
* Having a history of rheumatoid arthritis
Cohort 2
* Evidence of cardiovascular, pulmonary, renal, hepatic or cerebral diseases
* Evidence of pregnancy or currently nursing.
* Having a history of chronic pain
* Having a history of rheumatoid arthritis OTHER: Childhood stress
Stress
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
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