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Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Patients With Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial
The dose escalation phase of this trial identifies the safety, side effects and best dose of ceralasertib (AZD6738) when given in combination with trastuzumab deruxtecan (DS-8201a) in treating patients with solid tumors that have a change (mutation) in the HER2 gene or protein and have spread to other places in the body (advanced). The dose expansion phase (phase Ib) of this trial compares how colorectal and gastroesophageal cancers with HER2 mutation respond to treatment with a combination of ceralasertib and trastuzumab deruxtecan versus trastuzumab deruxtecan alone. Ceralasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Ceralasertib and trastuzumab deruxtecan may be safe, tolerable and effective in treating patients with advanced solid tumors expressing the HER2 protein or gene.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
ALL
18 Years and over
PHASE1
NCT04704661
STU-2023-0128
Inclusion Criteria:
* DOSE-ESCALATION PHASE: Must have histologically confirmed advanced solid tumor including but not restricted to breast cancer, gastric or gastroesophageal cancer, colon cancer, endometrial cancer, salivary gland tumors, and hepatobiliary tumors
* DOSE-EXPANSION PHASE: Must have histologically confirmed advanced/metastatic gastroesophageal cancer (cohort A) or colorectal cancer (cohort B)
* DOSE-EXPANSION PHASE: Patients must have a biopsiable lesion and provide consent for on treatment biopsy
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of AZD6738 in combination with DS-8201a in patients \< 18 years of age, children are excluded from this study
* Patients must have HER2-positive or HER2-expressing tumors determined by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory. As a rule, for HER2 immunohistochemistry (IHC) scoring system trastuzumab for gastric cancer (TOGA) criteria used for gastric/gastroesophageal junction (GEJ) cancers will be employed (Note: in escalation phase, for breast cancer patients that are included, breast cancer criteria can be used). Specific requirement of HER2 status is outlined below:
* HER2 expression (1-3+) by IHC locally and confirmed centrally OR
* HER2 expression (1-3+) by IHC tested centrally OR
* HER2 amplification based on fluorescence in situ hybridization (FISH) or next generation sequencing
* Must have received at least one line of systemic chemotherapy for either locally advanced or metastatic disease and should have either progressed on this therapy or been intolerant to this therapy
* For tumors where anti-HER2 therapy is standard of care, patients must have progressed on at least 1 line of anti-HER2 therapy if eligible. For patients where DS8201a is approved as standard of care, prior treatment with DS8201a is not allowed
* Must have unresectable, advanced/metastatic disease
* Must have at least 1 measurable lesion on CT scan per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patient without measurable but evaluable disease are allowed for dose-escalation phase
* Must be willing and able to provide an adequate archival tumor sample available to confirm HER2 status by Central Laboratory (if local testing is used for enrollment), else must be willing and able to provide an adequate archival tumor sample for HER2 testing centrally
* Must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
* Must have life expectancy of at least 3 months
* Must have left ventricular ejection fraction (LVEF) \>= 50% within 28 days before enrollment (study drug treatment) by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan
* Must have a negative pregnancy test (if female)
* Platelets \>= 100,000/mcL (within 14 days before enrollment)
* No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
* Hemoglobin \>= 9.0 g/dL (within 14 days before enrollment)
* Absolute neutrophil count \>= 1,500/mcL (within 14 days before enrollment)
* No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
* Creatinine clearance \> 45/mL/min (using the Cockcroft-Gault equation) (within 14 days before enrollment)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional upper limit of normal (ULN) (within 14 days before enrollment)
* Total bilirubin =\< 1.5 x ULN if no liver metastases or \< 3 x ULN with Gilbert's Syndrome or liver metastases at baseline (within 14 days before enrollment)
* Leukocytes \>= 3,000/mcL (within 14 days before enrollment)
* Albumin \> 2.5 g/dL (GEJ patients only) (within 14 days before enrollment)
* International normalized ratio (INR) and either partial thromboplastin time (PTT) or activated (a)PTT =\< 1.5 x ULN (within 14 days before enrollment)
* Must have adequate treatment washout period before study treatment, defined as: Major surgery (\>= 4 weeks), radiation therapy (\>= 3 weeks; in case of palliative radiation \>= 2 weeks), systemic therapy (\>= 3 weeks; in case of investigational drug use \>= 2 weeks or 5 half-lives, whichever is longer)
* Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:
* They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
* They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcl over the past 2 years, unless it was deemed related to THE CANCER AND/OR CHEMOTHERAPY-induced bone marrow suppression
* For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcl during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy
* They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of enrollment
* They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months. HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Subjects with clinically inactive brain metastases may be included. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiation therapy and study treatment
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as AZD6738 are known to be teratogenic; thus, women of child-bearing potential 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 at least 7 months (women of childbearing potential \[WOCBP\] only) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of study drug administration
* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \[FSH\] \> 40 mIU/mL and estradiol \< 40 pg/mL \[\< 147 pmol/L\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method
* Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study
* Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
* Patients with a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Patient using e-cigarettes/vaping are also excluded
* Patients with a medical history of myocardial infarction within 6 months before enrollment (study treatment), symptomatic congestive heart failure (New York Heart Association Class II to IV, corrected QT interval (QTcF) prolongation to \> 470 ms (females) or \> 450 ms (males) as corrected by Framingham's formula
* Patients with spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
* Patients with multiple primary malignancies within 2 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other curatively treated solid tumors
* Patients with a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product
* Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Patients with substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation of the subject or evaluation of the clinical study in the opinion of the investigator
* Patients with a concomitant medical condition that would increase the risk of toxicity in the opinion of the investigator
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities grade \>1) with the exception of alopecia. Subjects with chronic grade 2 toxicities may be eligible per discretion of the investigator after discussion with study principal investigator (PI) (e.g., grade 2 chemo-induced neuropathy).
* Any previous treatment with an ATR inhibitor
* Patients with any clinically apparent pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy
* Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
* Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir). The required washout period prior to starting study treatment is 2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
* Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment)
* Patients with previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
* Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable within the last 28 days as long as they are not within 1 week prior to screening assessment)
* Patients at risk of brain perfusion problems, e.g., medical history of carotid stenosis or pre-syncopal or syncopal episodes, history of transient ischemic attacks (TIAs)
* Uncontrolled hypertension (grade 2 or above) requiring clinical intervention
* Patients with relative hypotension (\< 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of \> 20 mm Hg
* Patients who have received corticosteroids (at a dose \> 10 mg prednisone/day or equivalent) for any reason within 2 weeks prior to first dose
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a. These potential risks may also apply to AZD6738
* Patients cannot be receiving chloroquine or hydroxychloroquine. Patients receiving these drugs must have a washout period of \> 14 days before enrollment/randomization PROCEDURE: Biopsy, PROCEDURE: Biospecimen Collection, DRUG: Ceralasertib, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Trastuzumab Deruxtecan
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Metastatic Breast Carcinoma, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Stage III Colon Cancer AJCC v8, Stage IV Colon Cancer AJCC v8, Advanced Endometrial Carcinoma, Clinical Stage IV Gastric Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Unresectable Malignant Solid Neoplasm, Stage III Uterine Corpus Cancer AJCC v8, Stage IV Uterine Corpus Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Gastroesophageal Junction Adenocarcinoma, Stage III Colorectal Cancer AJCC v8, Advanced Breast Carcinoma, Advanced Colon Carcinoma, Advanced Colorectal Carcinoma, Advanced Gastric Carcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Advanced Salivary Gland Carcinoma, Clinical Stage III Gastric Cancer AJCC v8, HER2-Positive Breast Carcinoma, Malignant Hepatobiliary Neoplasm, Stage III Major Salivary Gland Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IV Major Salivary Gland Cancer AJCC v8, Unresectable Colorectal Carcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma
UT Southwestern
POCUS: Hemostatic Potential and Joint Health in Patients With Severe Hemophilia A on Novel Replacement Therapies
This is a prospective, randomized control trial in which each patient will be randomly assigned to receive either extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy, which are both standard of care treatment for persons with Hemophilia A.
Call 214-648-5005
studyfinder@utsouthwestern.edu, susan.corley@childrens.com
Jessica Garcia
181672
All
up to 17 Years old
Phase 4
NCT04690322
STU-2020-1378
Inclusion Criteria:
• Subjects with moderate hemophilia A (baseline factor VIII activity 1-5%) or severe hemophilia A (baseline factor VIII activity <1%) on prophylactic standard half-life FVIII infusions OR subjects with moderate or severe hemophilia A who have not started prophylactic treatment
• Less than 18 years of age
Exclusion Criteria:
• Subjects with documented FVIII inhibitor
• Subjects with a history of ≥ 2 target joints
• Subjects with a history of synovectomy
• Currently using medications known to impact bone and mineral metabolism (e.g., bisphosphonates, corticosteroids, estrogen, testosterone, calcitonin, thyroid hormone therapy);
• Disease states known to affect bone integrity (e.g., primary hyperparathyroidism, Paget's disease, clinically significant liver disease)
Drug: Eloctate, Drug: Adynovate, Drug: Emicizumab
Hemophilia A, Bones and Joints, Other Hematopoietic, Factor VIII
Children’s Health
Ultra-fractionated Radiotherapy for Rectal Cancer
The rationale of this clinical trial is to assess the feasibility of selective non-operative management for locally advanced rectal cancer using dose-escalated ultra-fractionated short course radiation therapy interdigitated with chemotherapy. We believe delivering short course radiotherapy over a prolonged interval, at escalated doses and with concurrent chemotherapy may be feasible and allow for improved clinical response.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nina Sanford
181796
All
18 Years and over
Phase 1
NCT04677413
STU-2020-1394
Inclusion Criteria:
• At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
• Willing and able to provide written informed consent
• Pathologic diagnosis of rectal adenocarcinoma
• T3-4 and/or N+ disease per AJCC 8th edition
• No prior treatment for rectal adenocarcinoma
• Eastern Cooperative Group (ECOG) performance status of 0-2.
