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A Study to See if Memantine Protects the Brain During Radiation Therapy Treatment for Primary Central Nervous System Tumors
This phase III trial compares memantine to usual treatment in treating patients with primary central nervous system tumors. Memantine may block receptors (parts of nerve cells) in the brain known to contribute to a decline in cognitive function. Giving memantine may make a difference in cognitive function (attention, memory, or other thought processes) in children and adolescents receiving brain radiation therapy to treat a primary central nervous system tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
10760
All
4 Years to 17 Years old
Phase 3
NCT04939597
STU-2021-1206
Inclusion Criteria:
• >= 4 and < 18 years at time of study entry
• Patients must weigh 15 kg or greater at time of study entry
• Primary central nervous system tumors that have not received prior cranial radiotherapy
• Planned focal, cranial or craniospinal radiation treatment for a primary central nervous system tumor
• The patient must have receptive and expressive language skills in English, French or Spanish since the neurocognitive function and quality of life (QOL) assessment instruments are available in these languages only
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 4 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 male; 0.8 female
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 male; 1 female
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 male; 1.2 female
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 male; 1.4 female
• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 male; 1.4 female
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
• The patient must be able to undergo magnetic resonance imaging
• 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:
• Life expectancy of less than 18 months
• Pre-existing conditions:
• Any contraindication or allergy to study drug (memantine or placebo)
• Intractable seizures while on adequate anticonvulsant therapy, defined as more than one seizure per month for the past 2 months or since initiating anticonvulsant therapy
• History of neurodevelopmental disorder such as Down syndrome, Fragile X, William's Syndrome, intellectual disability (presumed intelligence quotient [IQ] < 70), etc
• Co-morbid systemic illnesses, psychiatric conditions, social situations, or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or would limit compliance with the study requirements
• Patients with a motor, visual, or auditory condition that precludes participation in computerized neurocognitive assessments
• Patients with any medical condition or taking medications that lead to alterations of urine pH towards the alkaline condition (e.g., renal tubular acidosis, carbonic anhydrase inhibitors, sodium bicarbonate)
• Personal history of prior cranial or craniospinal radiotherapy is not allowed
• Note: Prior anti-cancer therapy including surgery, chemotherapy, targeted agents are allowed as per standard of care clinical treatment guidelines
• Female patients who are pregnant are excluded since fetal toxicities and teratogenic effects have been noted for the study drug. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who do not agree to use an effective contraceptive method for the duration of their study participation
Procedure: Biospecimen Collection, Procedure: Cognitive Assessment, Procedure: Magnetic Resonance Imaging, Drug: Memantine Hydrochloride, Drug: Placebo Administration, Other: Questionnaire Administration
Brain and Nervous System, Central Nervous System Carcinoma
Children’s Health
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
This phase I/II trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
13954
All
12 Months to 30 Years old
Phase 1/Phase 2
NCT04870944
STU-2023-0600
Inclusion Criteria:
• Parts A and B1: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• Part B2 (relapsed/refractory osteosarcoma): Patients must be >= 12 months and =< 30 years of age at the time of study enrollment
• Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
• Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
• Part B1: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27M-mutant diffuse midline gliomas previously treated with radiation therapy
• Part B2: Patients with relapsed or refractory osteosarcoma
• Part A: Patients must have either measurable or evaluable disease
• Part B1 and B2: Patients must have measurable disease
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. Patients must have a Karnofsky or Lansky score >= 50%
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
• Solid tumor patients: >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 30 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy [XRT]/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to CBL0137
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
• For patients with solid tumors without known bone marrow involvement:
• Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a creatinine based on age/gender as follows (performed within 7 days prior to enrollment unless otherwise indicated):
• Age: Maximum serum creatinine (mg/dL)
• 1 to < 2 years: 0.6 (male); 0.6 (female)
• 2 to < 6 years: 0.8 (male); 0.8 (female)
• 6 to < 10 years: 1 (male); 1 (female)
• 10 to < 13 years: 1.2 (male); 1.2 (female)
• 13 to < 16 years: 1.5 (male); 1.4 (female)
• >= 16 years: 1.7 (male); 1.4 (female)
• Patients with solid tumors:
• Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
• Patients with solid tumors:
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
• Shortening fraction of >= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated)
• Ejection fraction of >= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
• Corrected QT (QTC) < 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
• Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
• Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
• Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
• Patients with known peripheral vascular disease are excluded
• Patients with a history of pro-thrombotic disorder are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspirate, Procedure: Bone Marrow Biopsy, Procedure: Echocardiography, Drug: FACT Complex-targeting Curaxin CBL0137
Lymphoma, Recurrent Osteosarcoma, Recurrent Malignant Solid Neoplasm, Recurrent Lymphoma, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Osteosarcoma, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Primary Malignant Central Nervous System Neoplasm, Brain and Nervous System, Bones and Joints, Diffuse Midline Glioma, H3 K27M-Mutant, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma
Children’s Health
VITAS: Atezolizumab in Combination With Chemotherapy for Pediatric Relapsed/Refractory Solid Tumors
This trial is a multi-center, non-randomized, open-label Phase I/II study evaluating the feasibility and efficacy of vincristine, irinotecan, temozolomide, and atezolizumab in children with relapsed/refractory solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
108757
All
6 Months to 18 Years old
Phase 1/Phase 2
NCT04796012
STU-2021-0606
Inclusion Criteria:
• Signed informed consent
• Relapsed or refractory solid tumor after at least one prior course of therapy.
• Hodgkin lymphoma or non-Hodgkin lymphoma are not permitted.
• Patients with CNS malignancy or asymptomatic CNS metastases may be enrolled, provided all of the following criteria are met.
• No metastatic or primary disease affecting the brainstem, midbrain, pons, or cerebellum, or within 10 mm of optic nerve
• No history of leptomeningeal disease
• No history of intracranial or spinal cord hemorrhage
• No evidence of progression of neurologic deficit, in the investigator's judgment, within 7 days prior to initiation of study medications.
• Must have histologically confirmed rhabdomyosarcoma (RMS) for RMS efficacy cohort.
• Age ≥ 6 months and ≤ 18 years
• Lansky Performance Status (patients < 16 years old) or Karnofsky Performance Status (patients ≥ 16 years old) ≥ 50
• Ability to comply with the study protocol, in the investigator's judgment
• For RMS efficacy cohort, disease must be measurable as defined by RECIST v1.1.
• For the feasibility cohort, disease must be evaluable, but patients enrolled in the feasibility cohort will be prospectively assessed for measurable disease, RMS patients will also be included in the RMS efficacy cohort.
• Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
• Availability of a tumor specimen suitable for determination of PD-L1 status, either from initial diagnosis or from a recurrence.
• For PD-L1 staining to be performed at the central site, a formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report prior to study enrollment.
• Patients for whom the required number of slides are not available may still be eligible to enroll on study with PI approval
• For the RMS efficacy cohort, it will be required that at least 8 of 17 patients have PD-L1(+) tumor. PD-L1 status will be determined at time of enrollment for all patients. When the maximum allowable number of PD-L1(-) patients has been enrolled and treated on study, PD-L1 positivity will be required for all further enrolled patients.
• Staining will be performed in the central site CAP/CLIA-certified laboratory using the 22c3 antibody for immunohistochemical analysis
• PD-L1(+) status will be defined as staining on ≥1% of tumor cells or ≥1% of stroma.
• For the feasibility cohort, PD-L1 positivity is not required but will be performed centrally in all cases for exploratory biomarker studies.
• Adequate organ and marrow function as defined by the following laboratory values obtained within 21 days prior to initiation of study medication.
• For patients without known bone marrow involvement:
• Absolute neutrophil count ≥ 1.0 x 10^9 / L (1000/µL) without granulocyte colony-stimulating factor support (≥14 days after the last dose of a long-acting growth factor such as pegfilgrastim, or 7 days after short-acting growth factor)
• Absolute lymphocyte count ≥ 0.5 x 10^9 / L (500/µL)
• Platelet count ≥ 75 x 10^9 / L (75,000/µL) without transfusion in the last 7 days
• Patients with known bone marrow metastatic disease will be eligible for the study if they meet the following criteria:
• Patients with documented liver metastases: AST and ALT ≤ 5 x ULN
• Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
• Absolute neutrophil count (ANC) ≥ 750/mm^3
• Absolute lymphocyte count ≥ 0.4 x 10^9 / L (400/µL)
• Platelet count ≥ 50,000/mm^3 (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions)
• These patients will not be evaluable for hematologic toxicity. At least 4 of 6 patients in the feasibility cohort must be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.
• Total bilirubin ≤1.5 x upper limit of normal (ULN) for age (Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN)
• AST (SGOT) and ALT (SPGT) ≤ 2.5 x ULN for age
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• Creatinine ≤ 1.5 x ULN for age or creatinine clearance (or radioisotope glomerular filtration rate) ≥ 70 mL/min/1.73 m2
• Left ventricular ejection fraction ≥ 50% or shortening fraction ≥ 30%
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Patients may be transfused to meet this criterion.
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV and hepatitis B surface antigen (HBsAg) tests at screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
• Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, vincristine, and temozolomide. Women must refrain from donating eggs during this same period.
• A woman is considered to be of childbearing potential if she is postmenarchal, 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), regardless of sexual orientation or marital status.
• Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, 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 patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
• With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of less 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, irinotecan, and temozolomide. Men must refrain from donating sperm during this same period.
• 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 patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
Exclusion Criteria:
• Pregnancy or breast-feeding:
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study treatment.
• Medical conditions that are excluded:
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Guillain-Barré syndrome, multiple sclerosis, or Kawasaki syndrome with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met at study initiation: (1) Rash must cover less 10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled tumor-related pain
• Patients requiring pain medication must be on a stable regimen at study entry for at least 2 weeks. Intermittent use of as-needed medication is allowed during this period.
• Clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (at the discretion of the treating physician)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of severe asthma or uncontrolled asthma
• Dyspnea at rest or requirement for supplemental oxygen
• Uncontrolled seizures. Patients taking a stable dose of anticonvulsants (for 2 weeks) are permitted, as long as they are not strong inducers or inhibitors of CYP3A4.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications in the opinion of the treating investigator
• Washout periods from prior therapies:
• Myelosuppressive chemotherapy or radiotherapy within 21 days prior to starting study treatment.
• Subjects must have recovered from all acute prior treatment-related toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism).
• Non-myelosuppressive cancer therapy, such as kinase inhibitors, within 7 days prior to study treatment.
• Treatment with monoclonal antibodies with long half-lives, within 3 half-lives prior to study treatment.
• Treatment with targeted cellular therapies within 28 days prior to starting study treatment.
• Major surgical procedure, other than for diagnosis, within 30 days prior to initiation of study treatment, or anticipation of the need for a major surgical procedure during the first four cycles of the study.
• Biopsy tissue collection or placement of a vascular access device is permitted if the site has healed prior to initiation of study medications.
• For patients with CNS disease, no neurosurgical resection, brain biopsy, or stereotactic/whole-brain radiation within 30 days prior to Cycle 1, Day 1
• Treatment with a live, attenuated vaccine within 30 days prior to initiation of study treatment, or anticipation of the need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• Treatment with investigational therapy within 21 days prior to initiation of study treatment or concurrent participation with another investigational agent
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of the need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained.
• Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
• Patients with CNS disease can be receiving concurrent treatment with corticosteroids with approval from the Principal Investigator. Patients must be receiving a stable or decreasing dose for ≥ 5 days prior to the baseline MRI scan and at the time of drug initiation. The Principal Investigator should be informed when steroid doses are increased because of declining patient status.
• Use of strong CYP3A4 inhibitors or inducers or strong UGT1A1 inhibitors within 12 days of Cycle 1, Day 1.
• Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
• Treatment with herbal cancer therapy within 1 week prior to initiation of study medications.
• Treatment with a long-acting hematopoietic growth factor (such as pegfilgrastim) within 2 weeks prior to initiation of study medications, or a short-acting hematopoietic growth factor (such as G-CSF) within 1 week prior to initiation of study medications.
• Prior treatments:
• Prior allogeneic stem cell or solid organ transplantation
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies to include all anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Subjects must not have previously progressed while receiving regimens that include irinotecan or temozolomide. Patients who have received irinotecan or temozolomide and did not progress while on these medications are eligible.
• Known ongoing or untreated infection, including, but not limited to bacteremia, active tuberculosis, or severe pneumonia
• Active tuberculosis
• Current treatment with anti-viral therapy for HBV
• Active hepatitis C
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Known allergy or hypersensitivity to any component of the study medications
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
Drug: Atezolizumab, Drug: Vincristine, Drug: Irinotecan, Drug: Temozolomide
Lymphoma, Rhabdomyosarcoma, Solid Tumor, Brain and Nervous System, Colon, Soft Tissue
Relapsed solid tumor, Refractory solid tumor, Rhabdomyosarcoma
UT Southwestern; Children’s Health
A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors (FIREFLY-1)
FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known BRAF alteration.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
10760
All
6 Months to 25 Years old
Phase 2
NCT04775485
STU-2022-0878
Inclusion Criteria:
• Age 6 months to 25 years with:
• Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF alteration
• Arm 3: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion
• Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating BRAF alteration
• Must have received at least one line of systemic therapy and have evidence of radiographic progression
• Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria
Exclusion Criteria:
• Patient's tumor has additional previously-known activating molecular alterations
• Patient has symptoms of clinical progression in the absence of radiographic progression
• Known or suspected diagnosis of neurofibromatosis type 1 (NF-1)
• Other inclusion/exclusion criteria as stipulated by protocol may apply
Drug: DAY101
Advanced Solid Tumor, Brain and Nervous System, Low-grade Glioma
Children’s Health
A Study of Avapritinib in Pediatric Patients With Solid Tumors Dependent on KIT or PDGFRA Signaling
This is a Phase 1/2, multicenter, open-label trial of avapritinib in participants 2 to < 18 years of age with advanced relapsed/refractory (R/R) solid tumors, including central nervous system (CNS) tumors, that harbor a PDGFRA and/or KIT mutation (including non-synonymous point mutations, insertions, and deletions) or amplification, or DMG-H3K27a who have no available curative treatment options. This is a single-arm trial in which all participants will receive avapritinib. The study consists of 2 parts: dose confirmation, safety, and PK (Part 1) and initial efficacy, safety, and PK at the Part 2 recommended dose (Part 2).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Ashley Bui
183141
All
2 Years to 17 Years old
Phase 1/Phase 2
NCT04773782
STU-2021-0904
Inclusion Criteria
• Participant must be 2 to < 18 years of age at the time of signing the informed consent.