• Laboratory values supporting acceptable organ and marrow function within 30 days of eligibility confirmation. Defined as follows:
• WBC ≥ 3,000/mL;
• ANC WBC ≥ 1,000/mL;
• PLT ≥ 75,000/mL;
• T Bili ≤ 1.5 x upper limit of normal (ULN);
• AST/ALT ≤ 2.5 x ULN;
• Creatinine not above ULN, or creatinine clearance >50 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first dose of study therapy through 90 days after the last dose of study drugs. 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).
Exclusion Criteria:
• Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT.
• Prior RT to the pelvis.
• Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
• Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
• Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
Radiation: Ultrafractionated radiotherapy for rectal cancer
Rectal Cancer, Rectum
Rectal Cancer,T3-4 or N+
UT Southwestern; Parkland Health & Hospital System
AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED)
AZ-SWED is a parallel group, double blind, placebo control efficacy clinical trial with two separate hypotheses. The trial will compare the 5-day outcome of preschool children presenting to an Emergency Department (ED) with an acute, severe wheezing episode and treated with either once daily oral Azithromycin (12 mg/kg/day for 5 days) or placebo. The AZ-SWED researchers will make separate comparisons in children in whom specific pathogenic bacteria are isolated from nasopharyngeal swabs, and in those in whom they are not isolated. The primary outcome will be the Asthma Flare-up Diary for Young Children (ADYC), a validated instrument that caregivers will transmit electronically daily after discharge from the ED. Families will be contacted daily during the five-day treatment to collect the ADYC, and to assess compliance and complications. A randomly chosen subset of enrolled children will participate in two follow-up visits 5-8 days and 14-21 days after visit 1 to assess development of resistance to study drug and treatment response related changes in the airway microbiome.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maraki.Shebeshi@UTSouthwestern.edu
Mohamed Badawy
113377
All
18 Months to 60 Months old
Phase 3
NCT04669288
STU-2023-0897
Inclusion Criteria:
• Age 18 months to <60 months.
• The presence of expiratory wheezing as ascertained by a physician or nurse practitioner at admission to the ED.
• A Pediatric Respiratory Assessment Measurement (PRAM) score of greater than or equal to 4 at any time during the ED admission.
Exclusion Criteria:
• Presence of acute infection that requires systemic antibiotics, as determined by the physician.
• Current or previous use of systemic antibiotics within the last 2 weeks.
• Current or previous use of a steroid for wheezing within the last 2 weeks.
• Suspected foreign body induced aspiration during the last 2 weeks.
• A known systemic illness (other than allergy) including but not limited to:
• Recurrent seizures
• Gastroesophageal reflux (GER) requiring medical treatment
• Major congenital anomalies
• Physical and intellectual delay
• Cerebral palsy
• A history of chest surgery
• Tuberculosis or other chronic infections
• Primary or secondary immunodeficiency
• Gastrointestinal malformation or disease
• Cardiac disorder (except for a hemodynamically insignificant atrial septal defect (ASD), ventricular septal defect (VSD) or benign heart murmur)
• Born at less than 36 weeks estimated gestational age.
• Received oxygen for more than 5 days in the neonatal period, or received invasive mechanical ventilation.
• Significant developmental delay / failure to thrive, defined as a child plotting less than 3rd percentile.
• Any chronic lung disease.
• The study intervention poses undue risk to patient in the opinion of the treating physician
• Known sensitivity or allergy to AZ.
• Participation in the evaluation of a drug or medical device currently or within the last 30 days.
• Previous enrollment into this trial.
• Inability of the parent or guardian to speak English or Spanish.
• Positive PCR or antigen test for COVID-19 from hospital/doctor's office/testing center within the past 30 days.
Drug: Azithromycin, Drug: Placebo
Asthma, Lung/Thoracic, Wheezing
Wheezing Lower Respiratory Illness (WLRI)
Children’s Health
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
PHASE2
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
Randomized Study in Children and Adolescents With Migraine: Acute Treatment
The purpose of this study is to test the safety and efficacy of BHV-3000 versus placebo in the acute treatment of moderate or severe migraine in children and adolescents.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kiley.Poppino@UTSouthwestern.edu
Deryk Walsh
94400
ALL
6 Years to 17 Years old
PHASE3
NCT04649242
STU-2021-0107
Inclusion Criteria:
• History of migraine (with or without aura) for \> 6 months before Screening according to the IHS Classification ICHD-319 specifications for pediatric migraine. History may be verified using both medical records and recall by the participant and/or participant's parent(s)/legal representative(s).
• History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment, with attacks lasting \> 3 hours without treatment, and attacks occurring at intervals \> 24 hours.
• Prophylactic migraine medication are permitted if the dose has been stable for at least 12 weeks prior to the Baseline Visit, and the dose is not expected to change during the course of the study.
• Participants may remain on one (1) medication with possible migraine prophylactic effects, excluding CGRP antagonists \[biologic or small molecule\], during the treatment phases.
• Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is prohibited.
• Previously discontinued prophylactic migraine medication must have done so at least 90 days prior to the Screening Visit.
• Verbally distinguish between migraine and other types of headaches.
• Participants must have a weight \> 40 kg at the Screening Visit.
• Adequate venous access for blood sampling.
• Male and female participants ≥ 6 to \< 18 years of age (participants must not reach their 18th birthday during the study).
Exclusion Criteria:
• History of cluster headache or hemiplegic migraine headache.
• Confounding and clinically significant pain syndrome that may interfere with the participant's ability to participate in this study.
• Current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Participants with a lifetime history of psychosis and/or mania.
• History of suicidal behavior or major psychiatric disorder.
• Current diagnosis or history of substance abuse; positive drug test at Screening.
• History of moderate or severe head trauma or other neurological disorder (including seizure disorder) or systemic medical disease that is likely to affect central nervous system functioning.
• Recent or planned surgery, requiring general anesthesia, \<8 weeks prior to the Screening Visit.
• Participant has had gastrointestinal surgery that interferes with physiological absorption and motility (i.e., gastric bypass, duodenectomy, or gastric banding).
• Current diagnosis of viral hepatitis or a history of liver disease.
• Conditions considered clinically relevant in the context of the study such as uncontrolled hypertension (high blood pressure), diabetes, a life-threatening allergy
DRUG: Rimegepant/BHV3000, DRUG: Matching placebo
Brain and Nervous System, Pediatric Migraine
Migraine, Acute treatment, Phonophobia, Photophobia, Nausea, Pediatric, Children, Adolescent, Pediatric Migraine
Children’s Health
Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) (MOVE FSHD)
The primary goal of this proposal is to collect motor and functional outcomes specific to FSHD over time. By collecting measures specific to FSHD, this will help ensure the best level of clinical care is being provided. Also, the hope is to speed up drug development by gaining a better understanding of how having FSHD impacts motor function and other health outcomes (i.e. breathing, wheelchair use, etc.) and how big a change in motor function would be clinically meaningful to those with FSHD. Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) will have approximately 450 FSHD participants followed for a minimum of 3 years. A subset of MOVE FSHD participants, approximately 200, will participate in the MOVE+ sub-study which includes whole body MRI and muscle biopsy.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Tara.Kristof@UTSouthwestern.edu
Jaya Trivedi
46764
All
Not specified
NCT04635891
STU-2020-0726
Inclusion Criteria:
• Genetically confirmed FSHD (types 1 or 2) or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring.
Exclusion Criteria:
• Unwilling or unable to provide informed consent.
• Any other medical condition which in the opinion of the investigator would interfere with study participation.
FSHD
UT Southwestern
Polypill Strategy for Heart Failure With Reduced Ejection Fraction
Heart failure with a reduced ejection fraction (HFrEF) represents a significant public health burden in the United States, with a growing prevalence particularly among African Americans and Hispanic Americans and individuals of low socioeconomic status (SES). Although effective therapies exist, gaps in their uptake contribute substantially to the excess burden of heart failure. The "polypill" is an inexpensive once daily pill containing three agents proven to improve morbidity and mortality in heart failure and represents potential strategy for increasing the utilization of proven HF therapies. The proposed study is a pragmatic, single-center, randomized trial to test the feasibility and effectiveness of a polypill-based strategy for the treatment of HFrEF in a low-income, racially diverse population.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Neil.Keshvani@UTSouthwestern.edu
Ambarish Pandey
125045
All
18 Years and over
Early Phase 1
NCT04633005
STU-2020-1340
Inclusion Criteria:
• Adults age > = 18 years
• HF with left ventricular ejection fraction <= 40% within 3 months of screening who are not on optimal guideline directed medical therapy
• New York Heart Association class II, III, or IV symptoms
Exclusion Criteria:
• Age < 18
• Systolic blood pressure < 110 mm Hg at enrollment if not on HTN therapy.
• Systolic blood pressure <100 mm Hg at enrollment if on HTN therapy
• Serum creatinine >2.5 for men and 2.0 for women
• Serum potassium > 5.0 mEq/L
• Current need for inotropes
• Cardiac index < 2.2 L/min/m2
• History of revascularization within 30 days or plan for revascularization
• History of type 1 diabetes mellitus
• History of allergic reaction or contraindication to a beta-blocker (BB), mineralocorticoid receptor antagonist (MRA), or sodium glucose cotransporter 2 inhibitor (SGLT2i)
• Contraindication to receive any of the components of the polypill
• Pregnancy
• < 12 month expected survival
• Inability to provide written informed consent
• Persistent or permanent atrial fibrillation who may not have optimal MRI imaging
• Extreme obesity (BMI > 45 kg/m2)
• ICD/Pacemaker devices that are incompatible with MRI
Drug: Polypill, Drug: Control Rx
Heart Failure, Heart
UT Southwestern; Parkland Health & Hospital System
A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC) (VISTAS)
The purpose of this clinical research study is to learn more about the use of the study medicine, volixibat, for the treatment of pruritus (itching) associated with Primary Sclerosing Cholangitis (PSC), and to assess the possible impact on the disease progression of PSC.
Call 214-648-5005
studyfinder@utsouthwestern.edu, lakeisha.johnson@utsouthwestern.edu
Marlyn Mayo
14698
ALL
12 Years and over
PHASE2
NCT04663308
STU-2021-0116
Inclusion Criteria:
• Provide freely signed informed consent and assent (as applicable) and be willing to comply with all study visits and requirements through end of study, including the follow-up period.
• Subjects aged ≥12 years for eligible regions; otherwise ≥18 years
• Confirmed diagnosis of large duct or small duct PSC based on American Association for the Study of Liver Disease (AASLD) guidelines.
• Pruritus associated with PSC as assessed by Adult ItchRO.
• Ursodeoxycholic acid (UDCA) and anti-pruritic medication use will be allowed if meeting additional criteria.
• Concomitant Inflammatory Bowel Disease (IBD) is allowed if meeting additional criteria.
Exclusion Criteria:
• Pruritus associated with an etiology other than PSC
• Evidence or clinical suspicion of decompensated cirrhosis, or a history of decompensation events
• History of ileostomy or small bowel surgery/resection or other surgeries that may have disrupted the enterohepatic circulation
• Evidence, history, or suspicion of other liver disease; PSC patients with AIH are not excluded.
• Bile duct stent or percutaneous bile duct drain placement, or balloon dilatation procedure of a stricture within 12 weeks of Screening
• Exceeding pre-defined biochemical values for alanine aminotransferase/aspartate aminotransferase (ALT/AST), estimated glomerular filtration rate (eGFR),serum creatinine (sCr), platelet count, international normalized ratio (INR) and total bilirubin
• History of liver transplantation
DRUG: Volixibat, DRUG: Placebo
Liver, Primary Sclerosing Cholangitis
Pruritus, PSC, Itch, Itching, Cholestasis
UT Southwestern
Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer
This phase II/III trial compares the effect of adding durvalumab to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine 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. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vitaly Margulis
49444
ALL
18 Years and over
PHASE2
NCT04628767
STU-2021-0698
Inclusion Criteria:
* STEP 1 REGISTRATION AND RANDOMIZATION
* Patients must be \>= 18 years of age
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patient must have a diagnosis of high grade upper tract urothelial carcinoma proven by biopsy within 12 weeks (84 days) prior to registration/randomization with one of the following:
* Upper urinary tract mass on cross-sectional imaging or
* Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology
* NOTE: Biopsy is standard of care (SOC) and required for enrollment to study. This is vital for best practice
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to registration/randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to registration/randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (or =\< 2.5 x ULN for patients with Gilbert's disease) (obtained =\< 14 days prior to registration/randomization)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 14 days prior to registration/randomization)
* Hemoglobin (Hgb) \>= 9 g/dL (obtained =\< 14 days prior to registration/randomization)
* NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration/randomization are eligible for this trial
* NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
* NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of registration/randomization
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patient must have a body weight of \> 30 kg
* Patient must have life expectancy of \>= 12 weeks
* Patient must have creatinine clearance \> 15 ml/min as by Crockroft-Gault formula or 24-hour creatinine clearance within 28 days prior to registration/randomization
* NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and/or hearing loss in keeping with SOC cisplatin contraindications. Patients that are cisplatin-eligible will be randomized to either Arm A or Arm B
* Patients that meet any of the following criteria will be registered and assigned to the cisplatin-ineligible Arm C if they meet other eligibility criteria:
* Creatinine clearance \> 15 ml/min and =\< 50 ml/min or hearing loss grade \>= 3, or neuropathy \>= 2, or ECOG PS 2
* Patient must have an absolute neutrophil count (ANC) \>= 1,000/mcL obtained =\< 14 days prior to registration
* Patient must have ECOG performance status 0-2
* Patients that meet the following criteria will be randomized to the cisplatin-eligible Arm A or Arm B:
* Patient must have creatinine clearance of \> 50ml/min, PS ECOG 0-1, absence of hearing loss grade \>= 3, and/or neuropathy \>= 2
* Patient must have an absolute neutrophil count (ANC) \>= 1,500/mcL obtained =\< 14 days prior to randomization
* Patient must have left ventricular ejection fraction (LVEF) \>= 50% by (either multigated acquisition scan \[MUGA\] or 2-D echocardiogram) obtained within obtained within 28 days prior to randomization
Exclusion Criteria:
* Patients must not have any component of small cell/neuroendocrine carcinoma. Other variant histologic types are permitted provided the predominant (\>= 50%) subtype is urothelial carcinoma
* Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients of childbearing potential and sexually active patients must not expect to conceive or father children, either by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment
* Patients must have no evidence of metastatic disease or clinically enlarged regional lymph nodes (\>= 1.5 cm short axis) on imaging required within 28 days prior to registration (Non-regional findings \>=1.5 cm short axis that in the opinion of the investigator are not concerning for involvement based on radiographic characteristics, chronicity, avidity on positron emission tomography (PET) or other imaging or other criteria can be eligible based on investigator discretion).
* NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness can also undergo baseline bone scans to evaluate for bone metastasis at the discretion of local provider.
* Patient must meet below criteria for prior/current malignancy history:
* Non-urothelial cancer malignancy history:
* Patient must not have another active (or within two years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =\< Gleason 3+4) on active surveillance (or watchful waiting) or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat
* NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients in whom concomitant or prior bladder/urethra predominant (\>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (\< cT1N0) are eligible regardless of time elapsed
* Urothelial cancer malignancy history:
* Patient may have a history of resectable urothelial cancer as long as patients meet one of the following:
* T0, Ta or Tis at any time
* T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy \[e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy (neoadjuvant or adjuvant, or with radiation)\]. Prior immune checkpoint inhibitor is not allowed.
* Patient with history of \>= pT4b, N+, and/or M1 is not eligible.
* NOTE: Patients in whom concomitant or prior bladder/urethra predominant (\>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only Ta or carcinoma in situ (CIS) (\< cT1 N0) are eligible regardless of time elapsed
* Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) in last three months, or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, clinically relevant liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements
* Patient must not have received prior radiation therapy to \>= 25% of the bone marrow for other diseases
* Patient must not have received prior systemic anthracycline therapy
* NOTE: Patients who have received prior intravesical chemotherapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible
* Patient must not have either history of or active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration/randomization or any history of inflammatory bowel disease (inflammatory bowel disease \[IBD\], colitis, or Crohn's disease), neuromuscular autoimmune condition, immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible
* Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of durvalumab. The following are exceptions to this criterion:
* Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g. intra-articular injection
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment
* Steroids as premedications for hypersensitivity reactions (e.g. computed tomography \[CT\] scan premedication)
* Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab, while on protocol treatment and within 30 days after the last dose of durvalumab
* Patient must not have had a major surgical procedure within 28 days prior to registration/randomization
* NOTE: Cystoscopy/ureteroscopy, stent placement or nephrostomy tube is not considered major surgery
* Patient must not have history of allogenic organ transplantation PROCEDURE: Biopsy, PROCEDURE: Biospecimen Collection, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Doxorubicin Hydrochloride, BIOLOGICAL: Durvalumab, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Therapeutic Conventional Surgery, DRUG: Vinblastine Sulfate
Renal Pelvis and Ureter Urothelial Carcinoma
UT Southwestern; Parkland Health & Hospital System
Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome (EPCORE™ CLL-1)
The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will either be studied as: - Monotherapy, or - Combination therapy: - epcoritamab + venetoclax - epcoritamab + lenalidomide - epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone). The study includes patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)/small lymphocytic lymphoma (SLL) and patients with Richter's Syndrome (RS). Study participants with R/R CLL/SLL are treated either with epcoritamab as monotherapy or epcoritamab + venetoclax. Study participants with RS are treated either with epcoritamab as monotherapy or epcoritamab + lenalidomide or epcoritamab + R-CHOP. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Patients with RS are only included in the expansion phase.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
180091
All
18 Years and over
Phase 1/Phase 2
NCT04623541
STU-2020-1263
Key Inclusion Criteria
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Evidence of CD20 positivity in a sample representative of the disease at Screening.
• Acceptable hematology parameters and organ function based on baseline bloodwork.
• For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
• For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
• For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
• For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
• For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
• Life expectancy >3 months on standard of care (SOC).
• For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
• For RS - lenalidomide combination therapy arm
• Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
• Eligible for treatment with lenalidomide.
• Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
• For RS - R-CHOP combination Therapy Arm -
• Eligible for treatment with R-CHOP.
• For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy. Key Exclusion Criteria
• Received prior treatment with a CD3×CD20 bispecific antibody.
• Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
• Received (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
• Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• Received vaccination with live vaccines within 28 days.
• Clinically significant cardiac disease.
• Known current malignancy other than inclusion diagnosis.
• Has had major surgery within 4 weeks.
• Active hepatitis B virus or active hepatitis C.
• Known history of HIV.
• For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
• Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
• For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
• RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Evidence of CD20 positivity in a sample representative of the disease at Screening.
• Acceptable hematology parameters and organ function based on baseline bloodwork.
• For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
• For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
• For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
• For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
• For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
• Life expectancy >3 months on standard of care (SOC).
• For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
• For RS - lenalidomide combination therapy arm
• Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
• Eligible for treatment with lenalidomide.
• Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
• For RS - R-CHOP combination Therapy Arm -
• Eligible for treatment with R-CHOP.
• For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy. Key Exclusion Criteria
• Received prior treatment with a CD3×CD20 bispecific antibody.
• Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
• Received (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
• Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• Received vaccination with live vaccines within 28 days.
• Clinically significant cardiac disease.
• Known current malignancy other than inclusion diagnosis.
• Has had major surgery within 4 weeks.
• Active hepatitis B virus or active hepatitis C.
• Known history of HIV.
• For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
• Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
• For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
• RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Biological: Epcoritamab, Biological: Epcoritamab, Drug: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, Drug: Venetoclax, Biological: Epcoritamab, Drug: Lenalidomide
Small Lymphocytic Lymphoma, Lymphoid Leukemia, Relapsed/Refractory Chronic Lymphocytic Leukemia, Richter's Syndrome
DuoBody®, Bispecific antibodies, Anti-CD3, Anti-CD20
UT Southwestern
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
Single Cell Immune and Non-immune Correlates of Response to Neoadjuvant Abemaciclib
The purpose of this study is to better understand how the immune system plays a role in fighting breast cancer and specifically research if the immune system response against breast cancer can be improved with endocrine therapy and cyclin dependent kinase inhibitor therapy in patients with hormone receptor positive breast cancer. This will be studied by collecting tumor tissue and blood samples before and after 2 weeks of study treatment with commonly used endocrine therapy and cyclin dependent kinase inhibitor therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sangeetha Reddy
188773
Female
18 Years and over
Phase 2
NCT04614194
STU-2020-1043
INCLUSION CRITERIA:
• Clinical stage operable stage I, II, or III invasive mammary carcinoma, which is estrogen receptor or progesterone receptor positive by immunohistochemistry and HER2 negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.