• Diagnosis
• Participant has confirmed diagnosis of R/R solid tumor, including CNS tumors, with a mutation (including non-synonymous point mutations, insertions, and deletions) in PDGFRA and/or KIT (confirmed by local mutational testing of tumor sample) that has progressed despite standard therapy and no alternative treatment option is available. Participant with R/R solid tumors with only PDGFRA and/or KIT amplifications may be included with approval from the Sponsor. OR
• Participant has confirmed diagnosis of DMG-H3K27a (confirmed by local testing of tumor sample) that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the investigator.
• Participants with CNS disease should be on a stable (≤ 10% change) or decreasing dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
• Disease extent: a. Part 1: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. b. Part 2: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For Participants with DMG-H3K27a or PDGFRA and/or KIT mutant/amplified solid tumors, including CNS tumors that have progressed despite prior therapy, who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. For up to 5 Participants with newly diagnosed DMG-H3K27a where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
• A Lansky (< 16 years of age) or Karnofsky (≥ 16 years of age) score of at least 50. If the Participant is unable to walk due to paralysis, but is mobile in a wheelchair, the participant is considered ambulatory for the purpose of assessing their performance status.
• Participant agrees to utilize contraception consistent with local regulations.
• Male participants: Are vasectomized, or agree to use condoms, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant, see Section 5.4.2), or have a female partner who is NOT of childbearing potential.
• Female participants: Agree to use effective contraception, as defined in Section
• 4.2, from the start of Screening until 6 weeks after the last dose of study treatment and have a male partner who uses a condom, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant), or have a male partner who is vasectomized with confirmed azoospermia.
• Participant can give written informed consent/assent before any study-specific Screening procedures (if feasible). Parental/legal guardian consent will be determined by local, regional, and/or national guidelines. Exclusion Criteria
• Participant has any of the following within 14 days before the first dose of study treatment:
• Platelet count < 75 × 10^9/L (< 100 × 10^9/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement.
• Absolute neutrophil count (ANC) < 1.0 × 10^9/L.
• Hemoglobin < 8.0 g/dL with no RBC transfusion ≤ 7 days prior to the measurement.
• AST or ALT > 3 × the ULN for age; except in Participants with tumor involvement of the liver who must not have AST and ALT > 5 × ULN for age.
• Total bilirubin > 1.5 × ULN for age; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN.
• Serum creatinine > 1.5 × ULN for age.
• International normalized ratio or prothrombin time (PT) > ULN (> 1.5 × ULN if on prophylactic reversible anticoagulants).
• Participant has a QTcF > 470 msec. Participant has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
• Participant has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (> 95th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second-degree heart block or third-degree heart block).
• Participant received the following systemic antineoplastic therapies:
• Temozolomide within 4 weeks prior to the first dose of study drug
• Nitrosurea within 6 weeks prior to the first dose of study drug
• Any other systemic antineoplastic therapy (including experimental therapy) within 5 half-lives or 28 days prior to the first dose of study drug, whichever is shorter.
• Focal external beam radiotherapy, including stereotactic radiosurgery, within 6 weeks prior to the first dose of avapritinib to either target or nontarget lesions. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery, within 2 weeks of the first dose of avapritinib (within 6 weeks for Participants with CNS tumors). Craniospinal irradiation within 6 weeks prior to the first dose of avapritinib.
• All AEs related to other antineoplastic therapies (eg, systemic antineoplastics, radiotherapy) must have resolved to Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy and/or ototoxicity) prior to the first dose of avapritinib.
• Participant has previously received treatment with avapritinib.
• Participant received autologous stem cell transplant following myeloablative therapy or chimeric antigen receptor T cell therapy within 3 months prior to the first dose of avapritinib or prior allogeneic stem cell transplant within 1 year and no evidence of Grade 1 or greater graft-versus-host disease and no immunosuppressants for graft-versus-host disease (steroids for primary malignancy being permitted). Participants who received stem cell reinfusion following nonmyeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1.
• Participant requires ongoing treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers.
• Participant has had a major surgical procedure within 14 days of the first dose of study treatment (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
• Participant has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
• Female subjects of childbearing potential who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment.
• Participant is pregnant, as documented by a serum β-hCG pregnancy test consistent with pregnancy obtained at Screening and within 72 hours before the first dose of study treatment. Participants with β-hCG values that are within the range for pregnancy but are not pregnant (false-positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (premenarchal, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) do not require a serum β-hCG test.
• Participant is breastfeeding.
• Participant has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the Participant; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
• History of thrombosis requiring treatment within the past 6 months. This exclusion does not apply to catheter-related thrombosis if the catheter has been removed and did not require any other treatment in the previous 3 months.
• Participants who require anticoagulants, with the exception of stable doses of prophylactic reversible anticoagulants.
• Participants who are unable to swallow tablets (in Part 1) or minitablets (in Part 2) within the sprinkle capsules.
• Participants with a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within the past year, or radiographic evidence of hemorrhage on Screening MRI. Exceptions are: Participants with primary CNS tumors (provided they have not had CNS bleeding within 2 weeks of the first dose of avapritinib) or Participants with punctate hemorrhages < 3 mm.
• History of a seizure disorder that is not well controlled on current antiepileptic medications.
• Participant is unwilling or unable to comply with scheduled visits, treatment administration plan, laboratory tests, or other study procedures and study restrictions.
• Participant must be 2 to < 18 years of age at the time of signing the informed consent.
• Diagnosis
• Participant has confirmed diagnosis of R/R solid tumor, including CNS tumors, with a mutation (including non-synonymous point mutations, insertions, and deletions) in PDGFRA and/or KIT (confirmed by local mutational testing of tumor sample) that has progressed despite standard therapy and no alternative treatment option is available. Participant with R/R solid tumors with only PDGFRA and/or KIT amplifications may be included with approval from the Sponsor. OR
• Participant has confirmed diagnosis of DMG-H3K27a (confirmed by local testing of tumor sample) that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the investigator.
• Participants with CNS disease should be on a stable (≤ 10% change) or decreasing dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
• Disease extent: a. Part 1: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. b. Part 2: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For Participants with DMG-H3K27a or PDGFRA and/or KIT mutant/amplified solid tumors, including CNS tumors that have progressed despite prior therapy, who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. For up to 5 Participants with newly diagnosed DMG-H3K27a where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
• A Lansky (< 16 years of age) or Karnofsky (≥ 16 years of age) score of at least 50. If the Participant is unable to walk due to paralysis, but is mobile in a wheelchair, the participant is considered ambulatory for the purpose of assessing their performance status.
• Participant agrees to utilize contraception consistent with local regulations.
• Male participants: Are vasectomized, or agree to use condoms, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant, see Section 5.4.2), or have a female partner who is NOT of childbearing potential.
• Female participants: Agree to use effective contraception, as defined in Section
• 4.2, from the start of Screening until 6 weeks after the last dose of study treatment and have a male partner who uses a condom, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant), or have a male partner who is vasectomized with confirmed azoospermia.
• Participant can give written informed consent/assent before any study-specific Screening procedures (if feasible). Parental/legal guardian consent will be determined by local, regional, and/or national guidelines. Exclusion Criteria
• Participant has any of the following within 14 days before the first dose of study treatment:
• Platelet count < 75 × 10^9/L (< 100 × 10^9/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement.
• Absolute neutrophil count (ANC) < 1.0 × 10^9/L.
• Hemoglobin < 8.0 g/dL with no RBC transfusion ≤ 7 days prior to the measurement.
• AST or ALT > 3 × the ULN for age; except in Participants with tumor involvement of the liver who must not have AST and ALT > 5 × ULN for age.
• Total bilirubin > 1.5 × ULN for age; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN.
• Serum creatinine > 1.5 × ULN for age.
• International normalized ratio or prothrombin time (PT) > ULN (> 1.5 × ULN if on prophylactic reversible anticoagulants).
• Participant has a QTcF > 470 msec. Participant has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
• Participant has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (> 95th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second-degree heart block or third-degree heart block).
• Participant received the following systemic antineoplastic therapies:
• Temozolomide within 4 weeks prior to the first dose of study drug
• Nitrosurea within 6 weeks prior to the first dose of study drug
• Any other systemic antineoplastic therapy (including experimental therapy) within 5 half-lives or 28 days prior to the first dose of study drug, whichever is shorter.
• Focal external beam radiotherapy, including stereotactic radiosurgery, within 6 weeks prior to the first dose of avapritinib to either target or nontarget lesions. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery, within 2 weeks of the first dose of avapritinib (within 6 weeks for Participants with CNS tumors). Craniospinal irradiation within 6 weeks prior to the first dose of avapritinib.
• All AEs related to other antineoplastic therapies (eg, systemic antineoplastics, radiotherapy) must have resolved to Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy and/or ototoxicity) prior to the first dose of avapritinib.
• Participant has previously received treatment with avapritinib.
• Participant received autologous stem cell transplant following myeloablative therapy or chimeric antigen receptor T cell therapy within 3 months prior to the first dose of avapritinib or prior allogeneic stem cell transplant within 1 year and no evidence of Grade 1 or greater graft-versus-host disease and no immunosuppressants for graft-versus-host disease (steroids for primary malignancy being permitted). Participants who received stem cell reinfusion following nonmyeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1.
• Participant requires ongoing treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers.
• Participant has had a major surgical procedure within 14 days of the first dose of study treatment (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
• Participant has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
• Female subjects of childbearing potential who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment.
• Participant is pregnant, as documented by a serum β-hCG pregnancy test consistent with pregnancy obtained at Screening and within 72 hours before the first dose of study treatment. Participants with β-hCG values that are within the range for pregnancy but are not pregnant (false-positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (premenarchal, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) do not require a serum β-hCG test.
• Participant is breastfeeding.
• Participant has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the Participant; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
• History of thrombosis requiring treatment within the past 6 months. This exclusion does not apply to catheter-related thrombosis if the catheter has been removed and did not require any other treatment in the previous 3 months.
• Participants who require anticoagulants, with the exception of stable doses of prophylactic reversible anticoagulants.
• Participants who are unable to swallow tablets (in Part 1) or minitablets (in Part 2) within the sprinkle capsules.
• Participants with a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within the past year, or radiographic evidence of hemorrhage on Screening MRI. Exceptions are: Participants with primary CNS tumors (provided they have not had CNS bleeding within 2 weeks of the first dose of avapritinib) or Participants with punctate hemorrhages < 3 mm.
• History of a seizure disorder that is not well controlled on current antiepileptic medications.
• Participant is unwilling or unable to comply with scheduled visits, treatment administration plan, laboratory tests, or other study procedures and study restrictions.
Drug: avapritinib
Sarcoma, Brain and Nervous System, Solid Tumor, Unspecified, Child, Relapsed Solid Neoplasm, CNS Tumor
KIT, PDGFRA, Relapsed/Refractory Solid Tumor, Glioma, H3K27M, DMG-H3K27a
Children’s Health
Study to Assess the Efficacy and Safety of MT-3921 in Subjects With Acute Traumatic Cervical Spinal Cord Injury
The purpose of this study is to compare the efficacy and safety of intravenous (IV) infusions of MT-3921 to placebo in subjects with acute traumatic cervical spinal cord injury. Subjects meeting eligibility criteria will enter the 6-month double-blind period. Subjects will be randomized in a 2:1 ratio to receive MT-3921 or placebo in a double blind manner.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kristen.Hall@UTSouthwestern.edu
Salah Aoun
141400
All
18 Years to 75 Years old
Phase 2
NCT04683848
STU-2021-0267
Inclusion Criteria:
Additional screening criteria check may apply for qualification:
• Provide written informed consent prior to beginning any study procedures
• Cervical spinal cord injury that meet all of the following criteria:
• Classified as AIS A, AIS B or AIS C
• ISNCSCI neurological level of injury between C4 and C7 (for C4, the subject must have at least 1 point of motor activity between C5 to C7)
• UEMS ≤28 at Screening
• Body mass index (BMI) <40
Exclusion Criteria:
Additional screening criteria check may apply for qualification:
• Any concomitant injury that interferes with the procedures and examinations required by study protocol, including performance, interpretation or validity of neurological examinations
• Poly-traumatic Injury as defined by Injury Severity Score (ISS) values > 25
• Penetrating spinal cord injuries
• Complete transection of the spinal cord
• Any other significant pre-existing medical conditions prior to spinal cord injury or current conditions that, in the judgement of the iInvestigator, may increase the risks associated with study participation
• History of anaphylaxis or clinically significant allergic reactions to any medication
• History or presence of malignancy within the last 3 years prior to screening
• Subjects with current SARS-CoV-2 infection (COVID-19)
• Subjects with hereditary fructose intolerance
• Psychoactive substance use disorder
• Participation in any clinical trial of a new chemical entity within 12 weeks prior to Screening
• Female subjects who are pregnant or lactating
Biological: MT-3921, Biological: Placebo
Spinal Cord Injury
Parkland Health & Hospital System
A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
10760
All
3 Years to 29 Years old
Phase 2
NCT04684368
STU-2021-0638
Inclusion Criteria:
• Patients must be >= 3 years and < 30 years at the time of study enrollment
• Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG) beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 31 days prior to enrollment and start of protocol therapy [repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy [repeat if necessary]). Basal ganglia or other primary sites are excluded
• Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols)
• Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 31 days prior to study enrollment and start of protocol therapy )
• Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior to study enrollment and start of protocol therapy)
• Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery
• Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to enrollment)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 3 to < 6 years: 0.8 (male), 0.8 (female)
• 6 to < 10 years: 1 (male), 1 (female)
• 10 to < 13 years: 1.2 (male), 1.2 (female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: male (1.7), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
• Central nervous system function defined as:
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
• Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.