• Have post-menopausal status, as defined by any of the following: Subjects at least 55 years of age OR Subjects under 55 years of age and amenorrheic for at least 12 months OR follicule stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels ≤ 40 pg/mL (140 pmol/L) or in postmenopausal ranges per local or institutional reference ranges.
• Breast tumor ≥1cm in diameter by either physical exam or ultrasound and suitable for pre and post-treatment tissue sampling.
• Meet either of 2 following criteria, for which neoadjuvant endocrine therapy for 2 weeks is deemed suitable: 1) disease that is planned for surgery as initial therapy, in which 2 weeks of neoadjuvant endocrine therapy is deemed suitable, 2) Disease for which neoadjuvant systemic therapy (either chemotherapy or endocrine therapy) may be planned, in which 2 weeks of neoadjuvant endocrine therapy prior to start of systemic therapy is deemed suitable.
• At least 18 years of age
• Performance status ECOG ≤ 2
• Have adequate organ function (ANC ≥1,500/mcL, Platelets ≥100,000/mcL, Hemoglobin ≥8 g/dL, Total bilirubin ≤1.5 × upper limit of normal, ALT and AST ≤3 × upper limit of normal, Creatinine clearance >30 mL/minute
• The patient is able to swallow oral medications
• Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer.
• Women may have been taking tamoxifen or raloxifene as a preventive agent prior to study entry but must have discontinued the drug for at least 28 days prior to study enrollment.
• Subjects have ended hormone replacement therapy at least 7 days prior to receiving the first dose of randomized therapy.
• Ability to understand and the willingness to sign a written informed consent.
• A female of childbearing potential, must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib and agree to use a highly effective contraception method during the treatment period and for 3 weeks following the last dose of abemaciclib. These criteria should not apply to most or all patients on the trial given the inclusion criteria is for post-menopausal patients only who should not be of childbearing potential. Note: Contraceptive methods may include an intrauterine device [IUD] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation. EXCLUSION CRITERIA:
• Active metastatic breast cancer, inflammatory breast cancer, or locally recurrent breast cancer.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
• Females who are pregnant, lactating, or premenopausal.
• Severe uncontrolled malabsorption condition or disease (i.e. grade 2 or higher diarrhea, severe malnutrition, short gut syndrome).
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Chemotherapy, radiotherapy, or any other cancer therapy for current diagnosis of breast cancer.
• Subjects may not have received or be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Clinical stage operable stage I, II, or III invasive mammary carcinoma, which is estrogen receptor or progesterone receptor positive by immunohistochemistry and HER2 negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.
• Have post-menopausal status, as defined by any of the following: Subjects at least 55 years of age OR Subjects under 55 years of age and amenorrheic for at least 12 months OR follicule stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels ≤ 40 pg/mL (140 pmol/L) or in postmenopausal ranges per local or institutional reference ranges.
• Breast tumor ≥1cm in diameter by either physical exam or ultrasound and suitable for pre and post-treatment tissue sampling.
• Meet either of 2 following criteria, for which neoadjuvant endocrine therapy for 2 weeks is deemed suitable: 1) disease that is planned for surgery as initial therapy, in which 2 weeks of neoadjuvant endocrine therapy is deemed suitable, 2) Disease for which neoadjuvant systemic therapy (either chemotherapy or endocrine therapy) may be planned, in which 2 weeks of neoadjuvant endocrine therapy prior to start of systemic therapy is deemed suitable.
• At least 18 years of age
• Performance status ECOG ≤ 2
• Have adequate organ function (ANC ≥1,500/mcL, Platelets ≥100,000/mcL, Hemoglobin ≥8 g/dL, Total bilirubin ≤1.5 × upper limit of normal, ALT and AST ≤3 × upper limit of normal, Creatinine clearance >30 mL/minute
• The patient is able to swallow oral medications
• Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer.
• Women may have been taking tamoxifen or raloxifene as a preventive agent prior to study entry but must have discontinued the drug for at least 28 days prior to study enrollment.
• Subjects have ended hormone replacement therapy at least 7 days prior to receiving the first dose of randomized therapy.
• Ability to understand and the willingness to sign a written informed consent.
• A female of childbearing potential, must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib and agree to use a highly effective contraception method during the treatment period and for 3 weeks following the last dose of abemaciclib. These criteria should not apply to most or all patients on the trial given the inclusion criteria is for post-menopausal patients only who should not be of childbearing potential. Note: Contraceptive methods may include an intrauterine device [IUD] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation. EXCLUSION CRITERIA:
• Active metastatic breast cancer, inflammatory breast cancer, or locally recurrent breast cancer.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
• Females who are pregnant, lactating, or premenopausal.
• Severe uncontrolled malabsorption condition or disease (i.e. grade 2 or higher diarrhea, severe malnutrition, short gut syndrome).
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Chemotherapy, radiotherapy, or any other cancer therapy for current diagnosis of breast cancer.
• Subjects may not have received or be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
Drug: Letrozole, Drug: Abemaciclib
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma
This phase I trial tests the safety, side effects, best dose and effectiveness of lenalidomide when added to nivolumab and the usual drugs (rituximab and methotrexate) in patients with primary central nervous system (CNS) lymphoma. Lenalidomide may stop or slow primary CNS lymphoma by blocking the growth of new blood vessels necessary for tumor growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Methotrexate is frequently combined with other chemotherapy agents to improve response. This study may help increase the understanding of lenalidomide and nivolumab use in primary CNS lymphoma treatment. In addition, it may help researchers see whether the control of CNS lymphoma can be extended by using these study drugs as maintenance (prolonged therapy) after control is achieved with the initial chemotherapy regimen (induction).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Praveen Ramakrishnan Geethakumari
171719
ALL
18 Years and over
PHASE1
NCT04609046
STU-2021-0822
Inclusion Criteria:
* Histologically proven primary CNS diffuse large b-cell lymphoma confirmed by one of the following:
* Brain biopsy or resection
* Cerebrospinal fluid
* Vitreous fluid
* No prior organ transplantation to exclude post-transplant lymphoproliferative disorders
* No prior chemotherapy or radiation therapy for lymphoma
* No prior allogeneic stem cell transplantation
* Use of systemic corticosteroids (dexamethasone up to 24 mg/day or equivalent) for disease control or improvement of performance status to be tapered as fast as clinically safe after initiation of therapy is permissible
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, female of childbearing potential (FCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) =\< 7 days prior to registration
* Age \>= 18 years
* Karnofsky performance scale (KPS) \>= 40 (\>= 50 for patients older than 60 unless related to lymphoma on investigator's opinion)
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Calculated creatinine clearance \>= 50 mL/min by Cockcroft-Gault formula
* Total Bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
* No evidence of non-Hodgkin's lymphoma (NHL) outside CNS
* No prior history of NHL
* No history of autoimmune disorder. Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as Systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
* Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (except short course of systemic corticosteroids for disease control or improvement of performance status or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
* Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study
* No prior or concurrent malignancies with exception of surgically cured carcinoma in situ (CIS) of the uterus, carcinoma of the skin without evidence of disease for \>= 5 years
* No concurrent malignancy requiring active therapy
* No untreated hepatitis C virus (HCV) infection with detectable HCV viral load
* No untreated chronic hepatitis B virus (HBV) infection with detectable HBV viral load
* No untreated human immunodeficiency virus (HIV) infection or with detectable viral load or with CD4+T-cell count of less than 500/mm\^3
* No history of HIV infection and evidence of Epstein Barr virus (EBV)-related primary central nervous system lymphoma (PCNSL)
* Inability to tolerate anticoagulation with acetylsalicylic acid, warfarin, or direct oral anticoagulants
* No other investigational agent
* No history of severe hypersensitivity reaction to any monoclonal antibody
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to or other agents used in study
* Sulfonamide drugs, trimethoprim, salicylates, nonsteroidal anti-inflammatory drugs, penicillin, vitamin C, ciprofloxacin, and proton pump inhibitors should be held at least 48 hours prior to methotrexate administration PROCEDURE: Bone Marrow Aspiration and Biopsy, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography, DRUG: Lenalidomide, PROCEDURE: Lumbar Puncture, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Rituximab, PROCEDURE: Ultrasound Imaging
Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System
UT Southwestern
Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL) (EPCORE™ NHL-2)
The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating subjects with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied. Trial details include: * The total trial duration will be up to 6 years. * The treatment duration for each participant depends upon which arm of treatment they are assigned to receive, but will be no more than 3 years. * The visit frequency for each participant depends upon which arm of treatment they are assigned to receive, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks. * All participants will receive active drug; no one will be given placebo. Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned. Participants who receive standard treatments will have IV infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned. Arm 9 (follicular lymphoma (FL)) is still open for enrolment of new patients, while the other arms have closed their recruitment.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
180091
ALL
18 Years and over
PHASE1
NCT04663347
STU-2021-0153
Key Inclusion Criteria
• Measurable disease defined as ≥1 measurable nodal lesion (long axis \>1.5 cm and short axis \>1.0 cm) or ≥1 measurable extra-nodal lesion (long axis \>1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
• Acceptable organ function at screening
• CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
• If of childbearing potential subject must practicing a highly effective method of birth control
• A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control Arm 1: * Newly diagnosed DLBCL * DLBCL, not otherwise specified (NOS) * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 2: R/R FL Arm 3: Newly diagnosed, previously untreated FL grade 1-3A Arm 4: * Documented R/R DLBCL and eligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 5: * Documented R/R DLBCL and ineligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 6: Newly diagnosed, previously untreated FL grade 1-3A Arm 7: * FL Grade 1-3A * If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment. Arm 8: * Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline * T-cell/histiocyte rich DLBCL * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 9: * R/R FL * Progressed within 24 months of initiating first-line treatment Arm 10: * Documented R/R DLBCL and eligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Key Exclusion Criteria
• Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
• Any prior treatment with a bispecific antibody targeting CD3 and CD20.
• Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
• Clinically significant cardiovascular disease
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
• Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• Known history of seropositivity of human immunodeficiency virus (HIV)
• Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
• Neuropathy \> grade 1
• Receiving immunostimulatory agent
• Prior allogeneic HSCT
• Current seizure disorder requiring anti-epileptic therapy NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
• Measurable disease defined as ≥1 measurable nodal lesion (long axis \>1.5 cm and short axis \>1.0 cm) or ≥1 measurable extra-nodal lesion (long axis \>1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
• Acceptable organ function at screening
• CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
• If of childbearing potential subject must practicing a highly effective method of birth control
• A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control Arm 1: * Newly diagnosed DLBCL * DLBCL, not otherwise specified (NOS) * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 2: R/R FL Arm 3: Newly diagnosed, previously untreated FL grade 1-3A Arm 4: * Documented R/R DLBCL and eligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 5: * Documented R/R DLBCL and ineligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 6: Newly diagnosed, previously untreated FL grade 1-3A Arm 7: * FL Grade 1-3A * If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment. Arm 8: * Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline * T-cell/histiocyte rich DLBCL * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 9: * R/R FL * Progressed within 24 months of initiating first-line treatment Arm 10: * Documented R/R DLBCL and eligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Key Exclusion Criteria
• Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
• Any prior treatment with a bispecific antibody targeting CD3 and CD20.
• Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
• Clinically significant cardiovascular disease
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
• Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• Known history of seropositivity of human immunodeficiency virus (HIV)
• Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
• Neuropathy \> grade 1
• Receiving immunostimulatory agent
• Prior allogeneic HSCT
• Current seizure disorder requiring anti-epileptic therapy NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
DRUG: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, DRUG: rituximab and lenalidomide, DRUG: rituximab and bendamustine, DRUG: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin, DRUG: gemcitabine and oxaliplatin, BIOLOGICAL: Epcoritamab, DRUG: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone, DRUG: Lenalidomide, DRUG: rituximab, ifosfamide, carboplatin, and etoposide phosphate, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab
Diffuse Large B-Cell Lymphoma, Follicular Lymphoma
DuoBody®, monoclonal antibodies, anti-CD3, anti-CD20
UT Southwestern
'Re-Priming' RT After Incomplete Response to CAR-T in R/R NHL
This is a single-arm open-label phase I/II trial studying the safety and efficacy of focal 're-priming' radiation therapy (RT) to FDG-avid residual sites of disease in relapsed/refractory non-Hodgkin lymphoma (R/R NHL) patients with incomplete response (IR) to CAR T-cell therapy (CAR-T) by day 30 post-CAR-T PET/CT. We hypothesize that focal 're-priming' RT will be safe (phase I) and improve conversion to metabolic complete response (CR) by day 90 post-CAR-T PET/CT from 29% (historical control) to 58% (phase II).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kiran Kumar
181795
All
18 Years and over
Phase 1/Phase 2
NCT04601831
STU-2020-1106
Inclusion Criteria:
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
• Biopsy-proven histological high-grade non-Hodgkin lymphoma, such as diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma.
• Prior treatment with any CD19-directed CAR T-cell therapy, such as tisagenlecleucel (tisa-cel, Kymriah), axicabtagene ciloleucel (axi-cel, Yescarta), or lisocabtagene maraleucel (liso-cel).
• Incomplete response noted on day 30 PET post-CAR-T, defined as not achieving CR per Lugano 2014 classification
• Ability to understand and the willingness to sign a written informed consent
• All men, as well as women of child-bearing potential 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.
• 1 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).
Exclusion Criteria:
• Prior "definitive" radiation therapy (40-50 Gy EQD2 with an α/β of 10) to one or more sites of incomplete response as noted on day 30 post-CAR-T PET/CT scan within the past one year. Prior "palliative" radiation therapy (<40 Gy EQD2) permissible at discretion of treating physician.
• Intracranial site of incomplete response as noted on day 30 post-CAR-T PET/CT scan or any active central nervous system involvement by malignancy.
• Active grade 3 or higher CRS or neurotoxicity related to CAR-T.
• Patients with prior history of auto-immune disease or other contraindication to RT.
• Patients with life expectancy < 3 months.
• Psychiatric illness/social situations that 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.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
Radiation: Focal radiation therapy (RT)
Non-hodgkin Lymphoma, Non-Hodgkins Lymphoma
CAR-T, Radiation therapy, NHL, DLBCL, RT
UT Southwestern
Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents
This project aims to examine the efficacy of ketamine, a rapidly acting medication shown to decrease suicidality in adults in as short as hours or days, as opposed to weeks. The study design is a double-blind, randomized, active-control trial of adolescents (ages 13-18 years) with recent suicidal behaviors (suicide attempt or increased suicidal ideation). All participants must be receiving standard of care treatment which may range broadly from both outpatient and inpatient programs which include clinically indicated psychosocial and/or psychopharmacological treatments. Ketamine/midazolam treatment will occur twice weekly during the first two weeks of the study, followed by weekly assessments through week 12.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Zachary.Brown@UTSouthwestern.edu
Madhukar Trivedi
17410
All
13 Years to 18 Years old
Phase 3
NCT04592809
STU-2020-0973
Inclusion Criteria
Study participants must:
• Be adolescents (aged 13-18 years);
• Have had a recent suicidal event (suicide attempt or significant suicidal ideation with a plan or intent warranting emergency evaluation or inpatient hospitalization within the past 90 days);
• Receiving standard of care treatment that includes clinically indicated psychosocial and/or psychopharmacological treatment;
• Have a current primary diagnosis of a depressive disorder based on the MINI-KID (other psychiatric disorders are acceptable, but must not be primary);
• Both participants and their designated caregiver must be able to complete assessments in English, as the rating scales vital to study efficacy and safety evaluations have not been validated in Spanish. (NOTE: Most potential participants ages 13 to 18 years old, as well as most of their parents, have a good working knowledge of English);
• Use effective method of contraception during and for 90 days following the end of treatment for female and male participants. Recommended methods of birth control are namely, consistent use of an approved hormonal birth control (pill/patches, rings), an intrauterine device (IUD), contraceptive injection, double barrier methods, sexual abstinence, or sterilization; Exclusion Criteria Study participants must not:
• Have a psychotic disorder, such as lifetime schizophrenia, or a pervasive or intellectual developmental disorder requiring substantial or very substantial support;
• Have current mania, hypomania, mixed episode, or obsessive-compulsive disorder;
• Have a primary diagnosis other than a depressive disorder;
• Have moderate to severe alcohol or substance use disorder within the past six months (based on MINI-KID); If there is a positive urine drug screen at screening, the urine drug screen will be repeated at each infusion visit. Positive urine drug screen will be reviewed by study physician and infusion will proceed as long as no safety risk was identified;
• If female, be pregnant, lactating, or nursing; Women of childbearing potential must have a negative urine pregnancy test prior to all infusions;
• Have unstable medical conditions (stable for less than 3 months) or with clinically significant laboratory values or an electrocardiogram (ECG) that would pose significant risk;
• Be at serious suicidal risk that cannot be managed in the outpatient setting;
• Have prior treatment for depression with or contraindications to ketamine, esketamine, or, midazolam;
• Treatment with medications that may alter pharmacokinetics of ketamine, including moderate-to-strong inhibitors or inducers of CYP3A4 and CYP2B6, is exclusionary. Regarding pharmacodynamic interactions, medications that may increase heart rate or blood pressure such as the ADHD stimulant medications will be permitted with last dose at least 24 hours prior to infusion. All concomitant medications will be evaluated by the study physician to determine if the type and dose of concomitant medication requires discontinuation and will be excluded if the concomitant medication could substantially increase the risk of study infusion. A complete list of medications that are Not Allowed is available in Appendix D of the protocol. The study team will not ask the participant to discontinue any treatment (except for not taking ADHD medications for 24 hours before study treatment) just for the sake of taking part in this study;
• Weigh >120 kilograms at baseline. If participants are enrolled but exceed 120 kilograms at any time during the treatment period, they will be removed from the treatment portion of the study.
• Be adolescents (aged 13-18 years);
• Have had a recent suicidal event (suicide attempt or significant suicidal ideation with a plan or intent warranting emergency evaluation or inpatient hospitalization within the past 90 days);
• Receiving standard of care treatment that includes clinically indicated psychosocial and/or psychopharmacological treatment;
• Have a current primary diagnosis of a depressive disorder based on the MINI-KID (other psychiatric disorders are acceptable, but must not be primary);
• Both participants and their designated caregiver must be able to complete assessments in English, as the rating scales vital to study efficacy and safety evaluations have not been validated in Spanish. (NOTE: Most potential participants ages 13 to 18 years old, as well as most of their parents, have a good working knowledge of English);
• Use effective method of contraception during and for 90 days following the end of treatment for female and male participants. Recommended methods of birth control are namely, consistent use of an approved hormonal birth control (pill/patches, rings), an intrauterine device (IUD), contraceptive injection, double barrier methods, sexual abstinence, or sterilization; Exclusion Criteria Study participants must not:
• Have a psychotic disorder, such as lifetime schizophrenia, or a pervasive or intellectual developmental disorder requiring substantial or very substantial support;
• Have current mania, hypomania, mixed episode, or obsessive-compulsive disorder;
• Have a primary diagnosis other than a depressive disorder;
• Have moderate to severe alcohol or substance use disorder within the past six months (based on MINI-KID); If there is a positive urine drug screen at screening, the urine drug screen will be repeated at each infusion visit. Positive urine drug screen will be reviewed by study physician and infusion will proceed as long as no safety risk was identified;
• If female, be pregnant, lactating, or nursing; Women of childbearing potential must have a negative urine pregnancy test prior to all infusions;
• Have unstable medical conditions (stable for less than 3 months) or with clinically significant laboratory values or an electrocardiogram (ECG) that would pose significant risk;
• Be at serious suicidal risk that cannot be managed in the outpatient setting;
• Have prior treatment for depression with or contraindications to ketamine, esketamine, or, midazolam;
• Treatment with medications that may alter pharmacokinetics of ketamine, including moderate-to-strong inhibitors or inducers of CYP3A4 and CYP2B6, is exclusionary. Regarding pharmacodynamic interactions, medications that may increase heart rate or blood pressure such as the ADHD stimulant medications will be permitted with last dose at least 24 hours prior to infusion. All concomitant medications will be evaluated by the study physician to determine if the type and dose of concomitant medication requires discontinuation and will be excluded if the concomitant medication could substantially increase the risk of study infusion. A complete list of medications that are Not Allowed is available in Appendix D of the protocol. The study team will not ask the participant to discontinue any treatment (except for not taking ADHD medications for 24 hours before study treatment) just for the sake of taking part in this study;
• Weigh >120 kilograms at baseline. If participants are enrolled but exceed 120 kilograms at any time during the treatment period, they will be removed from the treatment portion of the study.
Drug: Ketamine Hydrochloride, Drug: Midazolam Hydrochloride
Suicide, Attempted, Suicide and Depression, Suicide Threat
depression, adolescent, suicidal ideation, suicide attempt, teen, child, intensive outpatient, inpatient hospitalization, depression treatment, suicide treatment
UT Southwestern; Children’s Health
Study Assessing the Efficacy, Safety and PK of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (EPIK-P2)
This is a prospective Phase II multi-center study with an upfront 16-week, randomized, double-blind, placebo-controlled period, and extension periods, to assess the efficacy, safety and pharmacokinetics of alpelisib in pediatric and adult participants with PIK3CA-related overgrowth spectrum (PROS).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Caitlyn.Ambrose@childrens.com
Kathleen Ludwig
114894
ALL
2 Years and over
PHASE2
NCT04589650
STU-2021-0306
Inclusion Criteria:
• Signed informed consent and assent (when applicable) from the patient, parent, legal authorized representative or guardian prior to any study related screening procedures are performed
• Patients with diagnosis of PROS with symptomatic and /or progressive overgrowth and at least one measurable PROS-related lesion confirmed by blinded independent review committee (BIRC) assessment
• Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local laboratories
• A tissue sample (fresh or archival) is be sent to a Novartis-designated central laboratory. If archival tissue is not available, collection of a fresh tissue biopsy is required for participants in Groups 1, 2 and 5, if it is not clinically contraindicated. For participants in Groups 3 and 4, a fresh tissue biopsy is not mandatory. For China only: Tissue sample collection and biomarker assessments are not applicable. For Germany only: If archival tissue is available, it must be sent to a Novartis designated central laboratory. If no archival tissue is available, obtaining a fresh tissue biopsy is recommended, if it is not clinically contraindicated, but is not mandatory.
• Karnofsky (in patients \> 16 years old at study entry)/Lansky (≤16 yrs of age at study entry) performance status index ≥50
• Adequate bone marrow and organ function including Fasting plasma glucose (FPG) ≤ 140 mg/dL (7.7 mmol/L) and Glycosylated hemoglobin (HbA1c) ≤ 6.5% (both criteria have to be met) (as assessed by central laboratory for eligibility)
• Presence of at least one PROS-related measurable lesion defined as a lesion with longest diameter ≥2 cm, when the volume can be accurately and reproducibly measured by MRI (Magnetic resonance imaging), and associated with complaints, clinical symptoms or functional limitations affecting the patient's everyday life. Measurability must be confirmed by BIRC before randomization.
Exclusion Criteria:
• Participant with only isolated macrodactyly, skin nevus/nevi and macroencephaly (the only clinical feature or a combination of any of three of them), in absence of other PROS-related lesions at the time of informed consent
• Previous treatment with alpelisib and/or any other PI3K inhibitor(s) (except treatment attempt, defined as the attempt to treat PROS with any of PI3K inhibitors, with treatment duration less than 2 weeks and stopped at least 4 weeks prior to the first dose of study medication with alpelisib)
• Radiation exposure for PROS treatment purpose within the previous 12 months on those PROS areas which are expected to qualify for target lesions (except lesion(s) progressing after completion of radiotherapy) at time of informed consent.
• Debulking or other major surgery performed within 3 months at time of informed consent
• Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per CTCAE v.4.03) within 30 days before informed consent, and/or sclerotherapy/embolization for vascular complications performed within 6 weeks before informed consent. Note: Participants receiving anticoagulants for PROS-related coagulopathy, primary or secondary prophylaxis of thrombosis may be included in the study
• Participants in Groups 1, 2 ad 5 with documented pneumonitis or interstitial lung disease at time of informed consent and with impaired lung function (e.g., FEV1 or DLCO ≤ 70% of predicted) that is not related to PROS. Participants in Groups 3 and 4 with documented or suspicious pneumonitis or interstitial lung disease based on MRI images at time of informed consent
• History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis at time of informed consent
• Participants with an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at time of informed consent
• Known history of seizure, or epilepsy, regardless of relatedness to PROS spectrum at time of informed consent, when epilepsy is not controlled and/or the patient may not be switched to non-enzyme inducing antiepileptic drug(s) at time of informed consent.
• Participants with clinically significant worsening of PROS-related laboratory anomalies, physical signs and symptoms (such as, but not limited to increase of D-dimers, worsening of underlying pain, newly occurring swelling or redness) indicating an uncontrolled condition during the screening phase, particularly if systemic treatment with any other inhibitor of the PI3K/AKT/mTOR pathway was stopped prior to the start of study treatment. This includes but is not limited to hypercoagulability state in participants not receiving prophylactic treatment. Other inclusion/exclusion criteria may apply
DRUG: Alpelisib, DRUG: Placebo
Other, PIK3CA-Related Overgrowth Spectrum (PROS)
PIK3CA-related overgrowth spectrum (PROS), Alpelisib, BYL719, Adult, Pediatric, Phase II
Children’s Health
Comparing the New Anti-cancer Drug Eribulin With Chemotherapy Against the Usual Chemotherapy Alone in Metastatic Urothelial Cancer
This phase III trial compares the usual chemotherapy treatment to eribulin plus gemcitabine in treating patients with urothelial cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as eribulin, gemcitabine, docetaxel, paclitaxel, and sacituzumab govitecan 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. This trial aims to see whether adding eribulin to standard of care chemotherapy may work better in treating patients with metastatic urothelial cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
ALL
18 Years and over
PHASE3
NCT04579224
STU-2023-0199
Inclusion Criteria:
* Participant must have predominant histologically and cytologically proven urothelial carcinoma in a metastatic site
* Participant must have evidence of metastatic urothelial carcinoma based on CT or MRI within 28 days prior to registration
* Participant must have had progression of disease following prior therapy at the discretion of the treating investigator
* Participants must not require immediate central nervous system (CNS)-specific treatment, in the opinion of the treating investigator if they have active brain metastases (defined as new or progressive brain metastases) or leptomeningeal disease
* Participant must have had prior systemic therapy in metastatic setting that:
* Included enfortumab vedotin
* Included a PD1/PDL1 antibody
* NOTE: Under the discretion of the treating physician, participants who are not candidates for PD1/PDL1 antibody systemic therapy are allowed
* Any systemic therapy provided in adjuvant, neoadjuvant, or chemoradiation settings for urothelial carcinoma can be considered to be in metastatic setting, if the last day of treatment was within 12 months prior to the diagnosis of metastatic disease
* Participant must have completed any planned surgery or radiation therapy prior to registration
* Participant must not have unresolved toxicities from prior surgeries or radiation therapy \> grade 1 at the time of registration
* Participant must be ≥ 18 years of age
* Participant must have Zubrod performance status 0-2
* Participant must have history and physical examination within 28 days prior to registration
* Participant must have complete blood count (CBC), complete metabolic panel including liver function tests, and lactate dehydrogenase (LDH) obtained with 28 days prior to registration
* Participant must have adequate kidney function as evidenced by measured or calculated creatinine clearance \>= 20 mL/min within 28 days prior to registration
* Participant must have adequate hepatic function documented by either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (IULN) within 28 days prior to registration. If both AST and ALT are performed, both must be =\< 3 x IULN. For participants with liver metastases, AST or ALT must be =\< 5 x IULN
* Participant must be on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration if they are known to have human immunodeficiency virus (HIV)-infection
* Participants must have undetectable hepatitis B virus (HBV) viral load within 28 days prior to registration if participant has known chronic hepatitis B virus (HBV) infection
* Participants with a known history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load within 28 days prior to registration
* Participants may have a prior or concurrent malignancy provided the natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen per the opinion of the treating investigator
* Participants must not be planning to take strong or moderate CYP3A or CYP2C8 inhibitors or inducers if randomized to Arm 1 and standard of care (SOC) regimen chosen is paclitaxel or docetaxel. Participants receiving strong or moderate CYP3A- or CYP2C8 inducers must discontinue use at least 2 weeks prior to randomization
* Participant must not have a known history of corrected QT (QTc) prolongation
* Participants must not be pregnant or nursing due to the risk of harm to a fetus or nursing infant. Women and men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study and 6 months (females) or 3.5 months (males) after the last dose. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Docetaxel, DRUG: Eribulin Mesylate, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Paclitaxel, BIOLOGICAL: Sacituzumab Govitecan
Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Refractory Bladder Urothelial Carcinoma, Refractory Renal Pelvis Urothelial Carcinoma, Refractory Ureter Urothelial Carcinoma, Refractory Urethral Urothelial Carcinoma, Refractory Urothelial Carcinoma, Stage IV Renal Pelvis and Ureter Cancer AJCC v8, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8
UT Southwestern
A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
This phase III trial investigates the best dose of vinblastine in combination with selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib alone in treating children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment (recurrent) or does not respond to therapy (progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill cancer cells. Giving selumetinib in combination with vinblastine may work better than selumetinib alone in treating recurrent or progressive low-grade glioma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
10760
ALL
2 Years to 25 Years old
PHASE3
NCT04576117
STU-2021-0019
Inclusion Criteria:
* Feasibility phase: patients must be \>= 2 years and =\< 21 years of age at the time of enrollment
* Efficacy phase: patients must be \>= 2 years and =\< 25 years of age at the time of enrollment
* All patients \> 21 years of age at the time of enrollment must have had initial diagnosis of low-grade glioma by 21 years of age
* Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment
* Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1
* Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC) low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
* Patients must have progressive or recurrent LGG. Note: Biopsy may be at either initial diagnosis or recurrence
* Patients must have measurable disease, defined as having a two-dimensional measurable tumor volume of \>= 1 cm\^2