• 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
• NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
• English-, Spanish-, or French- speaking
• Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive and quality of life assessments
• No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with NF1 will be allowed to participate
• Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery
• Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires
Exclusion Criteria:
• Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
• Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis
• Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids
• Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination)
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs
• Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Procedure: Biospecimen Collection, Drug: Carboplatin, Drug: Etoposide, Biological: Filgrastim, Drug: Ifosfamide, Procedure: Magnetic Resonance Imaging, Drug: Mesna, Biological: Pegfilgrastim, Procedure: Peripheral Blood Stem Cell Transplantation, Other: Questionnaire Administration, Radiation: Radiation Therapy, Radiation: Radiation Therapy, Procedure: Second-Look Surgery, Drug: Thiotepa
Choriocarcinoma, Central Nervous System Nongerminomatous Germ Cell Tumor, Brain and Nervous System, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor, Pineal Region Germ Cell Tumor, Pineal Region Immature Teratoma, Pineal Region Yolk Sac Tumor, Suprasellar Germ Cell Tumor
UT Southwestern; Children’s Health
Cool Prime Comparative Effectiveness Study for Mild HIE (COOLPRIME)
To determine effectiveness of therapy to improve neurodevelopmental outcomes in infants with mild HIE. To determine the adverse effects of Therapeutic Hypothermia (TH) in mild HIE on the neonate and his/her family. Determine heterogeneity of the treatment effect across key subgroups obtained in the first 6 hours after birth prior to the decision to initiate therapy.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Pollieanna.Sepulveda@UTSouthwestern.edu
Lina Chalak
35027
All
35 Weeks and over
NCT04621279
STU-2022-0714
Inclusion Criteria:
Infants must meet all 3 inclusion criteria
• Neonates born at ≥ 35 0/7 weeks
• Mild Encephalopathy on neonatal neurologic exam within 6 hours after birth: defined as presence of at least 2 signs of mild, moderate, or severe encephalopathy with no more than 2 signs in the moderate or severe category.
• Perinatal Acidosis based on at least one of the following (A or B):
• pH ≤ 7.00 in any cord or first infant gas (arterial, venous, or capillary) within ≤ 60 min OR base deficit ≥ 16 in any cord or first infant gas (arterial, venous or capillary) within ≤ 60 min
• If pH is between 7.01 and 7.15, OR base deficit is between 10 and 15.9 mmol/liter, OR blood gas is not available, an acute perinatal event is an additional criteria required (see below definition) An acute perinatal event is defined by at least one of the following:
• Apgar score at 10 min ≤ 5
• Continued need for resuscitation at 10 min (chest compressions, bag mask ventilation, or positive pressure ventilation)
• Uterine rupture, placental abruption, cord accident (prolapse, rupture, knot or tight nuchal cord)
• maternal trauma, maternal hemorrhage, or cardiorespiratory arrest
• fetal exsanguination from either vasa previa or feto-maternal hemorrhage, shoulder dystocia
• Any evidence suggestive of acute perinatal event. Infants are still eligible for enrollment in the COOLPRIME study if the cord or infant's first blood gas (arterial, venous, or capillary) is obtained >60 minutes of life.
Exclusion Criteria:
• Gestational age at birth < 35 0/7 weeks
• Birth weight < 1800gm
• Head circumference <30cm
• Congenital or chromosomal anomaly associated with abnormal neurodevelopment or death
• Moderate or Severe HIE of 3 or more moderate or severe abnormalities on COOLPRIME Sarnat exam within 6 hours of life
• Any seizures within first six hours of life
• Redirection of care is being considered
Procedure: Normothermia, Procedure: Whole body therapeutic hypothermia
Brain and Nervous System, Mild Hypoxic Ischemic Encephalopathy of Newborn
mild HIE (Hypoxic Ischemic Encephalopathy), neonatal encephalopathy, brain ischemia, brain hypoxia
UT Southwestern; Children’s Health; Parkland Health & Hospital System
CLOZAPINE Response in Biotype-1
The CLOZAPINE study is designed as a multisite study across 5 sites and is a clinical trial, involving human participants who are prospectively assigned to an intervention. The study will utilize a stringent randomized, double-blinded, parallel group clinical trial design. B2 group will serve as psychosis control with risperidone as medication control. The study is designed to evaluate effect of clozapine on the B1 participants, and the effect that will be evaluated is a biomedical outcome. The study sample will be comprised of individuals with psychosis, including 1) schizophrenia, 2) schizoaffective disorder and 3) psychotic bipolar I disorder. The investigators plan to initially screen and recruit n=524 (from both the existing B-SNIP library and newly-identified psychosis cases, ~50% each) in order to enroll n=320 (B1 and B2) into the RCT.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Asha.Philip@UTSouthwestern.edu
Carol Tamminga
58406
All
18 Years to 60 Years old
Phase 4
NCT04580134
STU-2020-0989
Inclusion Criteria:
• 18-60y/o; males and females; all races and ethnicities; able to provide written informed consent; able to read, speak, and understand English; medically stable; meeting DSM-IV (SCID-based) criteria for schizophrenia, schizoaffective disorder, or bipolar I disorder with psychotic features (we will use DSM-IV to be consistent with prior B-SNIP samples); PANSS total score of ≥70 and at least one item scored ≥5 or two items scored ≥4 on PANSS Positive Subscale; normal baseline values for absolute neutrophil count (ANC above 1500/mm3)
Exclusion Criteria:
• premorbid intellectual ability estimate below 70 (WRAT-4, Word Reading subtest, age-corrected standardized score); comorbid DSM-IV diagnosis of alcohol or substance abuse in prior 1 month or substance dependence in prior 3 months; neurological (e.g., seizure disorder, stroke, traumatic brain injury with a loss of consciousness ≥ 30min) or severe medical condition (e.g., decompensated cardiovascular disorder, AIDS) that may affect central nervous system function; concomitant medications known to affect EEG properties (i.e., lithium, anticonvulsants, benzodiazepines) or strong CYP 1A2 inhibitors (e.g., ciprofloxacin, enoxacin) or strong CYP 3A4 inducers (e.g., phenytoin, carbamazepine, phenobarbital, rifampin) which cannot be safely discontinued; vulnerable populations (e.g., pregnant, nursing, incarcerated); unwilling to use reliable means of contraception; history of neuroleptic malignant syndrome; prior treatment with clozapine, prior treatment with long-acting injectable antipsychotics that are 1-month formulations within the past 3 months and for 3-month formulations within the past 6 months; intolerable side effects to either clozapine or risperidone in lifetime, or a previously failed trial of either clozapine or risperidone at adequate doses in lifetime; history of drug reaction with eosinophilia and systemic symptoms syndrome (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS); high risk for suicide defined as more than 1 attempt in past 12 months that required medical attention, any attempt in the past 3 months or current suicidal ideation with plan and intent such that outpatient care is precluded; current homicidal ideation with plan and intent such that outpatient care is precluded.
Drug: clozapine, Drug: risperidone
Schizophrenia, Schizoaffective Disorder, Brain and Nervous System, Bipolar 1 Disorder
Schizophrenia, Bipolar, Psychosis, Biomarker, Biotype, BSNIP, B-SNIP, IEA
UT Southwestern
A Study to Evaluate Tabelecleucel in Participants With Epstein-barr Virus-associated Diseases
The purpose of this study is to assess the efficacy and safety of tabelecleucel in participants with Epstein-Barr virus (EBV) associated diseases.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Victor Aquino
10208
All
Not specified
Phase 2
NCT04554914
STU-2020-0614
Inclusion Criteria:
• Diagnosis of EBV+ disorder
• Eastern Cooperative Oncology Group performance status <= 3 for participants aged >= 16 years; Lansky score >= 20 for participants from >=1 year to < 16 years
• Adequate organ function test results, unless organ dysfunction is considered to be due to the underlying EBV-associated disease by the investigator Cohort-specific
Inclusion Criteria:
• For participants with PID LPD:
• R/R or newly diagnosed PID LPD for whom the standard first-line therapy is inappropriate, as determined by investigator. The LPD is confirmed by at least biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.
• Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification (Cheson BD, et al. J Clin Oncol. 2014;27:3059) during or after treatment or failure to achieve a CR or partial response (PR) (defined by Lugano radiographic criteria) after standard first-line therapy
• Participant may have systemic disease only, systemic and CNS disease, or CNS disease only
• For participants with AID LPD:
• R/R or newly diagnosed AID LPD for whom the standard first line therapy is inappropriate, as determined by the investigator. The LPD is confirmed by at least biopsy-proven EBV+ LPD or positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF.
• Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
• Participant may have systemic disease only, systemic and CNS disease, or CNS disease only
• For participants with AID etiology or AID attributable to immunosenescence, objective laboratory evidence of immunodeficiency
• For participants with CNS PTLD:
• R/R or newly diagnosed EBV+ CNS PTLD for whom the standard first-line therapy is inappropriate, as determined by the investigator. The CNS PTLD is histologically confirmed by at least biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.
• Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
• Participant may have systemic and CNS disease or CNS disease only
• For participants with EBV+ PTLD, including CD20-negative disease:
• Biopsy-proven EBV+ PTLD for whom standard first-line therapy (rituximab and/or chemotherapy) is inappropriate, as determined by the investigator
• Participants must have systemic disease measurable per Lugano Classification criteria, except when contraindicated or mandated by local practice, then MRI may be used
• For participants with sarcoma, including LMS, or smooth muscle tumors:
• EBV+ sarcoma or smooth muscle tumor with rapidly progressive disease defined as progressive disease per RECIST 1.1 criteria as documented radiographically within a 6-month interval prior to enrollment
• Participants with newly diagnosed EBV+ sarcoma for whom the standard first-line therapy is inappropriate, as determined by the investigator
• Biopsy-proven EBV+ sarcoma meeting one of the criteria's of pathologically confirmed EBV+ Leiomyosarcoma or EBV+ sarcoma or smooth muscle tumor
• Measurable disease using diagnostic CT and/or MRI following RECIST 1.1 criteria (Eisenhauer et al. 2009. Eur J Cancer 45[2]:228-247)
Exclusion Criteria:
• Currently active Burkitt, T-cell, natural killer/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy
• Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment, or known history of human immunodeficiency virus (HIV) infection
• Suspected or confirmed Grade >= 2 acute graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system or extensive chronic GvHD per National Institutes of Health (NIH) consensus criteria at the time of the enrollment
• Need for vasopressor or ventilatory support at the time of enrollment
• Prior therapy (in order of increasing washout period) prior to enrollment as follows:
• Within 4 weeks or 5 half-lives (whichever is shorter) for any investigational product and/ or any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression
• Within 8 weeks: prior tabelecleucel (>8 weeks prior to enrollment) is permitted if response was obtained or if usual protocol-directed therapeutic options were not exhausted, for cellular therapies (chimeric antigen receptor therapies directed at T-cells or T-cell subsets, donor lymphocyte infusion, other CTLs or virus-specific T-cells); and/or therapies which could impact tabelecleucel function (anti-thymocyte globulin, alemtuzumab)
• Any prior treatment with EBV-CTLs with the exception of tabelecleucel as above
• Women who are breastfeeding or pregnant
• Unwilling to comply with protocol specified contraceptive/reproductive restrictions from enrollment through 90 days after the last treatment
• Ongoing need for daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis (for participants with CNS disease, protocol-specified dexamethasone is permitted and concludes by the time of enrollment)
• Any conditions that may put the study outcomes at undue risk (life expectancy < 60 days or any life-threatening illness, medical condition, or organ system dysfunction)
• For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid organ transplant
• For participants with EBV+ PTLD: prior systemic therapy for PTLD
Biological: Tabelecleucel
Sarcoma, Leiomyosarcoma, Stem Cell Transplant Complications, Lymphoproliferative Disorders, Solid Organ Transplant Complications, Allogeneic Hematopoietic Cell Transplant, Brain and Nervous System, Epstein-Barr Virus (EBV)-Associated Diseases, EBV+ Post-transplant Lymphoproliferative Disease (EBV+ PTLD), EBV+ Sarcomas, EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (EBV+ PID LPD), EBV+ Lymphoproliferative Disease With Acquired (Non-congenital) Immunodeficiency (EBV+ AID LPD), EBV+ Posttransplant Lymphoproliferative Disease in Central Nervous System (EBV+ CNS PTLD)
Allogeneic, Off-The-Shelf T-cell Immunotherapy, Epstein-Barr Virus (EBV), Epstein-Barr Virus-specific Cytotoxic T lymphocyte (EBV-CTL), Solid Organ Transplant (SOT), Hematopoietic Cell Transplant (HCT), EBVision
Children’s Health
A Phase II Trial of Poly-ICLC for Low-Grade Gliomas (NF111)
This is a phase II, prospective, longitudinal, multi-center trial of poly-ICLC (Hiltonol ®) treatment for progressive low-grade gliomas in pediatric patients with NF1. The primary objective is to evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive low-grade glioma (LGG) as measured by objective tumor response rate (CR+PR) within the first 48 weeks (12 cycles) of therapy. There will also be secondary and exploratory objectives listed in the detailed description below.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
13954
All
up to 22 Years old
Phase 2
NCT04544007
STU-2021-0062
Inclusion Criteria:
• Age: Patients must be less than 22 years at the time of enrollment; there is no lower age limit.
• All participants must have an identified pathogenetic constitutional NF1 mutation OR the clinical diagnosis of NF1 using the NIH Consensus Conference criteria.
• Diagnosis: LGG (WHO Grade 1 and 2) of the brain and spinal cord are eligible. Histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings. Biopsy for histologic diagnosis is required if there is clinical suspicion for a high-grade tumor; special attention is recommended in older adolescents or young adults to the potential for malignant transformation. Patients with metastatic disease are eligible.
• Patients must meet at least one of the following criteria for progression or recurrence of a previously treated target tumor:
• Progression or recurrence on MRI.
• New or worsening neurologic symptoms attributable to the target tumor.
• For patients with OPG: visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year by examination or history, attributable to tumor.
• Measurable Disease: Patients must have two-dimensional measurable tumor >1cm2.
• Prior Therapy: Patients must have had at least one prior medical treatment for the target LGG.
• Performance Level: Patients must have a performance status of equal or > than 50 using Karnofsky for patients equal or ≥ 16 years of age and Lansky for patients < 16 years of age.
• Patients must have recovered to grade ≤1 from any acute toxicities from all prior treatments. to enroll on this study and meet time restrictions from end of prior therapy as defined below:
• Myelosuppressive chemotherapy: must have received the last dose of myelosuppressive therapy at least 4 weeks prior to study registration, or at least 6 weeks if nitrosourea.
• Investigational/biological agent: Patient must have received the last dose of other investigational, immunotherapy, or biological agent > 14 days prior to study registration or at least 5 half-lives, whichever is greater. Bevacizumab last dose > 36 days prior to enrollment.
• Radiation therapy: Patients SHOULD NOT have received prior irradiation.
• Study specific limitations on prior therapy: There is no limit on the number of prior treatment regimens.
• Growth factor(s): Must not have received any hematopoietic growth factors within 7 days of study entry or > 14 days if pegylated GCSF is used.
• Prior surgery: At the time of enrollment, must be ≥ 3 weeks from prior major surgery such as craniotomy, orthopedic surgery, abdominal surgery or ≥1 week from minor surgery and completely recovered. Port or central line placement is not considered a major surgery.
• Organ Function Requirements: All patients must have adequate organ function defined as:
• 1 Hematologic Function:
• Hemoglobin: > 8.0 gm/dl (may transfuse PRBCs)
• ANC: > 750/mm3. Must be at least 7 days after last dose of growth factor or > 14 days since last dose of pegylated GCSF
• Platelet Count: > 75,000/mm3 (transfusion independent; ≥ 7 days from last transfusion)
• 2 Renal Function: Serum creatinine which is less than 1.5 times ULN for age (as per the table below) or GFR > 70 ml/min/1.73m2 Renal Function Normal for Age Age Maximum Serum Creatinine (mg/dL) Male Female 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4 ≥ 16 years 1.7 1.4 Liver Function:
• Total bilirubin < 1.5 x ULN (Children with diagnosis of Gilbert's Syndrome will be allowed on the study regardless of their total and indirect bilirubin levels as long as the direct bilirubin is less than 3.1 mg/dL.)
• SGPT (ALT) ≤ 5 x ULN
• SGOT (AST) ≤ 5 x ULN Pulmonary Function: No evidence of dyspnea at rest, and a pulse oximetry ≥ 92%. Reproductive Function: Female patients of childbearing potential must have negative serum or urine pregnancy test within 7 days prior to the first dose of poly-ICLC. Patient must not be pregnant or breast-feeding. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, including abstinence, while being treated on this study and for 90 days following cessation of treatment.
• Patient is able to start treatment within 7 days after enrollment.
• Patients with neurological deficits must be stable for a minimum of 1 week prior to enrollment.
• Patients are only eligible if complete resection of the LGG with acceptable morbidity is not feasible, or if a patient with a surgical option refuses surgery.
• Parents/legal guardians must provide written informed consent and agree that they will comply with the study.
Exclusion Criteria:
• Prior radiation treatment for the low-grade glioma.
• Prior exposure to poly-ICLC.
• Patients currently receiving other anti-tumor therapy or experimental therapy (targeted agents, chemotherapy radiation).
• Patients with a current or prior diagnosis of malignant glioma (WHO grade III or IV).
• Patients with a prior diagnosis of malignant peripheral nerve sheath tumor or other malignancy requiring treatment in the last 48 months.
• Patients may not have fever (≥38.50 C) within 3 days of enrollment.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• Active auto-immune illness.
• Pregnant or lactating females.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 90 days after stopping study therapy are not eligible.
• Severe unresolved infection that requires systemic IV antibiotics.
• Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, impaired gastrointestinal function, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients requiring high doses of steroids. Patients may not be on immunosuppressive therapy, including corticosteroids (with the exception of physiologic replacement, defined as ≤ 0.75 mg/m2/day dexamethasone or equivalent) at time of enrollment. However, patients who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study.
Drug: Poly ICLC
NF1, Brain and Nervous System, Low-grade Glioma
Children’s Health
The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis (ExTINGUISH)
Determine the difference in the modified Rankin score at 16 weeks in participants with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis treated with "first-line" immunomodulatory therapies provided as standard-of-care, and either inebilizumab (investigational agent) or placebo.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Taylor.Hinojo@UTSouthwestern.edu
Kyle Blackburn
156805
All
18 Years and over
Phase 2
NCT04372615
STU-2021-1105
Inclusion Criteria:
• Inclusion Criteria 1. Diagnosis of NMDAR encephalitis, defined by both (a) and (b):
• A subacute onset of change in mental status consistent with autoimmune encephalitis,
• A positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories.
• Age ≥ 18 years 3. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America (USA), European Union [EU] Data Privacy Directive in the EU) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Females of childbearing potential who are sexually active with a nonsterilized male partner must agree to use a highly effective method of contraception beginning at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 6 months after the final dose of investigational product.
• Nonsterilized males who are sexually active with a female partner of childbearing potential must agree to use a highly effective method of contraception at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 3 months after the final dose of investigational product. Male patients with female partners of childbearing potential must have that female partner use at least one form of highly effective contraception, starting at least one menstrual cycle before (the male patient's) first study drug administration and continuing until at least 3 months after their male partner's last dose of the study drug.
• Willing to forego other immunomodulatory therapies (investigational or otherwise) for NMDAR encephalitis during the study.
• Patient must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent corticosteroid within 30 days prior to randomization (Day 1). In addition, patients must have received EITHER of the following treatments within 30 days before randomization.
• IVIg, at a minimum dose of 2 g/kg
• Plasma exchange or plasmapheresis, with a minimum of 5 treatments. NOTE: These treatments may be provided during the screening period, but must be completed prior to randomization.
• mRS of ≥3 at the screening visit, indicating at least moderate disability. 9. Ability and willingness to attend study visits and complete the study
Exclusion Criteria:
• Any condition that, in the opinion of the investigator, would interfere with the evaluation or administration of the investigational product, interpretation of participant safety or study results, or would make participation in the study an unacceptable risk. This specifically includes recent history (last 5 years) of herpes simplex virus encephalitis or known central nervous system demyelinating disease (e.g., multiple sclerosis).
• Presence of an active or chronic infection that is serious in the opinion of the investigator.
• Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is the longer, prior to randomization.
• Lactating or pregnant females, or females who intend to become pregnant anytime from study enrollment to 6 months following last dose of investigational agent.
• Known history of allergy or reaction to any component of the investigational agent formulation or history of anaphylaxis following any biologic therapy.
• At screening (one repeat test may be conducted to confirm results prior to randomization within the same screening period), any of the following:
• Aspartate transaminase (AST) > 2.5 × upper limit of normal (ULN)
• Alanine transaminase (ALT) > 2.5 × upper limit of normal (ULN)
• Total bilirubin > 1.5 × ULN (unless due to Gilbert's syndrome)
• Platelet count < 75,000/μL (or < 75 × 109/L)
• Hemoglobin < 8 g/dL (or < 80 g/L)
• Total white blood count <2,500 cells/mm3
• Total immunoglobulin < 600 mg/dL
• Absolute neutrophil count < 1200 cells/μL
• CD4 T lymphocyte count < 300 cells/µL
• Receipt of the following at any time prior to randomization:
• Alemtuzumab
• Total lymphoid irradiation
• Bone marrow transplant
• T-cell vaccination therapy
• Receipt of rituximab or any experimental B-cell depleting agent, unless the CD19 B-cell level has returned to above the lower limit of normal prior to randomization.
• Receipt of any of the following within 3 months prior to randomization
• Natalizumab (Tysabri®)
• Cyclosporine
• Methotrexate
• Mitoxantrone
• Cyclophosphamide
• Azathioprine
• Mycophenolate mofetil
• Severe drug allergic history or anaphylaxis to two or more food products or medicines (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid).
• Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infection.
• Confirmed positive test for hepatitis B serology (hepatitis B surface antigen and core antigen) and/or hepatitis C PCR positive at screening.
• History of cancer, apart from ovarian or extra-ovarian teratoma (also known as a dermoid cyst) or germ cell tumor, or squamous cell carcinoma of the skin or basal cell carcinoma of the skin. Squamous cell and basal cell carcinomas should be treated with documented success of curative therapy > 3 months prior to randomization.
• Any live or attenuated vaccine within 3 weeks prior to Day 1 (administration of killed vaccines is acceptable).
• Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of enrollment.
• Recurrence of previously treated NMDAR encephalitis within the last 3 or 5 years, or suspicion of symptomatic untreated NMDAR encephalitis of greater than 3 months duration at the time of screening.
Drug: Inebilizumab, Drug: Placebo
Autoimmune Encephalitis, Brain and Nervous System, Encephalitis
Inebilizumab, NMDAR encephalitis, Autoimmune Encephalitis, Rare Disease
UT Southwestern
Post-Surgical Stereotactic Radiotherapy (SRT) Versus GammaTile-ROADS (Radiation One and Done Study)
This trial will be a randomized controlled study comparing the efficacy and safety of intraoperative radiation therapy using GammaTilesTM (GT) versus SRT 3-4 weeks following metastatic tumor resection which is the current standard of care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Toral Patel
55706
All
18 Years and over
Phase 3
NCT04365374
STU-2020-1338
Inclusion Criteria:
• Patients aged 18 years old and above. Eligibility is restricted to this age group given that the battery of neurocognitive tests utilized in this protocol are not developed or validated for use in a younger population.
• One to four newly diagnosed brain metastases, identified on the screening MRI, from an extracranial primary tumor.
• One lesion, designated the index lesion, is planned for surgical resection and is to be between 2.5 cm and 5.0 cm on the screening MRI. Index lesions ≥2.0 cm but <2.5 cm are also eligible if surgery is deemed clinically necessary and appropriate for an attempted gross total resection by the neurosurgeon.
• Non-index lesions must measure < 4.0 cm in maximal extent on the screening MRI brain scan. The unresected lesions will be treated with SRT as outlined in the treatment section of the concept.
• All metastases must be located > 5 mm from the optic chiasm and outside the brainstem. Dural based metastasis are eligible.
• Previous and/or concurrent treatment with investigational or FDA approved systemic therapies (e.g., chemotherapy, targeted therapeutics, immunotherapy) is permitted and must follow protocol guidelines as follows: Systemic therapy is allowed a minimum of one week from last systemic therapy cycle to surgical resection, and one week after surgical resection to allow a minimum of one week before starting/resuming systemic therapy, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Systemic therapy is not allowed 1 day before SRT, the same day as the SRT, or 1 day after the completion of the SRT or longer, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Agents that are delivered by implant or depot injections (such as hormonal therapies) are excluded from these restrictions.
• KPS score of ≥70.
• Stable systemic disease or reasonable systemic treatment options predicting a life expectancy of ≥6 months.
• Ability to complete an MRI of the head with contrast
• Adequate renal and hepatic function to undergo surgery, in investigators opinion.
• For women of childbearing potential only, a negative urine or serum pregnancy test done <7 days prior to randomization is required. Women must be willing to notify investigator immediately if they become pregnant at any time during the trial period.
• Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment.
• Subjects must be fluent in English or Spanish language. English speaking subjects will complete Neurocognitive assessments. Non-English speaking subjects will not complete the Neurocognitive assessments as the psychometric properties for translated tests are either not known or not as robust.
• Willingness and ability to provide written informed consent and HIPAA authorization prior to performance of any study-related procedures. A legally authorized representative may provide consent if the potential subject lacks the capacity to provide consent themselves. Exclusion Criteria
• Age <18 years.
• KPS<70
• Past radiation or surgical therapy to the index lesion or the newly diagnosed non-index lesion(s) is exclusionary. However, up to a total of 2 prior courses of SRT treatment to previously diagnosed lesions are allowed as long as any treated lesions are were >15mm from the index lesion.
• Patients with >4 newly diagnosed metastases on screening MRI
• Pregnant patients.
• Primary germ cell tumor, small cell carcinoma, or lymphoma.
• Leptomeningeal metastasis (LMD). Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as radiologic or clinical evidence of leptomeningeal involvement with or without positive cerebrospinal fluid (CSF) cytology.
• Prior WBRT for brain metastases.
• Concomitant therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device.
• Comorbid psychiatric or neurologic disease or injury impacting cognition, in the opinion of the treating physician, that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
• Subjects who, in the investigator's opinion, are unable to understand the protocol or to give informed consent, have a history of poor cooperation, noncompliance with medical treatment, or difficulty in returning for follow up care.
Device: Gamma Tile-Surgically Targeted Radiation Therapy (STaRT), Radiation: Stereotactic Radiation Therapy
Brain Metastases, Brain and Nervous System
Brain, Tumor, Cancer, New Diagnosis, Metastases, GammaTile, Radiation, Cs-131
UT Southwestern
Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma
Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
up to 31 Years old
Phase 2
NCT04301843
STU-2020-1293
Inclusion Criteria:
• All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age with history of relapsed/refractory neuroblastoma.
• All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy.
• Specific Criteria by Arm: Arms 1 and 2: Subjects with no active disease: i. No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease). o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required. ii. No evidence of disease metastatic to bone marrow. Arm 3: Measurable or evaluable disease, including at least one of the following: Measurable tumor by CT or MRI; or a positive MIBG and PET; or positive bone marrow biopsy/aspirate in at least one site.
• Timing from prior therapy: Enrollment (first dose of DFMO) no later than 60 days from last dose of the most recent therapy.
• Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
• Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.
• Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells.
• Anti-GD2 Monoclonal antibodies: At least 2 weeks must have elapsed since prior treatment with a monoclonal antibody.
• XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
• Stem Cell Transplant:
• Allogeneic: No evidence of active graft vs. host disease
• Allo/Auto: ≥ 2 months must have elapsed since transplant.
• MIBG Therapy: At least 8 weeks since treatment with MIBG therapy
• Subjects must have a Lansky or Karnofsky Performance Scale score of 60% or higher.
• Life expectancy > 2 months
• All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below.
• Subjects must have adequate organ functions at the time of registration:
• Hematological: Total absolute neutrophil count ANC ≥750/μL
• Liver: Subjects must have adequate liver function as defined by AST and ALT <5x upper limit of normal (Normal=45), Bilirubin <1.5x upper limit normal (Normal=1.0). Normal PT, PTT, fibrinogen.
• Renal: Adequate renal function defined as (perform one of the following): Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or greater or a serum creatinine based on age/gender
• 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 guidelines must be obtained from all subjects (or patients' legal representative).
Exclusion Criteria:
• BSA of <0.25 m2.
• Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.
• Subjects that received a dose of DFMO in combination with etoposide are not eligible.
• 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: Eflornithine
Neuroblastoma, Brain and Nervous System
Children’s Health
Multimodal Monitoring of Cerebral Autoregulation After Pediatric Brain Injury
Various methods have been studied to evaluate autoregulation. However, there is currently no universally accepted technique to assess integrity of the cerebral autoregulation neurovascular system. In the last decade, significant progress has been achieved in developing methods to assess cerebral autoregulation by quantifying cross-correlation between spontaneous oscillations in CBF or oxygenation and similar oscillations in arterial blood pressure. In this study the investigators will analyze the relationship between spontaneous fluctuations in mean arterial blood pressure and cerebral blood flow velocity or cerebral regional oxygenation to investigate two novel methods for measuring cerebral autoregulation, Transfer Function Analysis and Wavelet Coherence after acute pediatric brain injury.
Call 214-648-5005
studyfinder@utsouthwestern.edu, DARRYL.MILES@UTSouthwestern.edu
Darryl Miles
55956
All
28 Days to 18 Years old
N/A
NCT04242602
STU 042018-056
Inclusion Criteria:
• Ages 28 days-18 years admitted to the PICU at Children's Medical Center Dallas
• Acute presentation (< 24 hour) onset of neurologic injury
• Acute neurologic injury can be due to any of the following mechanisms:
• Severe accidental or abusive traumatic brain injury
• Severe encephalopathy secondary to cardiac arrest
• Spontaneous intracranial hemorrhage
• Status epilepticus
• Stroke
• Presence of or pending placement of invasive indwelling arterial line for stand medical care
• Any patient with an ICP monitor placed as standard of care
Exclusion Criteria:
• Patients without an arterial line placed as standard of care
• Patients unable to cooperate with wearing a TCD headpiece device
• Expected death within 24-48 hours
• Inability to place NIRS probes or insonate TCD signal due to massive facial or cranial injury
• Receiving an inhalational anesthetic agent
• Hemoglobinopathy, myoglobinemia or and hyperbilirubinemia (due to inaccurate NIRS readings)
Device: Transcranial Doppler
Traumatic Brain Injury, Brain Injuries, Brain Injury, Vascular, Brain and Nervous System
Children’s Health
Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP)
A multicenter, randomized, adaptive allocation clinical trial to determine if increasing durations of induced hypothermia are associated with an increasing rate of good neurological outcomes and to identify the optimal duration of induced hypothermia for neuroprotection in comatose survivors of cardiac arrest.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Lauren.Kerich@UTSouthwestern.edu
Ava Pierce
75453
All
18 Years and over
N/A
NCT04217551
STU-2020-0185
Inclusion Criteria:
• Coma after resuscitation from out of hospital cardiac arrest
• Cooled to <34 deg C with 240 minutes of cardiac arrest
• Definitive temperature control applied
• Age ≥ 18 years
• Informed consent from legal authorized representative (LAR) including intent to maintain life support for 96 hours
• Enrollment within 6 hours of initiation of cooling
Exclusion Criteria:
• Hemodynamic instability
• Pre-existing neurological disability or condition that confounds outcome determination
• Pre-existing terminal illness, unlikely to survive to outcome determination
• Planned early withdrawal of life support
• Presumed sepsis as etiology of arrest
• Prisoner
Device: Therapeutic Hypothermia
Hypoxia-Ischemia, Brain, Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced
Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma
Parkland Health & Hospital System
Metformin in Alzheimer's Dementia Prevention (MAP)
MAP will be a multisite phase II/III 1:1 randomized controlled trial (RCT) of long acting metformin (reduced mass Glucophage XR) vs. matching placebo in 326 men and women with early and late aMCI, without diabetes, not treated with metformin, overweight or obese, aged 55 years to 90 years. The RCT will last 18 months and have 4 visits: baseline, 6-months, 12-months, and 18-months. The RCT will be preceded by a screening phase followed by randomization and a titration period in which drug/placebo will be titrated from 500 mg a day (one tablet) to 2,000 mg a day (4 tablets), in increments of 500 mg (one tablet) every 10 days. Participants will remain in the RCT on the tolerated dose, and included in analyses on an intent to treat basis. We expect the attrition rate to be 10%/year. Neuropsychological battery, clinical interviews, physical exam, and phlebotomy will be conducted at baseline and every 6 months. Brain MRI will be conducted in approximately half of the participants (186) twice, at baseline, and after the last study visit at month 18. We will also conduct brain amyloid Positron Emission Tomography (PET) using 18F-Florbetaben, and tau PET using 18F-MK6240 in half of the participants at baseline and end of the RCT. The primary clinical outcome of the study will be changes in the Free and Cued Selective Reminding Test. The secondary clinical outcome will be changes in the Alzheimer's Disease Cooperative Study Preclinical Alzheimer's Cognitive Composite. Secondary subclinical outcomes will be changes in cortical thickness AD signature areas, changes in white matter hyperintensity volume, changes in brain amyloid burden, changes in brain tau burden, and changes in plasma biomarkers of amyloid, tau, and neurodegeneration. The data coordinating center and Imaging Core is located at John Hopkins University. The PET coordinating center is located at UC-Berkeley. The Clinical Coordinating and Monitoring Center and the central laboratory will be located at Columbia. The Research pharmacy function will be shared by the University of Rochester, which will dispense randomization kits, and the University of Iowa, which will receive bulk metformin and identical matching placebo from EMD Serono.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Simosabo.Dube@UTSouthwestern.edu
Ihab Hajjar
215372
All
55 Years to 90 Years old
Phase 2/Phase 3
NCT04098666
STU-2023-0240
Inclusion Criteria:
Diagnosis of aMCI:
• Participants must have subjective memory concern reported by participant, study partner, or clinician.
• A mini-mental state exam between ≥ 22 for subjects with more than 8 years of education. For subjects with less than 8 years of education, a MMSE ≥ 20 will be allowed.
• Clinical Dementia Rating 0.5. The memory box score must be at least 0.5.
• General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit.
• Abnormal memory function documented by scoring within the education adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised.
• For early MCI:
• 9-11 for 16 or more years of education
• 5-9 for 8-15 years of education
• 3-6 for 0-7 years of education
• For late MCI
• ≤ 8 for 16 or more years of education
• ≤ 4 for 8-15 years of education
• ≤ 2 for 0-7 years of education
• Age range: 55 years to 90 years.
• Sex distribution: all eligible men and women will be included and no one will be excluded because of gender.
• Languages: fluent in English or Spanish. We have reliable, well-validated Spanish tests for all outcome measures.
• Participants without a known history of diabetes. If diabetes is diagnosed during screening (hemoglobin A1c of 6.5 % or greater) they will also be excluded. The main justification for this exclusion is the potential for these participants to be placed on other diabetes medications that may confound our study.
• General cognition and functional performance such that a diagnosis of dementia cannot be made at the time of screening based on DSM-V criteria.
• Vision and hearing must be sufficient for compliance with testing procedures.
• Must have an informant to come to all appointments or be available by telephone at follow-up visits. Study Partner Inclusion Criteria
• The study partner can provide an independent evaluation of functioning for a person enrolled in the MAP study as a participant
• The study partner agrees to attend study visits with the MAP participant or be available by telephone.
Exclusion Criteria:
• Use of metformin for any indication.
• Body mass index < 20 k/m2.
• Metformin is contraindicated in persons with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min. For persons with an eGFR of 30 to 45 mL/min, a reduction of the dose or discontinuation of the medication is recommended for those on metformin; in this range, it is also recommended that persons do not initiate metformin. Thus, participants with eGFR < 45 mL/min will not be eligible to participate.
• The risk of lactic acidosis is increased in persons with liver disease and class III or IV congestive heart failure. Thus, persons with liver disease other than non-fatty liver disease (e.g., cirrhosis) or class III or IV congestive heart failure will not be eligible to participate due to the risks of side effects.
• A history of intolerance to metformin used for indications other than diabetes.
• History of cerebrovascular accident with residual neurological deficits.
• Moderate to severe depression, indicated by a score in the Geriatric Depression Scale of 9/15 or higher.
• Dementia diagnosis
• Lack of capacity to consent
• Participants with neurologic diseases associated with neurologic deficits on clinical examination.
• Participants with other current Axis I psychiatric diagnoses such as bipolar disorder or schizophrenia.
• Alcohol or substance abuse or dependence in the past 6 months.
• Use of medications rated as being the likely cause of cognitive impairment. These include benzodiazepines in dose equivalents greater than 2 mg daily of lorazepam, and regular use of prescription narcotics.
• Normal individuals without cognitive complaints.
• Participants with uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg).
• Participants with active cancer or a history of cancer within the last two years, with the exception of squamous or basal cell carcinoma of the skin.
• Participants who for any reason may not complete the study as judged by the study physician.
• Participants planning to move to another city or state within the next 24 months.
• Participants with a known history of diabetes. The rationale for this exclusion is persons with diabetes may already be on metformin or on other medications that increase insulin levels and could confound the trial.
• Participants with diabetes discovered on screening based on American Diabetes Association criteria using HbA1c (HbA1c of 6.5% or greater). Although metformin could be a first treatment of diabetes for these participants, addition of treatments for diabetes by physicians could confound the study.
• Use of aducanumab (Aduhelm™) of any other amyloid modifying treatment for AD.
• Not able to undergo phlebotomy as reported by the participant or determined by the study coordinator or physician.
• Participants with known, suspected, or plan for becoming pregnant. Exclusion Criteria for MRI Contraindications for MRI include inability to lie flat, claustrophobia, or presence of indwelling metal objects or implants that are not MRI compatible. Exclusion Criteria for PET History of adverse reactions to radiocontrast agents.
Drug: Placebo oral tablet, Drug: extended release metformin
Mild Cognitive Impairment, Brain and Nervous System
UT Southwestern
67Cu-SARTATE™ Peptide Receptor Radionuclide Therapy Administered to Pediatric Patients With High-Risk, Relapsed, Refractory Neuroblastoma
The aim of this study is to evaluate the safety and efficacy of 67Cu-SARTATE in pediatric patients with high-risk neuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
Not specified
Phase 1/Phase 2
NCT04023331
STU-2020-1005
Inclusion Criteria:
• Participant is able and willing to provide informed consent (≥18 years), or informed consent is obtained by the parent or legal guardian for minor participants, with the minor providing age appropriate assent, according to local law and regulations;
• Life expectancy ≥ 12 weeks;
• Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has relapsed or progressed to high-risk, with failure to achieve complete response with standard therapy (defined as at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, or according to a standard high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to receive standard treatment OR who are intolerant to standard treatment;
• Adequate recovery from acute toxic effects of any prior therapy, as deemed by the Investigator or treating Sub-Investigator;
• Adequate liver function as defined by the following laboratory values obtained within 28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN);
• Adequate renal function;
• Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet count > 50 x 10 9/L; Total bilirubin <1.5 x ULN;
• Karnofsky or Lansky performance status ≥50;
• All participants must have a hematopoietic stem cell product available (minimum CD34+ cell dose is ≥2 x 10 6 cells/kg);
• Sexually active participants of reproductive potential must practice an effective method of birth control while participating on this study, to avoid possible damage to the fetus. Abstinence is considered acceptable;
• 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than that of the liver in order to move on to the therapy phase of the study.
Exclusion Criteria:
• Participants with disease of any major organ system that would compromise their ability to tolerate therapy, as deemed by the Investigator or treating Sub-Investigator;
• Any other active malignancy, or a history of prior malignancy within the past 3 years;
• History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance, oxygen requirement, clinically significant cardiac dysfunction;
• Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE;
• Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the administration of 64Cu-SARTATE;
• External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney within 12 months prior to the administration of 64Cu-SARTATE;
• Administration of any investigational agents within 21 days prior to administration of 64Cu-SARTATE;
• Treatment with long acting somatostatin analogues (administered within 28 days prior to the administration of 64Cu-SARTATE), or short acting somatostatin analogues (administered within 24 hours prior to the administration of 64Cu-SARTATE);
• Known sensitivity or allergy to somatostatin analogues;
• Previous peptide receptor radionuclide therapy (PRRT);
• Female participants who are pregnant or lactating;
• Participants who are on hemodialysis;
• QTc interval ≥ 0.45 seconds as measured by Screening ECG;
• Participants with uncontrolled infection(s);
• Any medical condition which the Investigator feels may interfere with the procedures or evaluations of the study;
• Participants 12 months and younger will be excluded from cohorts where the planned single or cumulative administered activity is modelled to deliver a radiation dose to the marrow that exceeds 2 Gy.
Drug: 67Cu-SARTATE, Drug: 64Cu-SARTATE
Neuroblastoma, Refractory Neuroblastoma, Relapsed Neuroblastoma, Brain and Nervous System
Children’s Health
Study to Compare the Efficacy and Safety of NT 201 (Botulinum Toxin) With Placebo for the Treatment of Lower Limb Spasticity Caused by Stroke or Traumatic Brain Injury (PATTERN)
The purpose of this study is to determine whether a single treatment with administration of 400 Units NT 201 (botulinum toxin) is superior to placebo (no medicine) for the treatment of lower limb spasticity caused by stroke or traumatic brain injury (Main Period). Participants will be assigned to the treatment groups by chance and neither the participants nor the research staff who interact with them will know the allocation. The following 4 to 5 treatment cycles will investigate the safety and tolerability of treatment with NT 201 (botulinum toxin) when administered in doses between 400 and 800 Units (Open Label Extension Period). All participants will receive the treatment and the dose will depend on whether only lower limb spasticity or combined upper and lower limb spasticity are treated.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Victoria.Castillo@UTSouthwestern.edu
Fatma Gul
12837
All
18 Years to 85 Years old
Phase 3
NCT03992404
STU-2019-0894
Inclusion Criteria:
• Female or male subject ≥ 18 years and ≤ 85 years at screening
• Diagnosis of lower limb spasticity with or without upper limb spasticity of the same body side caused by stroke or traumatic brain injury
• Disabling ankle flexor spasticity presenting as pes equinus or pes equinovarus
• Modified Ashworth Scale-Bohannon [MAS] score of 2 or 3 points in the ankle plantar flexor of the target lower limb (supine position, knee extended)
• Minimum passive range of motion in ankle of the target lower limb (supine position, knee extended): 10°dorsiflexion and 20°plantarflexion
• At least 4 months since last botulinum neurotoxin [BoNT] injection for treatment of spasticity or any other condition
• For subjects receiving anticoagulation therapy, the investigator confirms and documents that the subject has an:
• Activated partial thromboplastin time [aPTT] ≤ 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or
• International normalized ratio [INR] value of ≤ 2.5 (subjects on coumarins or other anticoagulants monitored by INR)
Exclusion Criteria:
• Generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert Eaton syndrome, amyotrophic lateral sclerosis) or any other significant peripheral neuromuscular dysfunction which might interfere with the study
• Bilateral lower limb paresis/paralysis/spasticity or tetraparesis/paralysis/spasticity
• Body weight < 50 kg
• Severe atrophy of the target limb muscles
• Previous, ongoing or planned treatments of spasticity with intrathecal baclofen
• Previous, ongoing, or planned treatments of spasticity in the target lower limb with any of the following procedures: Surgical Intervention; Alcohol or phenol block; Muscle afferent block
• Physiotherapy or use of orthoses or splints at the target limb initiated less than 4 weeks before screening or expected to change during the double blind phase of the study
• Current or planned treatment with parenterally administered drugs that interfere with neuromuscular transmission (e.g. intrathecal baclofen, tubocurarine type muscle relaxants used in anesthesia), or local anesthetics in the treated region within 2 weeks prior to screening
• Infection or inflammation at the injection sites
• Subjects with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, or compromised respiratory function as per investigator's clinical judgment
• Pregnancy (as verified by a positive pregnancy test) or breast feeding
Drug: NT 201, Drug: Placebo
Brain and Nervous System, Other, Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury
UT Southwestern; Parkland Health & Hospital System
Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression
Treatment resistant depression remains a major problem for individuals and society. Surgical procedures may provide relief for some of these patients. The most frequently considered surgical approach is deep brain stimulation (DBS) of a part of the brain called the subcallosal cingulate region. However, the effectiveness and safety is not well established. The investigators will use a novel approach using advanced imaging technique (magnetic resonance tractography) to evaluate the feasibility and safety of this surgical approach. An innovative method for the definition of DBS target will be applied that redefines the concept of targeting as one of targeting a symptomatic network rather than a structural brain region using subject-based brain anatomy to define the target location. The correlation between imaging findings at baseline with the mood score changes at different time points of the study will be investigated.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hamasa.Ebadi@UTSouthwestern.edu
Nader Pouratian
205161
All
21 Years to 70 Years old
N/A
NCT03952962
STU-2021-0635
Inclusion Criteria:
• Men and women (non-pregnant) between ages 21 and 70;
• DSM-5 diagnosis a current major depressive episode (MDE) for 10 years of less, recurrent or single episode with first episode after adulthood and did not start during childhood or adolescence, secondary to nonpsychotic unipolar major depressive disorder;
• Current index MDE ≥24 months duration and/or recurrent illness with at least a total of 2 lifetime episodes (including current episode >12 months);
• Treatment resistance (defined by criteria on the Antidepressant Treatment History Form (ATHF)28): Failure to respond to a minimum of four adequate depression treatments from different categories;
• Symptom severity for Screening: Hamilton Depression Rating Scale-17 item (HDRS17) ≥20;
• Symptom severity for Outcome: Montgomery Asberg Rating Scale (MADRS) ≥27 to be met at assessment one week pre-op;
• Normal brain MRI within 3 months of surgery;
• Antidepressant medication regimen has been held stable for ≥ 30 days prior to the study screening MADRS;
• Remain on stable antidepressant medication throughout the study, unless there are safety concerns;
• Montreal Cognitive Assessment (MoCA) >25;
• Able and willing to give informed consent and agree to attend regular clinic visits for at least 12 months.
Exclusion Criteria:
• DSM-5 Axis I Disorders: any lifetime history of psychotic disorder or bipolar disorder;
• Alcohol or substance use disorder within 6 months, excluding nicotine;
• History of childhood abuse (physical or sexual) 18
• Personality disorders;
• Seeking disability during the trial;
• Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or made any suicide attempt within the last year; (MADRS ≥ 5 including the day of surgery);
• No stable work history;
• Neurological/Medical condition that makes the patient, in the opinion of the surgeon, a poor candidate;
• Pregnant or has plans to become pregnant in the next 36 months;
• Unable/unable to practice birth control through the period of randomization and withdrawal of therapy;
• Subjects who have a history of a seizure disorder;
• Subjects who will be exposed to diathermy;
• Subjects who have any medical contraindications to undergoing DBS surgery (e.g. infection, coagulopathy, or significant cardiac or other medical risk factors for surgery);
• Subjects with another implanted device such as a cardiac pacemaker, defibrillator or neurostimulator;
• Subjects who have a history of hemorrhagic stroke;
• Subjects who are unable to undergo MRI;
• Subjects who are at increased risk of hemorrhage due to underlying medical conditions or medication.
Device: Abbott Laboratories Infinity™ implantable deep brain stimulation system
Treatment Resistant Depression, Undergoing Deep Brain Stimulation (DBS) Surgery
UT Southwestern
Non-Contrast Perfusion Using Arterial Spin Labeled MR Imaging for Assessment of Therapy Response in Glioblastoma
MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first. Clinically, GBM patients are imaged every 8-weeks, beginning at 10 weeks after the completion of chemoradiation, since morphological (i.e. size) changes are not anticipated earlier. However, our preliminary experience and others have shown functional changes including perfusion and diffusion as early as 3-weeks after the initiation of the treatment . Thus, our T10, T18, T26 and T34 MRI sessions will be performed along with the clinical imaging sessions, while the T3 and T6 MRI sessions will be performed additionally for this proposal. All MR imaging sessions will be scheduled within ±1 or ±2 weeks of the target time period, as indicated in the table. MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. The research MR imaging may take approximately an additional 15 minutes per each imaging session. However, the T3, and T6 MR imaging sessions will be performed additionally for the purpose of this study, with each taking approximately one hour. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Marco Da Cunha Pinho
134506
All
18 Years and over
N/A
NCT03922984
STU 032018-079
Inclusion Criteria:
• Patients with histologically proven GBM
• Newly diagnosed GBM. Prior surgery is allowed, but should not have started any other treatment such as chemotherapy, radiation treatment, and anti-angiogenic therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Women of child-bearing potential must agree to undergo a urine pregnancy screening per standard Radiology departmental protocol, in place to prevent imaging of pregnant patients. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: 1) Has not undergone a hysterectomy or bilateral oophorectomy; or 2) Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Scheduled to undergo chemoradiation.
Exclusion Criteria:
• Subjects who have had prior chemotherapy or radiotherapy.
• Subjects may not be receiving any other investigational agents at the time of enrollment.
• Subjects must not be pregnant since pregnancy is a contraindication to administration of gadolinium-based contrast agents.
• Any contraindication to MRI per Radiology Department's routine protocol, e.g. MRI-incompatible objects, including but not limited to medical devices (e.g. pacemakers, automated implantable cardioverter defibrillators, etc.) and other foreign bodies.
• Known severe allergic reaction to Gadolinium-based contrast agents.
• Patients with sickle cell disease and patients with other hemolytic anemias (low red blood count in body).
• Patients with uncontrollable claustrophobia, severe lower back pain, and uncontrollable tremors, to the point that it would render them unable to tolerate an MRI study.
Procedure: MRI with Arterial Spin Labeling (ASL)
Glioblastoma, Brain and Nervous System
magnetic resonance imaging, arterial spin labeling
UT Southwestern
A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors (LIBRETTO-121)
This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric participants with an activating rearranged during transfection (RET) alteration and an advanced solid or primary CNS tumor.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
6 Months to 21 Years old
Phase 1/Phase 2
NCT03899792
STU-2018-0444
Inclusion Criteria:
• Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies
• Evidence of an activating RET gene alteration in the tumor and/or blood
• Measurable or non-measurable disease
• Karnofsky (participants 16 years and older) or Lansky (participants younger than 16) performance score of at least 50
• Participant with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days
• Adequate hematologic, hepatic and renal function.
• Ability to receive study drug therapy orally or via gastric access
• Willingness of men and women of reproductive potential to observe conventional and effective birth control
Exclusion Criteria:
• Major surgery within two weeks prior to planned start of LOXO-292
• Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
• Clinically significant active malabsorption syndrome
• Pregnancy or lactation
• Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of LOXO-292)
• Uncontrolled symptomatic hypercalcemia or hypocalcemia
• Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension
• Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s])
Drug: LOXO-292
Papillary Thyroid Cancer, Soft Tissue Sarcoma, Infantile Fibrosarcoma, Medullary Thyroid Cancer, Infantile Myofibromatosis, Brain and Nervous System, Anklylosing Spondylitis, Bones and Joints, Ovary, Prostate, Soft Tissue
Loxo, LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Adenoma, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Colonic Neoplasms, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, Soft tissue sarcoma, Infantile Myofibromatosis, Infantile Fibrosarcoma
Children’s Health
Exploring the Effects of Corticosteroids on the Human Hippocampus
Chronic corticosteroid (CS) exposure is associated with changes in memory and the hippocampus in both humans and in animal models. The hippocampus has a high concentration of glucocorticoid receptors (GCRs), and the pre-clinical literature demonstrates shortening of apical dendrites in the CA3 region of the hippocampus and decreased neurogenesis in the dentate gyrus (DG) following CS administration. In humans, both stress and CS exposure are associated with a decline in declarative memory performance (a process mediated by the hippocampus). Impairment in declarative memory and hippocampal atrophy are reported in patients with excessive CS release due to Cushing's disease, and, by our group, in patients receiving prescription CS therapy. These findings have important implications for patients with mood disorders, as a large subset of people with major depressive disorder (MDD) show evidence of HPA axis activation, elevated cortisol and, importantly, resistance to the effects of CSs on both the HPA axis and on declarative memory. Thus, resistance to corticosteroids appears to be a consequence of MDD. this study will examine changes in declarative memory, as well as use state-of-the-art high-resolution multimodal neuroimaging, including structural and functional (i.e., task-based and resting state) MRI, in both men and women healthy controls, and, as an exploratory aim, a depressed group, given 3-day exposures to hydrocortisone (160 mg/day) or placebo. The study will translate preclinical findings to humans, provide valuable data on possible sex differences in the response to cortisol and, for the first time, identify specific hippocampal subfields (e.g., CA3/DG) in humans that are most sensitive to acute CS effects. Using resting state fMRI data and whole brain connectomics using graph theoretical approaches, we will determine the effects of cortisol exposure on functional brain networks. Furthermore, this will be the first study to use neuroimaging to compare the brain's response to CSs in people with depression vs. controls, and determine whether depressed people demonstrate glucocorticoid resistance within the hippocampus. We hypothesize that hippocampal response to acute CSs will be greatest in the CA3/DG subfield, greater in women than in men, and that depressed people will show a blunted hippocampal response to CSs compared to controls. A multidisciplinary research team with extensive experience in CS effects on the brain and hippocampal subfield neuroimaging, and a prior history of research collaboration, will conduct the project.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Shuchi.Lakhanpal@UTSouthwestern.edu
Edson Brown
10878
All
18 Years to 50 Years old
Phase 4
NCT03896659
STU-2018-0360
Inclusion Criteria:
• Men and women age 18-50 years with vision corrected to at least 20-40 (needed for fMRI tasks)
• Education of ≥ 12 years
• Baseline RAVLT total words recalled T-score ≥ 40 (normal range)
• BMI between 18.5-35.0 (neither underweight nor severely obese)
• Baseline QIDS-C ≤ 5 (virtual absence of depressive symptoms) for "healthy controls" and for the "depressed" group a QIDS-C between 11-20 (≥ moderate depressive symptoms but < very severe depressive symptoms)
Exclusion Criteria:
• History of major psychiatric illness other than MDD for the depressed group, defined as bipolar disorder, posttraumatic stress disorder, schizoaffective disorder, schizophrenia, eating disorders, or MDD with psychotic features. For the control group, a past episode of MDD (per SCID) is also exclusionary
• History of drug or alcohol use disorder
• History of neurological disorders including seizures, brain surgery, multiple sclerosis, Parkinson's disease
• Taking CNS-acting medications (e.g., antidepressants, antipsychotics, lithium, anticonvulsants, sedative/hypnotic/anxiolytics). Thus, the depressed group will be medication free.
• History of allergic reaction or medical contraindication to hydrocortisone
• Metal implants, claustrophobia, or other contraindications to MRI
• Significant medical conditions (e.g., cancer, heart disease, diabetes)
• Vulnerable population including pregnant or nursing women, prisoners, and people with intellectual disability, history of special education classes, dementia, or other severe cognitive disorders
• Current suicidal ideation, a suicide attempt in the past 12 months or more than one lifetime attempt
• History of systemic CS use in the past 12 months, lifetime cumulative use of more than 12 weeks, or recent (defined as past 28 days) inhaled CS use
• Women who are using estrogen containing oral contraceptive agents (other contraceptives are acceptable, see Protection of Human Subjects section for a list of acceptable birth control methods) or who are post- or peri-menopausal or with irregular menstrual cycles (i.e., inconsistent menstruation patterns)
Drug: Hydrocortisone Oral, Drug: Placebo Oral Tablet
Depression, Healthy Volunteers, Hydrocortisone, Psychiatric Disorders
Study to Investigate the Safety of the Transplantation of Human Glial Restricted Progenitor Cells Into Subjects With Transverse Myelitis
This study is a non-randomized, open-label, partially blinded, sequential cohort, dose-escalation study designed to obtain preliminary data on the safety, tolerability, and early activity of Q-Cells® transplantation in subjects with Transverse Myelitis. For each of the dose levels, transplantation of Q-Cells® unilaterally into spinal cord demyelinated lesions will be evaluated. Subjects will be blinded to side of treatment. Idiopathic Transverse Myelitis is a monophasic disorder characterized predominantly by demyelination. Patients are left with disability from damage to ascending and descending white matter tracts. Q-Cells® are comprised of glial progenitor cells.It is postulated that the Q-Cells® glial progeny (healthy astrocytes and oligodendrocytes) will integrate into the spinal cord lesion site and remyelinate demyelinated axons as well as provide trophic support for damaged axons. Therefore, Q-Cells® have the potential to repair damage that has occurred and could be clinically useful for patients with disability caused by TM. The study is planned to enroll up to 9 subjects. Each subject will be followed for 9 months after transplantation of Q-Cells®. Each subject will receive a single time point administration of Q-Cells®: with transplantation foci targeted to posterior columns in the spinal cord (all transplantation foci below C7) on one side. Study participation consists of Screening, Pre-operative/Treatment, and Post-treatment study periods that will generally last from 9 to 12 months in total. The study data will be assessed for safety and activity until the last subject has completed the 9-month study visit. Following completion of the 9-month follow-up period, subjects who consent will continue to be followed for safety and activity in a separate long-term follow-up protocol.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Taylor.Hinojo@UTSouthwestern.edu
Benjamin Greenberg
105091
All
18 Years to 70 Years old
Phase 1/Phase 2
NCT03887273
STU 052017-076
Inclusion Criteria:
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to collect and use protected health information (PHI) in accordance with national and local subject privacy regulations.
• Live within reasonable travel distance to center or have reliable mechanism to travel to the center.
• Have a caregiver willing/able to assist in the transportation and care required by study participation.
• Subject is 18 - 70 years of age (inclusive) on day of Screening Visit.
• Subject is diagnosed with idiopathic TM within the past 120 months in accord with the Transverse Myelitis Consortium Working Group (2002).
• Subject has a MRI with a single focus of T2 hyperintensity that is 4 to 10 cm in length if no post contrast enhancement seen, or a single focus T1 post contrast enhancing lesion of 4 to 10 cm, with its most rostral extent at or below C8 myotome/dermatome level.
• Subject has negative NMO IgG (anti-AQP4) test at two separate time points, separated by at least 6 months.
• Subject has brain MRI not consistent with multiple sclerosis or other autoimmune or demyelinating disease.
• Subject is more than 12 months from TM onset.
• Subject has ASIA A categorization.
• Subject's neurological deficits related to TM have been stable for at least 3 months.
• Subject is medically able to undergo the study procedures and physically able to adhere to the visit schedule at the time of study entry.
• For women of child bearing capacity, negative pregnancy test during the Screening Period and at the Pre-Operative Visit.
• Males and females will agree to practice effective birth control during study participation and up to one year after.
Exclusion Criteria:
• Subject with causes of weakness, sensory loss and/or autonomic dysfunction other than TM have not been practically excluded.
• Subject with significant cognitive impairment, clinical dementia, or major psychiatric illness including psychosis, bipolar disease, major depression, as determined by the DSM-V.
• Subject with a diagnosis of a neurodegenerative disease (e.g., ALS, Parkinson's disease, Alzheimer's disease).
• Subject suffering with medical conditions that impair nerve or muscle function (e.g., notable peripheral neuropathy, metabolic muscle disease) or any disease or condition that would impair the subject's neuromuscular function or impair the adequate assessment of the subject's function (e.g., severe osteoarthritis).
• Subject with a clinically significant history of unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease or other medically significant illness that may render them at an unacceptable risk for surgery or that may cause them to be unable to complete the scheduled duration of the trial.
• History of spine surgery or anatomic variation incompatible with route of administration (as determined by neurosurgeon).
• Severe spinal stenosis or cord compression causing myelopathy.
• Abnormal flow voids on the surface of the spinal cord suggestive of arteriovenous malformation (AVM) or evidence of a vascular cause of a myelopathy (e.g., infarct of spinal artery).
• Any evidence of CNS malignancy or clinically significant CNS lesions as defined by imaging studies of the CNS (MRI of brain and spinal cord).
• Uncontrolled hypertension (Systolic BP>180mmHg and/or Diastolic BP >110mmHg).
• Any history of thrombotic or embolic events.
• Any poorly controlled medical conditions that, in the opinion of the site investigator and/or surgeon, increase risk of surgery to a medically unacceptable degree.
• Subjects who cannot undergo MRI examination because of any contraindication to the procedure, including the presence of a pacemaker, an implanted defibrillator or certain other implanted electronic or metallic devices, or who have been or might have been exposed to metal fragments, or any reason the subject cannot undergo an MRI routinely for the duration of the trial.
• Subject with clinically significant abnormal clinical laboratory values, as determined by the Investigator at the screening visit (Visit 1).
• Subject who is immune compromised (by therapeutic agent or disease) or who has a condition contraindicated to treatment with immunosuppression agents (e.g., tuberculosis, latent infection) as determined by history or testing. Any subject with an ongoing infection until it has been adequately treated and it is deemed to be resolved.
• Subject with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value >3.0 times the upper limit of normal at the screening visit (Visit 1).
• Subject with diabetes or HgbA1c > 6.5
• Subject with a history of alcohol or drug abuse or dependence within 1 year of screening visit (Visit 1), per DSM-V criteria.
• Subject unlikely to comply with study requirements, as determined by Investigator.
• Subject who has been exposed to any other experimental agent (off-label use or investigational) within 60 days of screening visit (Visit 1). Biologic agents may need additional time for washout and will be evaluated by the Sponsor on a case-by-case basis.
• Subject with pre-existing anti-human leukocyte antigen (HLA) class I or class II antibodies directed against the Q-Cells®, as determined by panel reactive antibody (PRA) assay.
• Allergy to study treatment or any of its constituents (e.g., chicken eggs), or allergy to any of the co-administered immunosuppressants or any of their excipients.
• Subject with any medical condition or using concomitant medication that would contraindicate the use of tacrolimus, mycophenolate mofetil, or prednisone as determined by Investigator.
• Subject has undergone stem cell transplantation (including T-cell or bone marrow transplants) at any time prior to study (within or outside the US).
• Subject with evidence of deep vein thrombosis (DVT) by venous ultrasound or any previous evidence of DVT.
• Subject has recent (1 year) or recurrent history of gastrointestinal bleeding or peptic ulcer disease or is under active treatment to prevent recurrence.
• Subject with estimated glomerular filtration rate at screening of less than 60 mL/min/1.73m2.
• Subjects with hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
• Vaccination with live virus within 6 weeks of screening.
• History or evidence of optic neuritis.
• Any reason, in the judgment of the investigator, which would make the subject inappropriate for entry into this trial.
Biological: Q-Cells
Transverse Myelitis, Brain and Nervous System
UT Southwestern
The Dallas Asthma Brain and Cognition (ABC) Study
Asthma is a chronic inflammatory airway disease that leads to episodic symptom exacerbations, which exerts a substantial burden on quality of life and can influence other health domains if not adequately controlled. Asthma prevalence rates have increased in the past decade, affecting 8.4% (25.7 million people) of the United States population. The economic costs of asthma have been estimated annually with $56 billion in the US alone. Despite progress in pharmacological treatment, overall asthma control remains unsatisfactory and treatment non-adherence is extremely high. Asthma is particularly under diagnosed and understudied in aging adults. This problem will increase in coming decades given demographic trends and will disproportionally contribute to the societal and personal economic costs associated with asthma treatment and management. In the proposed 4-year project we will evaluate, in a two-session assessment recruiting a total of 126 asthma patients and 66 healthy controls aged 40-69 years, the extent to which asthma and aging are associated with changes in cognition and brain chemistry, structure, and function.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Shuchi.Lakhanpal@UTSouthwestern.edu
Edson Brown
10878
All
40 Years to 69 Years old
N/A
NCT03794856
STU-2018-0034
Inclusion Criteria:
• For asthma patients: diagnosis of asthma (verified by a medical documentation) for at least 2 years; for healthy volunteers: no significant medical or psychiatric history.
• Ages 40 to 69 years old.
• Proficient in English.
• Education level of at least 10th grade level.
Exclusion Criteria:
• Treatment with oral corticosteroids in the previous 6 weeks, because of the potent effects of this drug on airway reactivity.
• Spirometry: Peak expiratory flow (PEF) below 60% of predicted.
• Diagnosis of vocal cord dysfunction (identified by abnormalities in spirometric flow-volume curves), clinically significant chronic obstructive pulmonary disease, or emphysema.
• Presence or history of medical or neurological disorder that may affect brain function and the physiological systems of interest (e.g. angina, myocardial infarction, congestive heart failure, transient ischemic attacks, cerebrovascular accidents, emphysema, or chronic obstructive pulmonary disease, history of seizures or head trauma, endocrine disorders or renal disease, chemotherapy or radiation presently or in the past 5 years, uncontrolled diabetes, blood pressure above 160/90 (self-reported or measured at session 1).
• Corrected vision poorer than 20/30 on Snellen Eye Chart.
• Presence or history of Schizophrenia, Psychosis, Dementia, Bipolar I, Bipolar II, PTSD or Acute Stress Disorder
• Current or recent history (within 1 year) of Substance Related Disorders, current recreational drug use (defined as past 30 days) or consuming more than 20 alcoholic drinks per week.
• Current treatment with anti-psychotics, sedatives, benzodiazepines with a half-life longer than 6 hours.
• Previous electroconvulsive therapy.
• Presence of history of orthopaedic circumstances and metallic inserts interfering with MR scanning (prior surgeries and/or implant pacemakers, pacemaker wires, artificial heart value, brain aneurysm surgery, middle ear implant, non-removable hearing aid or jewelry, braces or extensive dental work, cataract surgery or lens implant, implanted mechanical or electrical device, artificial limb or joint, foreign metallic objects in the body such as bullets, BB's, shrapnel, or metalwork fragments, pregnancy, claustrophobia, uncontrollable shaking, or inability to lie still for one hour.
• Not proficient in English.
• In the opinion of the principal investigator, participant is otherwise unsuitable for this study.
Other: Functional and Structural Magnetic Resonance Imaging (research grade), Other: Cognitive Function Testing (non-diagnostic), Other: Asthma and Psychological Questionnaires (non-diagnostic)
Asthma
Healthy participants, Asthma, Cognitive functioning, MRI
UT Southwestern; Parkland Health & Hospital System
Brain Oxygen Optimization in Severe TBI, Phase 3 (BOOST3)
BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two strategies for monitoring and treating patients with traumatic brain injury (TBI) in the intensive care unit (ICU). The study will determine the safety and efficacy of a strategy guided by treatment goals based on both intracranial pressure (ICP) and brain tissue oxygen (PbtO2) as compared to a strategy guided by treatment goals based on ICP monitoring alone. Both of these alternative strategies are used in standard care. It is unknown if one is more effective than the other. In both strategies the monitoring and goals help doctors adjust treatments including the kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. The results of this study will help doctors discover if one of these methods is more safe and effective.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Lauren.Kerich@UTSouthwestern.edu
Stephen Figueroa
95844
All
14 Years and over
N/A
NCT03754114
STU-2019-0560
Inclusion Criteria:
• Non-penetrating traumatic brain injury
• Glasgow Coma Scale (GCS) 3-8 measured off paralytics
• Glasgow Coma Scale motor score < 6 if endotracheally intubated
• Evidence of intracranial trauma on CT scan
• Able to place intracranial probes and randomize within 6 hours of arrival at enrolling hospital
• Able to place intracranial probes and randomize within 12 hours from injury
• Age greater than or equal to 14 years
Exclusion Criteria:
• Non-survivable injury
• Bilaterally absent pupillary response in the absence of paralytic medication
• Contraindication to the placement of intracranial probes
• Treatment of brain tissue oxygen values prior to randomization
• Planned use of devices which may unblind treating physicians to brain tissue hypoxia
• Systemic sepsis at screening
• Refractory hypotension
• Refractory systemic hypoxia
• PaO2/FiO2 ratio < 200
• Known pre-existing neurologic disease with confounding residual neurological deficits
• Known inability to perform activities of daily living (ADL) without assistance prior to injury
• Known active drug or alcohol dependence that, in the opinion of site investigator, would interfere with physiological response to brain tissue oxygen treatments
• Pregnancy
• Prisoner
• On EFIC Opt-Out list as indicated by a bracelet or medical alert
Other: ICP + PbtO2 guided management strategy, Other: ICP guided management strategy
Brain Injuries, Traumatic
intracranial pressure, hypoxia, brain, critical care, emergency treatment, monitoring, physiologic
UT Southwestern; Parkland Health & Hospital System
ExAblate Blood-Brain Barrier (BBB) Disruption for the Treatment of Alzheimer's Disease
The purpose of this study is to evaluate the safety and efficacy of the ExAblate Model 4000 Type 2.0 System as a tool to disrupt the blood-brain barrier (BBB) in patients with probable Alzheimer's Disease (AD).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Vida.Rhodes@UTSouthwestern.edu
Bhavya Shah
173107
All
50 Years to 85 Years old
N/A
NCT03671889
STU-2020-0931
Inclusion Criteria:
• Male or Female between 50-85 years of age
• Probable Alzheimer's Disease (AD)
• If taking concurrent Alzheimer's medication, has been on the medication for at least 2 months with a stable dose for at least 3 months
• Able to communicate sensations during the ExAblate MRgFUS procedure
• Ambulatory
Exclusion Criteria:
• MRI Findings
• Presence of unknown or MR unsafe devices anywhere in the body
• Significant cardiac disease or unstable hemodynamic status
• Relative contraindications to ultrasound contrast agent or PET amyloid tracer
• History of a bleeding disorder
• History of liver disease
• Known cerebral or systemic vasculopathy
• Significant depression and at potential risk of suicide
• Any contraindications to MRI scanning
• Any contraindication to lumbar puncture for collection of cerebral spinal fluid
• Untreated, uncontrolled sleep apnea
• History of seizure disorder or epilepsy
• Severely Impaired renal function
• Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research
• Chronic pulmonary disorders
• Positive human immunodeficiency virus (HIV)
• Known apolipoprotein E allele (ApoE4) homozygosity
Device: Blood Brain Barrier (BBB) Disruption
Alzheimer Disease, Brain and Nervous System
Alzheimer Disease, Alzheimer Syndrome, Magnetic Resonance guided Focal Ultrasound (MRgFUS), Blood-Brain Barrier, ExAblate
UT Southwestern
Neurocognitive Decline in Patients With Brain Metastases
The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Zabihullah Wardak
147951
All
18 Years and over
Phase 1/Phase 2
NCT03508752
STU 122016-064
Inclusion Criteria:
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better.
• Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study.
• Six or more metastases on diagnostic or treatment planning imaging, which include either CT Brain (with contrast) or MR Brain (with or without contrast) imaging.
• Largest tumor <= 4 cm.
• No prior SRS to the lesions which will be treated on protocol.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Prior whole brain radiotherapy
• Patients with leptomeningeal metastasis. (NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal 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, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. 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.)
• Patients with life expectancy < 4 months.
• Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Radiation: Stereotactic Radiosurgery
Brain Metastases, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System
Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (TREAT-MS)
FDA-approved multiple sclerosis (MS) disease-modifying therapies (DMTs) target the relapsing phase of MS but have minimal impact once the progressive phase has begun. It is unclear if, in the relapsing phase, there is an advantage of early aggressive therapy with respect to preventing long-term disability. The infectious risks and other complications associated with higher-efficacy treatments highlight the need to quantify their effectiveness in preventing disability. The TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial is a pragmatic, randomized controlled trial that has two primary aims: 1) to evaluate, jointly and independently among patients deemed at higher risk vs. lower risk for disability accumulation, whether an "early aggressive" therapy approach, versus starting with a traditional, first-line therapy, influences the intermediate-term risk of disability, and 2) to evaluate if, among patients deemed at lower risk for disability who start on first-line MS therapies but experience breakthrough disease, those who switch to a higher-efficacy versus a new first-line therapy have different intermediate-term risk of disability.
Call 214-648-5005
studyfinder@utsouthwestern.edu, mahi.patel@utsouthwestern.edu
Peter Sguigna
83433
All
18 Years to 60 Years old
N/A
NCT03500328
STU-2021-0256
Inclusion Criteria:
• Aged 18-60 years
• Meets 2017 McDonald criteria for relapsing-remitting MS [patients with clinically isolated syndrome (CIS) are not eligible]
• Must be EITHER John Cunningham (JC) virus antibody negative or low positive (index antibody titer <0.9), OR negative for: Hepatitis B and C, tuberculosis
• HIV negative
• No chemotherapy in past year; if patient has prior history of chemotherapy or malignancy, documentation in chart explaining why potential risks of higher-efficacy therapy are justified
Exclusion Criteria:
• Prior treatment with rituximab, ocrelizumab, ofatumumab, alemtuzumab, mitoxantrone or cladribine
• Prior treatment with any other MS DMT for more than 6 months
• Prior treatment with experimental aggressive therapies (e.g., T-cell vaccine, total lymphoid radiation, stem cells)
• Treatment with teriflunomide within past 2 years (even for ≤ 6 months), unless rapid wash out done (i.e., with cholestyramine or activated charcoal)
• Treatment in the past 6 months with any MS DMT
• Prior treatment with any other investigational immune-modulating /suppressing drug for MS not listed above
• Pregnant or breast-feeding
• Women of child-bearing age who are planning or strongly considering conception during the study time frame
Other: Natalizumab, Alemtuzumab, Ocrelizumab, Rituximab, Cladribine, Ofatumumab, Ublituximab-xiiy, Other: Glatiramer acetate, Interferons (intramuscular, subcutaneous, pegylated) Teriflunomide, Fumarates (dimethyl, diroximel, monomethyl) Fingolimod, Siponimod, Ozanimod, Ponesimod
Multiple Sclerosis, Relapsing-Remitting, Brain and Nervous System
UT Southwestern
Dystonia Genotype-Phenotype Correlation
The purpose of this study is to (1) investigate the effect of known dystonia-causing mutations on brain structure and function, to (2) identify structural brain changes that differ between clinical phenotypes of dystonia, and to (3) collect DNA, detailed family history, and clinical phenotypes from patients with idiopathic dystonia with the goal of identifying new dystonia-related genes. Investigators will be recruiting both healthy control subjects and subjects with any form of dystonia. For this study there will be a maximum of two study visit involving a clinical assessment, collection of medical and family history, task training session, an MRI using the learned tasks, and finally a blood draw for genetic analysis. In total, these visits will take 3-5 hours. If the dystonia subjects receive botulinum toxin injections for treatment, the participants and their matched controls will be asked to come for a second visit.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Boudreau@UTSouthwestern.edu
Jeffrey Waugh
40638
All
11 Years and over
NCT03428009
STU 122017-069
General Exclusion (both Dystonia and Control groups):
• Metal in any part of the body (including metal injury to the eye) OR carrying a medical device incompatible with MRI (e.g., metal implants such as surgical clips or pacemakers) OR positive screening per UTSW MRI screening form
• Claustrophobia
• Non-fluent English
• Weight incompatible with MRI safety
• History of head trauma with neurological sequelae, including multiple concussions and/or history of stroke
• Pregnancy
• Serious medical illness or history of serious medical illness, including cancer that was treated with radiation or chemotherapy, heart attack, or a known history of HIV-1 + status
• Subjects with Hepatitis C (by Hepatitis C+ titer)
• Subjects with insulin dependent diabetes mellitus (IDDM)
• Severe respiratory compromise
• In the opinion of the investigator, not able to safely participate in this study
• Dystonia group Previous diagnosis of dystonia which include but is not limited to:
• cervical dystonia (50 subjects)
• blepharospasm (25 subjects)
• limb dystonia (50 subjects)
• spasmodic dysphonia (25 subjects)
• segmental dystonia
• multi-focal dystonia
• Any childhood-onset dystonia (25 subjects) Age > 11 years
• Control group: No prior dystonia diagnosis (175 subjects) Age > 11 years
• Dystonia group Prior history of or concurrent neurological or psychiatric diagnosis - depression and/or anxiety accepted Current use of non-dystonia neuroactive medications
• SSRI/medication for depression and/or anxiety accepted Current use of cervical brace designed for dystonia treatment Prior structural brain injury Control group: History of or current neurological or psychiatric diagnosis - depression and/or anxiety accepted, but must not be in active phase Current use of any neuroactive medication, SSRI/medication for depression and/or anxiety accepted
• Metal in any part of the body (including metal injury to the eye) OR carrying a medical device incompatible with MRI (e.g., metal implants such as surgical clips or pacemakers) OR positive screening per UTSW MRI screening form
• Claustrophobia
• Non-fluent English
• Weight incompatible with MRI safety
• History of head trauma with neurological sequelae, including multiple concussions and/or history of stroke
• Pregnancy
• Serious medical illness or history of serious medical illness, including cancer that was treated with radiation or chemotherapy, heart attack, or a known history of HIV-1 + status
• Subjects with Hepatitis C (by Hepatitis C+ titer)
• Subjects with insulin dependent diabetes mellitus (IDDM)
• Severe respiratory compromise
• In the opinion of the investigator, not able to safely participate in this study
Inclusion Criteria:
• Dystonia group Previous diagnosis of dystonia which include but is not limited to:
• cervical dystonia (50 subjects)
• blepharospasm (25 subjects)
• limb dystonia (50 subjects)
• spasmodic dysphonia (25 subjects)
• segmental dystonia
• multi-focal dystonia
• Any childhood-onset dystonia (25 subjects) Age > 11 years
• Control group: No prior dystonia diagnosis (175 subjects) Age > 11 years
Exclusion Criteria:
• Dystonia group Prior history of or concurrent neurological or psychiatric diagnosis - depression and/or anxiety accepted Current use of non-dystonia neuroactive medications
• SSRI/medication for depression and/or anxiety accepted Current use of cervical brace designed for dystonia treatment Prior structural brain injury Control group: History of or current neurological or psychiatric diagnosis - depression and/or anxiety accepted, but must not be in active phase Current use of any neuroactive medication, SSRI/medication for depression and/or anxiety accepted
Other: Magnetic Resonance Imaging
Dystonia, Dystonia, Idiopathic, Dystonia, Primary, Dystonia, Secondary, Dystonia, Familial, Dystonia Disorder, Dystonias, Sporadic, Dystonia, Orofacial, Dystonia Lenticularis, Dystonia, Paroxysmal, Dystonia 6, Dystonia 5, Dystonia 8, Dystonia 9, Dystonia 19, Dystonia 10, Dystonia 11, Dystonia 20, Dystonia 12, Dystonia, Focal, Dystonia of Head, Dystonia, Diurnal
Dystonia, Control, Magnetic Resonance Imagine, Genotype, Phenotype
UT Southwestern; Children’s Health