* Tumor size will be measured to include both solid and cystic components of the tumor (whether or not tumor is enhancing) + fluid attenuated inversion recovery (FLAIR) signal
* Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization \[WHO\] grade 1 and II) by the WHO Classification of Tumors of the Central Nervous System - 4th Edition Revised, with the exception of subependymal giant cell astrocytoma
* Patients with metastatic disease or multiple independent primary LGGs are eligible
* Patients must be progressive or recurrent after having been treated with at least one prior tumor-directed therapy before enrollment
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea);
* Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent;
* Radiation therapy (RT): \>= 2 weeks (wks) for local palliative RT (small port); \>= 6 months must have elapsed if prior craniospinal RT or if \>= 50% radiation of pelvis; \>= 6 wks must have elapsed if other substantial bone marrow (BM) radiation;
* 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;
* MEK inhibitor or vinblastine: Must not have received treatment with a MEK inhibitor or vinblastine within 6 months of study 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):
* 2 to \< 6 years: 0.8 mg/dL (male) 0.8 mg/dL (female)
* 6 to \< 10 years: 1 mg/dL (male) 1 mg/dL (female)
* 10 to \< 13 years: 1.2 mg/dL (male) 1.2 mg/dL (female)
* 13 to \< 16 years: 1.5 mg/dL (male) 1.4 mg/dL (female)
* \>= 16 years: 1.7 mg/dL (male) 1.4 mg/dL (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect \[unconjugated\] bilirubin levels as long as their direct \[conjugated\] bilirubin is \< 3.1 mg/dL)
* Serum glutamic pyruvic 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
* Albumin \>= 2 g/L (within 7 days prior to enrollment)
* Left ventricular ejection fraction (LVEF) \>= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (within 4 weeks prior to enrollment)
* Corrected QT interval (QTc interval) =\< 450 msec by electrocardiogram (EKG) (within 4 weeks prior to enrollment)
* Absolute neutrophil count \>= 1,000/uL (unsupported) (within 7 days prior to enrollment)
* Platelets \>= 100,000/uL (unsupported) (within 7 days prior to enrollment)
* Hemoglobin \>= 8 g/dL (may be supported) (within 7 days prior to enrollment)
* Patients with a known seizure disorder should be stable and should not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
* Stable neurological examination for \>= 1 week
* HYPERTENSION:
* Patients 2-17 years of age must have a blood pressure that is =\< 95th percentile for age, height, and gender at the time of enrollment (with or without the use of anti-hypertensive medications);
* Patients \>= 18 years of age must have a blood pressure =\< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
* Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
* All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment
* For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site\[s\] of primary disease) with and without contrast must be performed within 4 weeks prior to enrollment
* Note: If surgical resection or biopsy is performed at the time of progression or recurrence, a post-operative MRI is required
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have the ability to swallow whole capsules
Exclusion Criteria:
* Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following exceptions:
* Patients must not have had progressive disease while on therapy with vinblastine or a MEK inhibitor;
* Patients must not have discontinued vinblastine or selumetinib due to toxicity
* Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
* Patients with diffuse intrinsic pontine tumors as seen on MRI (\> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
* Patients may not be receiving any other investigational agents
* Patients must not have known hypersensitivity to selumetinib, vinblastine, or similar compounds
* CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
* Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
* Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
* PRE-EXISTING CONDITIONS (CARDIAC):
* Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented;
* Symptomatic heart failure
* New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
* Severe valvular heart disease
* History of atrial fibrillation
* PRE-EXISTING CONDITIONS (OPHTHALMOLOGIC CONDITIONS):
* Current or past history of central serous retinopathy
* Current or past history of retinal vein occlusion or retinal detachment
* Patients with uncontrolled glaucoma
* If checking pressure is clinically indicated, patients with intraocular pressure (IOP) \> 22 mmHg or upper limit of normal (ULN) adjusted by age are not eligible
* Any multivitamin containing vitamin E must be stopped prior to study enrollment even if it contains less than 100% of the daily recommended dosing for vitamin E
* Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy, placement of a vascular access device or cerebrospinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt
* Note: Patients must have healed from any prior surgery
* Patients who have an uncontrolled infection are not eligible
* Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible
* Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
* 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 PROCEDURE: Biospecimen Collection, PROCEDURE: Magnetic Resonance Imaging, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, DRUG: Selumetinib Sulfate, DRUG: Vinblastine Sulfate
Recurrent Low Grade Astrocytoma, Refractory Low Grade Astrocytoma, Refractory Low Grade Glioma, Recurrent WHO Grade 2 Glioma, Refractory WHO Grade 1 Glioma
Children’s Health
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
PHASE4
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 See if Memantine Protects the Brain During Radiation Therapy Treatment for Primary Central Nervous System Tumors
This phase III trial compares memantine to placebo 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
PHASE3
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
FUVID Study: Functional Characterization of Children With Chronic Venous Thromboembolic Disease
This is a multi-center prospective cohort study of patients with first-episode deep venous thrombosis and pulmonary embolism.
Call 214-648-5005
studyfinder@utsouthwestern.edu, kendra.malone@childrens.com, FUVID@utsouthwestern.edu
Ayesha Zia
149180
ALL
8 Years to 21 Years old
NCT04583878
STU-2020-0868
Inclusion Criteria:
* Ages 8 to ≤ 21 years
* Participant must be able to speak and understand English
* Be willing to participate and able to comply with the study protocol
* For participants with PE: Children with acute, radiologically confirmed pulmonary embolism (PE) with our without DVT
* For control group: Cohort 1: Children who are prescribed physical activity restrictions for 2 up to 12 weeks following any minor outpatient surgery or, minor injury (surgery or injury is referred to as "diagnosis" hereafter) Cohort 2: Children who are not prescribed physical activity restrictions and are otherwise considered to be healthy.
Exclusion Criteria:
* Congenital heart disease with abnormal pulmonary circulation or with in-situ pulmonary artery thrombosis
* Chronic kidney disease
* Chronic inflammatory or an autoimmune disorder (such as systemic lupus erythematosus, juvenile rheumatoid disorder, inflammatory bowel disease, and sickle cell disease)
* A metabolic or endocrinological disorder such as diabetes mellitus or thyroid disorder
* History of or active cancer
* Pregnant
* Musculoskeletal limitations to exercise expected to be present uptil 4 months post-diagnosis
* Weight ≥ 300 lbs
* Contraindications to magnetic resonance imaging
* Frequent severe exacerbations of asthma defined by two or more bursts of systemic glucocorticoids (more than three days each) in the previous year or at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous year. Patients should also be excluded if there are daily symptoms of asthma requiring daily use of short-acting bronchodilators such as albuterol or levalbuterol administration. The use of controller medications such as daily inhaled corticosteroids for mild persistent asthma is not exclusionary.
* Has any other medical condition, which in the opinion of the investigator may potentially compromise the safety or compliance of the patient or may preclude the patient's successful completion of the clinical study
Additional exclusion criteria for participants with PE:
* Prior history of DVT or PE (upper extremity, cerebral sinus venous thrombosis and abdominal thromboses encountered as a neonate are not exclusion criteria)
* Lack of anticoagulant treatment for the acute VTE due to contraindications DIAGNOSTIC_TEST: Blood draw (Visit 1), DIAGNOSTIC_TEST: Blood draw (Visits 2 and 3)
Pulmonary Embolism, Deep Venous Thrombosis, Cardiovascular, Lung/Thoracic
UT Southwestern; Children’s Health; Parkland Health & Hospital System
Youth Depression and Suicide Research Network (YDSRN)
The objective of this study is to build the Texas Youth Depression and Suicide Research Network to support the development of a Network Participant Registry and characterization of systems and interventions to examine statewide population health outcomes. All 12-13 sites represented in the Texas Child Mental Health Care Consortium (https://www.utsystem.edu/pophealth/tcmhcc/) have been invited to participate in the Texas Youth Depression and Suicide Research Network as "Nodes." 12 Nodes have been selected for this project. Each Node has obtained support of senior institutional leadership including the department chair. Leadership from each Node provided input and edits in the study design process by committee, with a focus on the inclusion of the "end user" in design decisions. Nodes will work closely with the Network Hub leadership to recruit, monitor, and retain participants. This will require active engagement and sustained relationships with clinics within the academic medical center as well as clinics in the community (i.e., psychiatry, psychology, counselling).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Lynnel.Goodman@UTSouthwestern.edu
Madhukar Trivedi
17410
ALL
8 Years to 20 Years old
NCT04572321
STU-2020-0665
Inclusion Criteria:
• Be 8 to 20 years of age;
• Have a positive screen for depression (e.g., based on PHQ-2 (score ≥3) and/or PHQ-A of 10 or greater, OR positive for suicidal ideation or behavior (e.g., based on CHRT-SR or PHQ-A item 9); OR be in treatment for depression;
• Be willing to provide consent/assent (parents/LAR/guardian or young adult participant, aged 18-20, must be willing to provide consent; youth, aged 8-17, must be willing to provide assent);
• Be able to speak English or Spanish sufficiently to understand the study procedures and provide written informed consent to participate in the study;
• Be willing to dedicate appropriate time to complete scheduled study assessments and measures (both parent/LAR/guardian and youth).
• Be able to provide a reliable means of contact.
Exclusion Criteria:
• Have an acute medical or psychological condition(s) that that would, in the judgment of the study medical clinician, make participation difficult or unsafe;
• Have an acute medical or psychological condition(s) that would result in an inability to accurately complete study requirements (e.g., neurological conditions or significant neurodevelopmental concerns);
• Have active psychotic symptoms resulting in altered mental status and inability to provide assent or requiring immediate attention and/or higher level of intervention;
• Have a parent/LAR/guardian who is deemed cognitively unable to provide consent (if youth participant, aged 8-17).
Depression, Suicidal Ideation, Suicide, Attempted, Depressive Disorder, Suicide, Depressive Episode, Depressive Symptoms, Depression and Suicide, Depression, Teen, Depression, Anxiety
depression, suicide, suicidal ideation, suicide attempt, teen, child, depressive episode, depression in teens
Children’s Health
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
PHASE2
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
A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease (GATEWAY)
The objectives of this clinical trial are to assess, for up to 5 years, the safety, tolerability and pharmacological activity of a single ascending doses of VTX-801, a gene therapy, administered intravenously (IV) to adult patients with Wilson's Disease prior to and following background WD therapy withdrawal.
Call 214-648-5005
studyfinder@utsouthwestern.edu, NAHID.ATTAR@UTSouthwestern.edu
William Lee
14217
All
18 Years to 65 Years old
Phase 1/Phase 2
NCT04537377
STU-2022-0533
Main
• Male or female aged 18 and 65 years inclusive
• Confirmed diagnosis of WD
• Treated for WD according to international recommendations with no current evidence for inadequate treatment
• Stable WD for ≥ 1 year, defined as: (i) No significant change in neurologic examination and in status of mood disorder and (ii) Stable laboratory parameters used to assess copper metabolism Main
• ALT level ≥ 2 ULN that is not readily explained by extrinsic factors
• Total bilirubin > 1.5 x ULN in the absence of proven Gilbert's syndrome; in case of Gilbert's syndrome, direct bilirubin > ULN
• INR > 1.2
• Any signs of liver cirrhosis decompensation, including gastrointestinal bleed within 6 months (24 weeks) prior to screening/enrollment visit
• Patient has moderate or severe renal impairment defined as eGFR CKD-EPI < 60 mL/min/1.73 m2, or patient has nephritis or nephrotic syndrome
• Any history or current evidence of HIV-1, HIV-2, HTLV 1, or HTLV-2 infection
• Any history or current evidence of hepatitis B infection
• Any history of hepatitis C infection, unless previous viral RNA assays in two samples, collected at least 6 months apart, are negative
• Positive QuantiFERON®-TB Gold tuberculosis test result
• Any concomitant disorder/condition - including hepatic disorders - or treatment possibly interfering with the conduct or evaluation of the study
• Any history of diabetes
• Pregnancy or breastfeeding
• Body Mass Index ≥ 35 kg/m2 Other protocol defined Inclusion/ Exclusion criteria may apply
Inclusion Criteria:
• Male or female aged 18 and 65 years inclusive
• Confirmed diagnosis of WD
• Treated for WD according to international recommendations with no current evidence for inadequate treatment
• Stable WD for ≥ 1 year, defined as: (i) No significant change in neurologic examination and in status of mood disorder and (ii) Stable laboratory parameters used to assess copper metabolism Main
Exclusion Criteria:
• ALT level ≥ 2 ULN that is not readily explained by extrinsic factors
• Total bilirubin > 1.5 x ULN in the absence of proven Gilbert's syndrome; in case of Gilbert's syndrome, direct bilirubin > ULN
• INR > 1.2
• Any signs of liver cirrhosis decompensation, including gastrointestinal bleed within 6 months (24 weeks) prior to screening/enrollment visit
• Patient has moderate or severe renal impairment defined as eGFR CKD-EPI < 60 mL/min/1.73 m2, or patient has nephritis or nephrotic syndrome
• Any history or current evidence of HIV-1, HIV-2, HTLV 1, or HTLV-2 infection
• Any history or current evidence of hepatitis B infection
• Any history of hepatitis C infection, unless previous viral RNA assays in two samples, collected at least 6 months apart, are negative
• Positive QuantiFERON®-TB Gold tuberculosis test result
• Any concomitant disorder/condition - including hepatic disorders - or treatment possibly interfering with the conduct or evaluation of the study
• Any history of diabetes
• Pregnancy or breastfeeding
• Body Mass Index ≥ 35 kg/m2 Other protocol defined Inclusion/ Exclusion criteria may apply
Genetic: VTX-801
Wilson's Disease
UT Southwestern
Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer
This phase II/III trial compares the effect of adding chemotherapy before and after surgery versus after surgery alone (usual treatment) in treating patients with stage II-III gallbladder cancer. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before surgery may make the tumor smaller; therefore, may reduce the extent of surgery. Additionally, it may make it easier for the surgeon to distinguish between normal and cancerous tissue. Giving chemotherapy after surgery may kill any remaining tumor cells. This study will determine whether giving chemotherapy before surgery increases the length of time before the cancer may return and whether it will increase a patient's life span compared to the usual approach.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Porembka
155238
ALL
18 Years and over
PHASE2
NCT04559139
STU-2021-0113
Inclusion Criteria:
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
* NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not eligible
* Patient must have undergone initial cholecystectomy within 12 weeks prior to randomization
* Patient must have the ability to understand and the willingness to sign a written informed consent document
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to randomization)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to randomization)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to randomization)
* Total bilirubin =\< institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome are eligible if direct bilirubin \< 1.5 x ULN of the direct bilirubin (obtained =\< 28 days prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 28 days prior to randomization)
* Serum creatinine =\< institutional ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 (Based on Cockcroft Gault estimation) (obtained =\< 28 days prior to randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
Exclusion Criteria:
* Patient must not have any evidence of metastatic disease or inoperable loco-regional disease based on high-quality, preoperative, cross-sectional imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) of the chest, abdomen, and pelvis (C/A/P) obtained within 6 weeks prior to randomization, defined as
* No radiographic evidence of distant disease (M1 disease)
* No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4 disease)
* No radiographic evidence of distant lymph node involvement (celiac, para-aortic, para-caval lymph nodes)
* No evidence of new-onset ascites
* Soft tissue thickening within or in direct communication with the gallbladder fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ, and other disease within the confines of what constitutes 'localized resectable' disease are allowable
* Women must not be pregnant or breast feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to randomization. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must not expect to conceive or father children by being strongly advised to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study DRUG: Cisplatin, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Lymphadenectomy, PROCEDURE: Partial Hepatectomy
Stage III Gallbladder Cancer AJCC v8, Stage IIIA Gallbladder Cancer AJCC v8, Stage IIIB Gallbladder Cancer AJCC v8, Liver, Stage II Gallbladder Cancer AJCC v8, Stage IIA Gallbladder Cancer AJCC v8, Stage IIB Gallbladder Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
187698
ALL
18 Years to 75 Years old
PHASE3
NCT04530565
STU-2021-0640
Inclusion Criteria:
* ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
* Patient must be \>= 18 and =\< 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
* Patient must be newly diagnosed with B acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (ALL)
* Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin step 1 therapy while awaiting central laboratory eligibility confirmation
* NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the ECOG-American College of Radiology Imaging Network (ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, with recommendation that adequate circulating blasts are present (\> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to step 1 without waiting for central confirmation
* Patient must not have a diagnosis of BCR/ABL T-ALL
* Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of therapy (hydroxyurea and/or steroids of any kind) with the aim to reduce disease burden prior to study registration to Step 1 are eligible
* Patient must not have unstable epilepsy that requires treatment
* Patients with lymphoid blast crisis chronic myeloid leukemia (CML) are not eligible
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
* Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
* Total bilirubin =\< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =\< 5 mg/dL) (obtained =\< 28 days prior to step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X the institutional upper limit of normal (ULN) (obtained =\< 28 days prior to step 1 registration)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation) (obtained =\< 28 days prior to step 1 registration)
* Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to step 2 randomization if the eligibility criteria outlined is met
* Patients who presented with no evidence of acute organ dysfunction but during step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment
* Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible
* Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during step 1. The investigator must re-specify dasatinib or ponatinib prior to step 2 randomization and from then on patients must receive the pre-selected TKI only
* ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
* Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted)
* NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional upper limit of normal (ULN)
* AST(SGOT)/ ALT(SGPT) =\< 2 X the institutional upper limit of normal (ULN)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive.
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization
* Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated
* Patients must have resolved any serious infectious complications related to therapy
* Any significant medical complications related to therapy must have resolved
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
* Institution has received centralized MRD results confirming positive status
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional ULN
* Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =\< 2 X institutional upper limit of normal (ULN)
* Patients who presented with acute organ dysfunction must have an estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined
* Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
* Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography, PROCEDURE: Electrocardiography, PROCEDURE: Lumbar Puncture, DRUG: Mesna, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Ponatinib Hydrochloride, DRUG: Prednisone, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1, Leukemia, Other
UT Southwestern
Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial (PROBE)
This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
ALL
18 Years and over
PHASE3
NCT04510597
STU-2021-0266
Inclusion Criteria:
* STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
* STEP 1 REGISTRATION: Participants must have primary tumor in place
* STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:
* Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
* CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast
Scans must be performed within the following timeframes:
* Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
* Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment
* STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
* STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
* STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
* CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
* CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2
• STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
* Stable disease
* Partial response
* The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1
* STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
* STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
* STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
* 2 infusions of nivolumab + 1 infusion of ipilimumab
* 2 infusions of pembrolizumab
* 2 infusions of avelumab
* STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
* STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
* STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
* STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
* STEP 2 REGISTRATION: Total bilirubin =\< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
* STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
* STEP 2 REGISTRATION: Serum creatinine =\< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance \>= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)
Exclusion Criteria:
* STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
* STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:
* Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
* Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
* STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:
* Treatment naive participants must not have received any pre-randomization treatment.
* Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:
* 4 infusions of nivolumab
* 4 infusions of ipilimumab
* 4 infusions of pembrolizumab
* 7 infusions of avelumab
* STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:
* Treatment naive participants must not have received any immunotherapy within a year of registration
* Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
* STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
* STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
* STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
* STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
* STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
* STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years PROCEDURE: Cytoreductive Nephrectomy, DRUG: Active Comparator
Metastatic Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern