Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
652 Study Matches
Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (TREAT-MS)
FDA-approved multiple sclerosis (MS) disease-modifying therapies (DMTs) target the relapsing
phase of MS but have minimal impact once the progressive phase has begun. It is unclear if,
in the relapsing phase, there is an advantage of early aggressive therapy with respect to
preventing long-term disability. The infectious risks and other complications associated with
higher-efficacy treatments highlight the need to quantify their effectiveness in preventing
disability.
The TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial is a pragmatic,
randomized controlled trial that has two primary aims: 1) to evaluate, jointly and
independently among patients deemed at higher risk vs. lower risk for disability
accumulation, whether an "early aggressive" therapy approach, versus starting with a
traditional, first-line therapy, influences the intermediate-term risk of disability, and 2)
to evaluate if, among patients deemed at lower risk for disability who start on first-line MS
therapies but experience breakthrough disease, those who switch to a higher-efficacy versus a
new first-line therapy have different intermediate-term risk of disability.
• Aged 18-60 years
• Meets 2017 McDonald criteria for relapsing-remitting MS [patients with clinically
isolated syndrome (CIS) are not eligible]
• Must be EITHER John Cunningham (JC) virus antibody negative or low positive (index
antibody titer <0.9), OR negative for: Hepatitis B and C, tuberculosis
• HIV negative
• No chemotherapy in past year; if patient has prior history of chemotherapy or
malignancy, documentation in chart explaining why potential risks of higher-efficacy
therapy are justified
Exclusion Criteria:
• Prior treatment with rituximab, ocrelizumab, ofatumumab, alemtuzumab, mitoxantrone or
cladribine
• Prior treatment with any other MS DMT for more than 6 months
• Prior treatment with experimental aggressive therapies (e.g., T-cell vaccine, total
lymphoid radiation, stem cells)
• Treatment with teriflunomide within past 2 years (even for ≤ 6 months), unless rapid
wash out done (i.e., with cholestyramine or activated charcoal)
• Treatment in the past 6 months with any MS DMT
• Prior treatment with any other investigational immune-modulating /suppressing drug for
MS not listed above
• Pregnant or breast-feeding
• Women of child-bearing age who are planning or strongly considering conception during
the study time frame
Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer (TAILOR RT)
The purpose of this study is to compare the effects on low risk breast cancer receiving usual
care that includes regional radiation therapy, with receiving no regional radiation therapy.
Researchers want to see if not giving this type of radiation treatment works as well at
preventing breast cancer from coming back.
* Patients must be women with newly diagnosed histologically proven invasive carcinoma of the breast with no evidence of metastases, staged as per site standard of care.
* Patients must have been treated by BCS or mastectomy with clear margins of excision. Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed. Multifocal disease (i.e. the presence of two or more foci or breast cancer within the same breast quadrant) and multicentric disease (i.e. the presence of two or more foci of breast cancer in different quadrants of the same breast) are allowed.
* Patients with T3N0 disease are eligible.
* Patients with disease limited to nodal micrometastases are eligible
* Patients with nodal macrometastases (\>2mm) treated by axillary dissection must have 1-3 positive axillary nodes (macrometastases, \> 2 mm).
* Patients treated by mastectomy and SLNB alone must have only 1-2 positive axillary nodes (macrometastases, \> 2 mm).
* Patients must be ER ≥ 1% and HER2 negative on local testing
* Patients must have an Oncotype DX recurrence score ≤25 obtained from testing of breast tumour tissue from a core biopsy or from the surgical specimen.
* Patient must consent to provision of, and investigator(s) must agree to submit to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays described in the protocol may be conducted
* Patient must consent to provision of samples of blood in order that the specific correlative marker assays described in the protocol may be conducted.
* Patients must have had endocrine therapy initiated or planned for ≥ 5 years. Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine therapy can be given concurrently or following RT.
* Patients may or may not have had adjuvant chemotherapy.
* RT must commence within 16 weeks of definitive surgery if the patient is not treated with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of randomization). Definitive surgery is defined as the last breast cancer-related surgery.
* Patient's ECOG performance status must be 0, 1 or 2.
* Patient's age must be ≥ 35 years.
* For the first 736 eligible English or French-speaking subjects who have agreed to optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life, health utilities and lost productivity questionnaires in either English or French (note: enrollment completed 2022Aug02)
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
* Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* In accordance with CCTG policy, protocol treatment is to begin within 6 weeks of patient randomization.
* Women of childbearing potential must have agreed to use an effective contraceptive method. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months.
Exclusion Criteria:
* Patients with nodal disease limited to isolated tumour cells (pN0i+ \< 0.2 mm).
* Patients with pT3N1 and pT4 disease (Note: patients with T3N0 are eligible).
* Any prior history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
* Synchronous or previous contralateral invasive breast cancer. (Patients with contralateral DCIS are eligible unless previously treated with radiation.)
* History of non-breast malignancies except adequately treated non-melanoma skin cancers, in situ cancers treated by local excision or other cancers curatively treated with no evidence of disease for ≥ 5 years.
* Patients who are pregnant.
* Patients that have had prior ipsilateral chestwall/thoracic radiation.
* Patients treated with chemo or endocrine therapy administered in the neoadjuvant setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to surgery is permitted.
* Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.) which would preclude RT.
* Patients with any serious active or co-morbid medical conditions, laboratory abnormality, psychiatric illness, active or uncontrolled infections, or serious illnesses or medical conditions that would prevent the patient from participating or to be managed according to the protocol (according to investigator's decision).
RADIATION: Radiation, OTHER: No Radiation
Breast Cancer
UT Southwestern; Parkland Health & Hospital System
Pioglitazone to Reduce Sympathetic Overactivity in CKD Patients
Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular disease and
death. An overactive sympathetic nervous system in CKD patients is one of the major
mechanisms increasing the cardiovascular risks in this patient population. Recently, some
studies have shown that a drug typically used to improve glucose control (pioglitazone) may
also reduce sympathetic nerve activity and improve blood vessel function.
The goal of this study is to determine whether a short-term treatment with pioglitazone can
reduce sympathetic nerve impulses throughout the body in CKD patients.
• CKD patients classified as Stage 3 and 4 of National Kidney Foundation Classification
with estimated glomerular filtration rate (GFR) between 15 and 59 mL/min/1.73 m2
according to the Modification of Diet in Renal Disease (MDRD) formula based on serum
creatinine, age, gender, and race.
• Men and women 35 to 70 years of age
Exclusion Criteria:
• Allergy to Glitazones
• Myocardial infarction
• Heart failure
• Angina
• History of kidney stones
• Liver disease (abnormal liver enzymes)
• Anemia (hemoglobin <8 g/dl)
• Cancer with current treatment
• Previous organ transplantation
• Immunosuppressant therapy
• Human immunodeficiency virus infection
• Pregnancy or lactating
• Current tobacco use
• Dilantin and oral contraceptive usage due to potential drug interaction with
glitazones
• Self-identified history of hypoglycemia
Drug: Pioglitazone, Other: Placebo
Chronic Kidney Diseases, Kidney
blood pressure, pioglitazone, hypertension
UT Southwestern; Parkland Health & Hospital System
The RAD study is a longitudinal study to prospectively characterize the biological mechanisms
of resilience in adolescents and young adults at risk for developing depression. The study
will capture biomarkers from the domains of socio-demographic and clinical data, cognitive
and psychological assessments, fluid-based biomarkers, neuroimaging and EEG. Such biomarkers
will compose a human biosignature of resilience and identify risk factors for depression,
contributing to effective treatment selection or may represent moderators of response or
non-response to treatments in subjects with depression. A cohort of 1,500 participants, age
10-24 will be recruited over a 5 year period. Participants will be followed for 10 years
following an initial baseline visit. Study visits are conducted 4 times per year.
• Adolescents and young adults aged 10-24, male and female of all races and ethnicity.
• Participants must be English-speaking (because several study assessments are only
available in the English language), however the parent(s) or legal guardian may either
speak English or Spanish as the consenting process can be conducted bilingually.
• Adults age 18 and older must be able to provide written informed consent; for youth
younger than age 18, a parent or legal guardian must provide written informed consent,
and the child or teen must provide written informed assent.
• Ability to complete clinical evaluations and neuropsychological testing.
Exclusion Criteria:
• Individuals who are unable to provide informed consent.
• Participants who are non-English speaking.
• Individuals with any of the following psychotic features: MDD with psychotic features,
schizophrenia, schizoaffective disorder, or other Axis I psychotic disorder.
• Individuals with a depression diagnosis or a history of depression diagnosis at the
initial visit (participants who develop depression during the longitudinal follow-up
will continue in the study).
• A PHQ-9 score of 10 or greater.
• Individuals who are unable to provide a permanent home address and contact
information.
• Individuals with any condition for which, in the opinion of the investigator, study
participation would not be in their best interest (e.g., compromise their well-being)
or that could prevent, limit, or confound the protocol-specified assessments.
• Postnatal age 48 hours -21 days
• Infant 22 0/7 to 28 6/7 weeks gestation at birth
• sPDA, as defined as:
• Mild, Moderate, or Severe Clinical Criteria with Small or Moderate size PDA on
echocardiogram
• Mild or Moderate Clinical Criteria with Large PDA on echocardiogram
Exclusion Criteria:
• Cardiopulmonary compromise
• Known congenital heart disease (besides atrial septal defect or ventricular septal
defect)
• Known pulmonary malformation (e.g. congenital lobar emphysema, congenital pulmonary
adenomatous malformation)
• Any condition which, in the opinion of the investigator, would preclude enrollment
Other: Active Treatment, Other: Expectant Management
Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 In The Treatment Of Adult
Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant
Prostate Cancer (CRPC) And Follicular Lymphoma (FL).
Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts:
Part 1A (closed to enrollment):
Part 1B (closed to enrollment):
Part 1C:
* Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) Japan cohort
* Castration resistant prostate cancer that is resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) China cohort
* Castration resistant prostate cancer that is intolerant/resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients who refused SOC may be eligible. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3)
Part 2A:
• Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment, may have received up to 1 line of chemotherapy and have evidence of prostate cancer progression (per PCWG3)
Part 2B/2C:
* Metastatic Castration resistant prostate cancer. Patients should have received abiraterone treatment, may have received up to 1 prior line of chemotherapy, have not received prior enzalutamide, apalutamide or darolutamide and have evidence of prostate cancer progression (per PCWG3)
* Patients must have radiographic evidence of disease
Other inclusion criteria:
-Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
Key
Exclusion Criteria:
• Prior Chemotherapy: Part 1C , Japan cohort and China cohort (CRPC): no more than 2 previous regimens of chemotherapy Part 2A: mCRPC: no more than 1 previous regimen of systemic chemotherapy Part 2B (mCRPC): no more than 1 previous regimen of chemotherapy
* Prior irradiation to \>25% of the bone marrow.
* QTcF interval \>480 msec at screening.
* Hypertension that cannot be controlled by medications (\>150/90 mmHg despite optimal medical therapy).
* Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC)
* Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.
* Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inducers or inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational product.
The purpose of this study is to (1) investigate the effect of known dystonia-causing
mutations on brain structure and function, to (2) identify structural brain changes that
differ between clinical phenotypes of dystonia, and to (3) collect DNA, detailed family
history, and clinical phenotypes from patients with idiopathic dystonia with the goal of
identifying new dystonia-related genes. Investigators will be recruiting both healthy control
subjects and subjects with any form of dystonia. For this study there will be a maximum of
two study visit involving a clinical assessment, collection of medical and family history,
task training session, an MRI using the learned tasks, and finally a blood draw for genetic
analysis. In total, these visits will take 3-5 hours. If the dystonia subjects receive
botulinum toxin injections for treatment, the participants and their matched controls will be
asked to come for a second visit.
General Exclusion (both Dystonia and Control groups):
* Metal in any part of the body (including metal injury to the eye) OR carrying a medical device incompatible with MRI (e.g., metal implants such as surgical clips or pacemakers) OR positive screening per UTSW MRI screening form
* Claustrophobia
* Non-fluent English
* Weight incompatible with MRI safety
* History of head trauma with neurological sequelae, including multiple concussions and/or history of stroke
* Pregnancy
* Serious medical illness or history of serious medical illness, including cancer that was treated with radiation or chemotherapy, heart attack, or a known history of HIV-1 + status
* Subjects with Hepatitis C (by Hepatitis C+ titer)
* Subjects with insulin dependent diabetes mellitus (IDDM)
* Severe respiratory compromise
* In the opinion of the investigator, not able to safely participate in this study
Inclusion Criteria:
* Dystonia group
Previous diagnosis of dystonia which include but is not limited to:
* cervical dystonia (50 subjects)
* blepharospasm (25 subjects)
* limb dystonia (50 subjects)
* spasmodic dysphonia (25 subjects)
* segmental dystonia
* multi-focal dystonia
* Any childhood-onset dystonia (25 subjects) Age \> 11 years
* Control group:
No prior dystonia diagnosis (175 subjects) Age \> 11 years
Exclusion Criteria:
* Dystonia group Prior history of or concurrent neurological or psychiatric diagnosis - depression and/or anxiety accepted Current use of non-dystonia neuroactive medications - SSRI/medication for depression and/or anxiety accepted Current use of cervical brace designed for dystonia treatment Prior structural brain injury
Control group:
History of or current neurological or psychiatric diagnosis - depression and/or anxiety accepted, but must not be in active phase Current use of any neuroactive medication, SSRI/medication for depression and/or anxiety accepted
Adoptive Cell Therapy Long-term Follow-up (LTFU) Study
This is a non-therapeutic, multi-center, long-term follow-up (LTFU) study of subjects who
have, during the interventional study, received GSK3377794 generated by a process that
utilizes lentiviral vectors. Subjects enrolled in the interventional studies who complete the
interventional study or who withdraw from the interventional study will enter this LTFU study
and will be followed for up to 15 years from the infusion of genetically modified T
lymphocytes. Subjects can receive other therapies for their cancer while they are being
followed for long term safety in this study.
* Participants who have received at least one dose of ADP adoptive cell therapy agent.
* Participants who have completed ADP sponsored or supported interventional study or have withdrawn from it.
* Participants who have completed treatment as part of managed access to a GSK adoptive cell therapy.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* The investigator is responsible for review of medical history.
* Capable of giving signed informed consent.
Exclusion Criteria:
• None
BIOLOGICAL: ADP adoptive cell therapy
Neoplasms
Long Term Follow Up, Adoptive Cell Therapy, Replication Competent Lentivirus
CHaractErizing CFTR Modulated Changes in Sweat Chloride and Their Association With Clinical Outcomes (CHEC-SC)
This is a multicenter, cross-sectional, cohort study which will collect contemporary sweat
chloride (SC) values from approximately 5000 Cystic Fibrosis (CF) patients prescribed and
currently receiving commercially approved Cystic Fibrosis transmembrane conductance regulator
(CFTR) modulator therapies.
• Written informed consent (and assent when applicable) obtained from subject or
subject's legal representative
• Enrolled in the CFFPR
• Male or female ≥ 4 months of age on day of study visit
• Diagnosis of CF.
• Current treatment with a prescribed commercially approved CFTR modulator for at least
90 days prior to enrollment
• Able to perform the testing and procedures required for this study, as judged by the
investigator
Additional Inclusion Criteria for CHEC-PKPD Sub-Study:
• Male or female ≥ 6 years of age on day of study visit.
• Current treatment with elexacaftor/tezacaftor/ivacaftor for at least 90 days prior to
enrollment.
• Last dose of elexacaftor/tezacaftor/ivacaftor taken at least 24hours and last dose of
ivacaftor taken at least 12 hours prior to trough blood draw on day of visit.
Exclusion Criteria:
• Presence of a condition or abnormality that, in the opinion of the Investigator, would
compromise the safety of the patient or the quality of the data
• Currently enrolled in an investigational trial (including open-label follow-on studies
and Early Access Programs (EAP) of an agent expected to have an impact on sweat
chloride (refer to current list provided on study website)
Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
This is a Phase 1/2, open-label, multicenter study to determine the efficacy and safety of
JCAR017 in adult subjects with relapsed or refractory CLL or SLL. The study will include a
Phase 1 part to determine the recommended dose of JCAR017 monotherapy in subjects with
relapsed or refractory CLL or SLL, followed by a Phase 2 part to further assess the efficacy
and safety of JCAR017 monotherapy treatment at the recommended dose. A separate Phase 1
cohort will assess the combination of JCAR017 and concurrent ibrutinib. Another separate
Phase 1 cohort will assess the combination of JCAR017 and concurrent venetoclax. In all
subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.
* Diagnosis of:
• CLL with an indication for treatment based on the Investigator's opinion and measurable disease, or
• SLL (lymphadenopathy and/or splenomegaly and \< 5×10\^9 CD19+ CD5+ clonal B lymphocytes/L \[\< 5000/µL\] in the peripheral blood at diagnosis with measurable disease that is biopsy-proven SLL)
* Subjects (other than those in the ibrutinib + JCAR017 combination therapy and DEME cohort) must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy.
* Subjects in the JCAR017 monotherapy cohorts must have received previous treatment as follows:
• Monotherapy cohorts EXCEPT DEME cohort: Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy.
• Monotherapy cohorts EXCEPT DEME cohort: Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy.
• DEME cohort ONLY: Subjects with relapsed or refractory CLL or SLL, irrespective of cytogenetic risk features, must have received at least 2 lines of prior therapy including a BTKi and a BCL2i.
* Subjects in the ibrutinib + JCAR017 combination therapy cohort must either:
• be receiving ibrutinib and progressing at the time of study enrollment
• be receiving ibrutinib for at least 6 months with a response less than complete response/remission (CR) and have high-risk features as defined in inclusion criterion 5a
• have BTK or PLCgamma2 mutations per local laboratory assessment, with or without progression on ibrutinib
• have previously received ibrutinib and have no contraindications to restarting ibrutinib
* Eastern Cooperative Oncology Group performance status of ≤ 1
* Assessed by the Investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy
* Adequate organ function, defined as:
• Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance \> 30 mL/min
• Alanine aminotransferase ≤ 5 × ULN and total bilirubin \< 2.0 mg/dL (or \< 3.0 mg/dL for subjects with Gilbert's syndrome or leukemic infiltration of the liver)
• Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air
• Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% as assessed by echocardiogram or multiple uptake gated acquisition scan performed within 30 days prior to determination of eligibility
* Subject either currently has central vascular access or is a candidate to receive central vascular access or peripheral vascular access for leukapheresis procedure.
* If prior CD19-targeted therapy has been administered, subject must have CD19-positive disease confirmed by immunohistochemistry or flow cytometry since completing the prior CD19-targeted therapy.
* Subjects in ibrutinib + JCAR017 combination cohort must have progressed on a BTKi and have received prior therapy with venetoclax
* Subjects in venetoclax + JCAR017 combination cohort must:
• have failed at least 1 prior line of therapy, including failed BTKi therapy or have been deemed ineligible to receive BTKi
• be venetoclax naive (required for dose expansion) or
• if prior venetoclax (only for dose escalation)
• have no contraindictions to re-initiation of venetoclax based on prior intolerance and have had at least 6 months elapsed since the last dose of venetoclax, if either, best response was stable disease, or subject experienced disease progression on venetoclax, or within 6 months of venetoclax discontinuation
* subjects in the venetoclax + JCAR017 combination must have hemoglobin \>=9 g/dL, absolute neutrophil count \>=500mm3 and platelets\>= 75,000/mm3, unless cytopenias are judged by investigator to be due to CLL infiltration of the bone marrow
* must have diagnosis of CLL or SLL with an indication for treatment based on the investigator's opinion and measurable disease (any of the following measurable lymph nodes ≥1.5 cm in the greatest transverse diameter and/or hepatomegaly or splenomegaly) and demonstration of CLL cells in the peripheral blood by flow cytometry
Exclusion Criteria:
* Subjects with known active central nervous system (CNS) involvement by malignancy. Those with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.
* History of another primary malignancy that has not been in remission for at least 2 years. (The following are exempt from the 2-year limit: nonmelanoma skin cancer, completely resected stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.)
* Subjects with Richter's transformation
* Prior treatment with any gene therapy product
* Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV) infection
* Systemic fungal, bacterial, viral, or other infection that is not controlled
* Presence of acute or extensive chronic graft versus host disease (GVHD)
* History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
* History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, aphasia, stroke with current neurologic sequelae, severe brain injuries, dementia, Parkinson's disease, cerebellar disease,cerebral edema, or psychosis
* Pregnant or nursing (lactating) women
* Use of any of the following medications or treatments within the noted time prior to leukapheresis:
• Alemtuzumab within 6 months prior to leukapheresis
• Allogeneic hematopoietic stem cell transplant within 100 days prior to leukapheresis
• Cladribine within 3 months prior to leukapheresis
• Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis
• Radiation including large bone marrow fields such as sternum or pelvis within 6 weeks prior to leukapheresis
• Fludarabine within 4 weeks prior to leukapheresis
• GVHD therapies such as calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate mofetil, rapamycin, or immunosuppressive antibodies (such as anti-tumor necrosis factor-α \[TNFα\], anti-interleukin-6 \[IL-6\], or anti-interleukin-6 receptor \[IL 6R\]) within 4 weeks prior to leukapheresis
• Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis
• Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis
• Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis
• Venetoclax within 4 days prior to leukapheresis
• Idelalisib or duvelisib within 2 days prior to leukapheresis
• Lenalidomide or covalent and non-covalent BTKi within 1 day prior to leukapheresis
• Experimental agents, including off-label use of approved drugs (with the exception of acalabrutinib which may be continued up to the day before leukapheresis), within 4 weeks prior to leukapheresis unless progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis
* Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or subject unwillingness or inability to follow the procedures required in the protocol
* Progressive vascular tumor invasion, thrombosis, or embolism
* Deep vein thrombosis or embolism not managed on a stable regimen of anticoagulation
* Use of any of the following medications or treatments within the noted time prior to leukapheresis lenalidomide or acalabrutinib within 1 day prior to leukapheresis experimental agents, including off-label use of approved drugs, within 4 weeks prior to leukapheresis.
* Venous thrombosis or embolism requiring treatment but not managed on a stable regimen of anticoagulation
* For subjects in the venetoclax + JCAR017 combination cohorts only, concomitant treatment with CYP3A moderate/strong inducers or moderate/strong inhibitors which cannot be discontinued
A Study of CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma
This is a multi-center, open-label trial to evaluate the safety, pharmacokinetics (PK), and
anti-cancer activity of oral administration of emavusertib (CA-4948) in adult patients with
relapsed or refractory (R/R) hematologic malignancies. Part A will evaluate the safety and
tolerability of escalating doses of emavusertib as monotherapy (Part A1), and in combination
with ibrutinib. In Protocol Version (v) 1.0 through v6.0, patients with Waldenström
macroglobulinemia/ lymphoplasmacytic lymphoma (WM/LPL) and chronic lymphocytic leukemia
(CLL)/small lymphocytic lymphoma (SLL) were also enrolled at ibrutinib doses of 420 mg (Part
A2). Enrollment into Parts A1 and A2 has been closed. Part B will comprise 2 cohorts to
assess safety and efficacy of emavusertib in combination with ibrutinib in patients with
primary central nervous system lymphoma (PCNSL).
• Males and females greater than or equal to 18 years of age
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable). Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
• Patients with parenchymal lesions must have unequivocal evidence (e.g., presence of at least 1 bi-dimensionally measurable target lesion on brain magnetic resonance imaging (MRI) or head CT or a new lesion with CSF involvement) of disease progression on imaging within 28 days prior to Cycle 1 Day 1.
• For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells or monotypic cells on flowcytometry, and/or imaging findings consistent with CSF disease within 28 days prior to Cycle 1 Day 1 (at the discretion of the Investigator).
Exclusion Criteria for Part B - PCNSL Expansion Cohorts of Combination Therapy
• Patients with only intraocular PCNSL without brain lesion or CSF involvement or T-cell lymphoma or systemic presence of lymphoma, or non-CNS lymphoma metastatic to the CNS
• Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior history of systemic lymphoma, unless the patient has been free of the disease for ≥ 3 years.
• Active malignancy other than PCNSL requiring systemic therapy
• History of Grade ≥ 3 rhabdomyolysis without complete recovery
• Patient has received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.
• Prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to C1D1; or clinically significant graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior to Screening Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical Monitor approval
• Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1 (with the exception of ibrutinib, which may be continued as part of this study without interruption)
• Prior history of hypersensitivity or anaphylaxis to emavusertib or ibrutinib or any excipients.
DRUG: Emavusertib, DRUG: ibrutinib
Relapsed Hematologic Malignancy, Refractory Hematologic Malignancy, Relapsed Primary Central Nervous System Lymphoma, Refractory Primary Central Nervous System Lymphoma
MYD88, IRAK4, NHL, MZL, PCNSL, Lymphoma, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, Non-Hodgkin, Relapsed/refractory Central Nervous System (CNS) Lymphoma, Systemic Lymphoma with Concurrent CNS Lymphoma, Systemic Lymphoma with a History of Treated CNS Lymphoma, Ibrutinib, Bruton's tyrosine kinase (BTKi)
• Must have given written informed consent (signed and dated)
• Participated in a PBC study with seladelpar
• Females of reproductive potential must use at least one barrier contraceptive and a
second effective birth control method during the study and for at least 90 days after
the last dose. Male subjects who are sexually active with female partners of
reproductive potential must use barrier contraception and their female partners must
use a second effective birth control method during the study and for at least 90 days
after the last dose
Exclusion Criteria:
Exclusion criteria are only applicable for subjects with a seladelpar interruption greater
than 4 weeks prior to Day 1 of this study and for subjects who participated in CB8025-21838
irrespective of seladelpar interruption.
• Treatment-related adverse event (AE) leading to seladelpar discontinuation in a
previous PBC study with seladelpar (MBX-8025)
• A medical condition, other than PBC, that in the investigator's opinion would preclude
full participation in the study or confound its results (e.g., cancer)
• AST or ALT above 3 × the upper limit of normal (ULN)
• Total bilirubin above 2 × ULN
• MELD score ≥ 12. For subjects on anticoagulation medication, evaluation of the
baseline INR, in concert with any current dose adjustments in anti-coagulant
medications, will be taken into account when calculating this score. This will be done
in consultation with the medical monitor.
• Evidence of advanced PBC as defined by the Rotterdam criteria: albumin below 1× the
lower limit of normal (LLN) AND total bilirubin above 1 × ULN)
• eGFR ≤45 mL/min/1.73 m2 (calculated by MDRD formula)
• Auto-immune hepatitis
• Primary sclerosing cholangitis
• Known history of alpha-1-antitrypsin deficiency
• Known history of chronic viral hepatitis
• For females, pregnancy or breast-feeding
• Use of colchicine, methotrexate, azathioprine, or long-term use of systemic steroids
(e.g. prednisone, prednisolone, budesonide) (>2 weeks) within 2 months prior to
Screening
• Current use of fibrates or use of fibrates within 3 months prior to Screening
• Current use of obeticholic acid or use of obeticholic acid within 3 months prior to
Screening
• Use of an experimental or unapproved treatment for PBC within 3 months prior to
Screening
• History of malignancy diagnosed or treated, actively or within 2 years, or active
evaluation for malignancy; localized treatment of squamous or non-invasive basal cell
skin cancers and cervical carcinoma in-situ is allowed if appropriately treated prior
to Screening
• Treatment with any other investigational therapy or medical device within 30 days or
within 5 half-lives, whatever is longer, prior to Screening
• Any other condition(s) that would compromise the safety of the subject or compromise
the quality of the clinical study, as judged by the Investigator
• Immunosuppressant therapies (e.g., cyclosporine, tacrolimus, anti-TNF or other
immunosuppressive biologics)
• Other medications that effect liver or GI functions such as absorption of medications
or the roux-en-y gastric bypass procedure may be prohibited and should be discussed
with the medical monitor on a case-by-case basis
• Positive for:
• Hepatitis B, defined as the presence of hepatitis B surface antigen
• Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid (RNA)
• Human immunodeficiency virus (HIV) antibody
• Active COVID-19 infection during screening
• Histologically or Cytopathology confirmed pancreatic adenocarcinoma with initial diagnosis within 6 weeks of consent for patients who enroll at cycle 1, and from the start of cycle 1 of gemcitabine + nab-paclitaxel chemotherapy for patients who enroll at cycle 2
• Locally advanced, unresectable disease at screening and prior to randomization, as defined by NCCN criteria determined by an on-site, experienced, multidisciplinary team (as confirmed by CT or MRI within 30 days of the start of cycle 1)
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
• Age ≥ 18 years
• Adequate laboratory values prior to receiving the first dose of nab-paclitaxel and gemcitabine: (criterion must be met prior to cycle 2.) For a subject with elevated bilirubin, AST or ALT, who has had a biliary stent placed, if the subject's lab values have returned to within the required range for eligibility noted below in sub-criteria e and f \[(AST) ALT ≤ 3.0 X the upper normal limit, and total bilirubin ≤ 1.5 X the upper normal limit\] after placement of stent and prior to cycle 2, he/she is eligible for the study. Additional detail regarding eligibility for subjects who have had biliary stents recently placed is outlined in sub-criteria f and h below.
• Absolute neutrophil count (ANC) ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine \>1.5 mg/dL
• \*Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 X the upper normal limit of institution's normal range
• \*Total bilirubin ≤ 1.5 X the upper normal limit of institution's normal range -OR- If biliary stent is placed or planned to be placed within 6 weeks of Cycle 1 Day 1 (C1D1), total bilirubin ≤ 2.0 X the upper normal limit of institution's normal range (see section 9.1.4 for dose modification due to elevated bilirubin)
• Prothrombin time (PT) and partial thromboplastin time (PTT) must be ≤ 1.5 X upper normal limit of institution's normal range. Subjects who are currently taking anti-coagulant therapy are eligible if not meeting this criterion
• International normalized ration (INR) ≤ 1.5 X upper normal limit of institution's normal range. Subjects who are currently taking anti-coagulant therapy are eligible if not meeting this criterion \*For elevated AST, ALT, and total bilirubin at screening, subject must have a normalized result prior to initiation of Cycle 2 if abnormal labs are considered related to bile duct obstruction and a biliary stent has been placed
• Life expectancy \> 12 weeks
• Negative pregnancy test for women of childbearing potential (either serum or urine) within one day prior to administration of the first dose of chemotherapy. Women of childbearing potential should use highly effective methods of contraception during treatment and for up to 6 months following treatment cessation
• Provide written informed consent
• Subjects willing to participate in the study for at least 8 months if randomized to IA gemcitabine OR IV gemcitabine + nab-paclitaxel
Exclusion Criteria:
• Any prior treatment for pancreatic cancer OR more than one cycle of gemcitabine and nab-paclitaxel treatment. For subjects who have started on their first cycle of gemcitabine and nab-paclitaxel treatment prior to consent, Inclusion Criterion #1 only applies to the first gemcitabine and nab-paclitaxel dose and must be within 6 weeks of confirmed diagnosis
• Any evidence of metastatic disease or another active malignancy within the past one year except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
• Subjects unable or unwilling to have their first randomized treatment within 3 weeks of the post induction imaging and within 5 weeks of their last induction treatment
• Subjects without baseline tumor imaging
• As determined by the Sponsor:
Arterial anatomy unsuitable for IA delivery of gemcitabine to the intended tumor site, determined by CT or MRI, as determined and approved by the Sponsor Imaging Advisor, which includes the following:
• Stenosis or occlusion in the intended artery for treatment
• Inability to exclude major side branches in the area of the intended RenovoCath® catheter occlusion
• No suitable artery with a diameter greater than 3 mm in proximity of at least one side of the tumor
• Superior mesenteric vein (SMV) occlusion or stenosis that cannot be resolved with medication or intervention prior to randomization, if the superior mesenteric artery (SMA) is the only viable treatment artery Note: Arterial Anatomy will be reviewed by the Sponsor, RenovoRx Imaging Advisor, and RenovoRx Medical Monitor for approval
• Contraindications for SBRT planning which includes the following:
• Gastrointestinal mucosal infiltration evident at the time of diagnostic endoscopy
• Prior abdominal radiotherapy judged to have clinically significant degree of overlap with planned SBRT dose distribution Note: Primary tumors with a diameter greater than 7 cm must be assessed on a case-by-case basis with the RenovoRx Imaging Advisor prior to excluding the subject from the trial.
• Subjects with known HIV infection or active viral hepatitis
• Severe infections requiring hospitalization within 4 weeks prior to the first study treatment, including but not limited to complications of infection, bacteremia or severe pneumonia
• Signs or symptoms of infection within 2 weeks prior to the first study treatment, as assessed by the Investigator
• Received antibiotics for treatment of an infection within 48 hours prior to initiation of study treatment. Subjects receiving prophylactic antibiotics are eligible
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to gemcitabine or nab-paclitaxel
• Any anti-cancer therapy including chemotherapy, hormonal therapy for prostate cancer, or radiotherapy within 2 weeks prior to initiation of study treatment; or herbal therapy intended as anti-cancer therapy within 1 week prior to initiation of study treatment
• Subjects with uncontrolled seizures
• Cardiovascular disease including unstable angina or life-threatening cardiac arrhythmia, myocardial infarction, stroke; or New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) within the last 3 months prior to the first study treatment. Subjects with prior history of Myocardial Infarction (MI), congestive heart failure (CHF), coronary artery bypass grafting, or prior valve surgery need to have assessment of ejection fraction (EF) to ensure EF is not ≤ 40% (as determined by MRI, ECHO, or Nuclear Scan), within the last 3 months prior to the initiation of study treatment
• Other severe concurrent disease or comorbidities which make it difficult to participate in this study, as assessed by Investigator
• Any of the following procedures prior to initiation of study treatment:
• Catheterization, endoscopy, stent or drain placement within 48 hours. (Diagnostic laparoscopy without surgical intervention and/or port placement do not require any wait time prior to study treatment)
• Minor surgery requiring light sedation (such as surgical laparoscopy) within 2 weeks
• Major surgery within 4 weeks
• Women who are breastfeeding
• Male or female subjects of reproductive potential who do not agree to either remain abstinent or employ highly effective and acceptable forms of contraception throughout their participation in the study and for 6 months after the last study treatment
• Subjects receiving any other investigational agents within 2 weeks prior to the initiation of treatment
• Any social situations or psychiatric illness that would limit compliance with study requirements
• Subjects unable or unwilling to have standard catheterization procedure
Transcatheter Mitral Valve Replacement With the Medtronic Intrepid™ TMVR System in Patients With Severe Symptomatic Mitral Regurgitation. (APOLLO)
Multi-center, global, prospective, non-randomized, interventional, pre-market trial. All
subjects enrolled with receive the study device.
studyfinder@utsouthwestern.edu
ALL
18 Years and over
NA
This study is NOT accepting healthy volunteers
NCT03242642
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
* Moderate to severe or severe symptomatic mitral regurgitation
* Local site multidisciplinary heart team experienced in mitral valve therapies agrees that the subject is unsuitable for treatment with approved transcatheter repair or conventional mitral valve intervention
Exclusion Criteria:
* prior transcatheter mitral valve procedure with device currently implanted
* anatomic contraindications
* prohibitive mitral annular calcification
* left ventricular ejection fraction \<25%
* need for emergent or urgent surgery
* hemodynamic instability
DEVICE: Medtronic Intrepid Transcatheter Mitral Valve Replacement System (TMVR), DEVICE: Medtronic Intrepid Transcatheter Mitral Valve Replacement System (TMVR)
A 5-year Longitudinal Observational Study of Patients Undergoing Therapy for Inflammatory Bowel Disease (TARGET-IBD)
TARGET-IBD is a 5-year, longitudinal, observational study of adult and pediatric patients
(age 2 and above) being managed for Inflammatory Bowel Disease (IBD) in usual clinical
practice. TARGET-IBD will create a research registry of patients with IBD within academic and
community real-world practices in order to assess the safety and effectiveness of current and
future therapies.
studyfinder@utsouthwestern.edu
ALL
2 Years and over
This study is NOT accepting healthy volunteers
NCT03251118
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Adults and children (age 2 or older) with a diagnosis of Crohn's disease (CD), Ulcerative colitis (UC), or Indeterminate colitis (IBDU) having been prescribed any IBD treatment (initial or subsequent) outside of a clinical trial.
• Have plans for future visits at the site for continued management of IBD.
Exclusion Criteria:
• Inability to provide written informed consent/assent.
• Being enrolled in any interventional study or trial for IBD treatment. Note: Patient may be enrolled in other registries or studies where IBD treatment outcomes are observed and/or reported (such as center-based registries).
• Prior total abdominal colectomy for UC or IBDU.
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients
with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic
alterations that have come back (recurrent) or does not respond to treatment (refractory) and
may have spread from where it first started to nearby tissue, lymph nodes, or distant parts
of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth.
Call 214-648-5005 studyfinder@utsouthwestern.edu
ALL
12 Months to 21 Years old
PHASE2
This study is NOT accepting healthy volunteers
NCT03213652
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
* Patient must have enrolled onto APEC1621SC//NCI-2017-01251 and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F/NCI-2017-01243 based on the presence of an actionable mutation as defined in APEC1621SC/ NCI-2017-01251
* Patients must be \>= than 12 months and =\< 21 years of age at the time of study enrollment.
* Patients must have a body surface area \>= 0.5 m\^2 at enrollment
* Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on a standard MRI or CT
* Note: The following do not qualify as measurable disease:
* Malignant fluid collections (e.g., ascites, pleural effusions)
* Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
* Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
* Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
* Previously radiated lesions that have not demonstrated clear progression post radiation
* Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
* Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: \>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts \[ANC\] counts): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 42 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial none marrow (BM) radiation
* Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to ensartinib; prior treatment with other ALK inhibitors is permitted given that at least 5 half-lives or 21 days have elapsed since therapy discontinuation, whichever is greater
* For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3 (within 7 days prior to enrollment)
* Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female
* Age 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female
* Age 6 to \< 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female
* Age 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL for female
* Age 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL for female
* Age \>= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for female
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)
* Serum albumin \>= 2 g/dL (within 7 days prior to enrollment)
* Patients must be able to swallow intact capsules
* All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment and for one week after the last dose of ensartinib
* Concomitant medications
* Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Investigational drugs: patients who are currently receiving another investigational drug are not eligible
* Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
* Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* CYP3A4 agents: patients who are currently receiving drugs that are strong inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study
* Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Ensartinib, OTHER: Laboratory Biomarker Analysis, PROCEDURE: Magnetic Resonance Imaging, OTHER: Pharmacological Study, PROCEDURE: Positron Emission Tomography, PROCEDURE: Radionuclide Imaging, PROCEDURE: X-Ray Imaging
Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer
This randomized phase III trial studies digital tomosynthesis mammography and digital
mammography in screening patients for breast cancer. Screening for breast cancer with
tomosynthesis mammography may be superior to digital mammography for breast cancer screening
and may help reduce the need for additional imaging or treatment.
* Women of childbearing potential must not be known to be pregnant or lactating
* Patients must be scheduled for, or have intent to schedule, a screening mammogram
* Patients must be able to tolerate digital breast tomosynthesis and full-field digital mammographic imaging required by protocol.
* Patients must be willing and able to provide a written informed consent
* Patients must not have symptoms or signs of benign or malignant breast disease (eg, nipple discharge, breast lump) warranting a diagnostic rather than a screening mammogram, and/or other imaging studies (eg, sonogram); patients with breast pain are eligible as long as other criteria are met
* Patients must not have had a screening mammogram within the last 11 months prior to date of randomization
* Patients must not have previous personal history of breast cancer including ductal carcinoma in situ
* Patients must not have breast enhancements (e.g., implants or injections)
* ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK
* To be eligible for inclusion in the annual screening regimen one of the following three conditions must be met in addition to the eligibility criteria above:
* Patients are pre-menopausal; OR
* Post-menopausal aged 45-69 with any of the following three risks factors:
* Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
* Family history of breast cancer (first degree relative with breast cancer), or, positive genetic testing for any deleterious genes that indicate an increased risk for breast cancer, or
* Currently on hormone therapy; OR
* Post-menopausal ages 70-74 with either of the following two risk factors:
* Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
* Currently on hormone therapy
* Postmenopausal women are defined as those with their last menstrual period more than 12 months prior to study entry; for the purpose of defining menopausal status for women who have had surgical cessation of their periods, women who no longer have menses due to hysterectomy and oophorectomy will be considered postmenopausal; women who no longer have menses due to hysterectomy without oophorectomy will be considered premenopausal until age 52 and postmenopausal thereafter
* All other postmenopausal women are eligible for inclusion in the biennial screening regimen
* For those women who cannot be assigned to annual or biennial screening at the time of study entry and randomization because they are postmenopausal, have no family history or known deleterious breast cancer mutation, are not on hormone therapy AND have not had a prior mammogram, breast density will be determined by the radiologist?s recording of it at the time of interpretation of the first study screening examination, either DM or TM; for those who are randomized to TM, radiologists will assign BI-RADS density through review of the DM or synthetic DM portion of the TM examination; such women cannot be part of the planned stratification by screening frequency and are expected to represent far less than 1% of the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) population
* Breast density will be determined by prior mammography reports, when available; all other risk factors used to determine patient eligibility for annual or biennial screening will be determined by subject self-report
PROCEDURE: Digital Mammography, PROCEDURE: Digital Tomosynthesis Mammography, OTHER: Laboratory Biomarker Analysis
Breast Screening
Digital Mammography, Breast Tomography, Screening Mammography, TMIST
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability,
pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as
LOXO-292) administered orally to participants with advanced solid tumors, including
rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer
(MTC) and other tumors with RET activation.
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not
candidates for or would be unlikely to tolerate or derive significant clinical benefit
from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is
achieved, evidence of RET gene alteration in tumor and/or blood is required as
identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as
appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance
Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years)
with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months
For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for
their tumor type and stage of disease, or in the opinion of the Investigator, would be
unlikely to tolerate or derive clinical benefit from appropriate standard of care
therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene
alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate
to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with
neuroendocrine features/differentiation, or poorly differentiated thyroid cancers
with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor
sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who
discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET
fusion; determined to be medically operable and tumor deemed resectable by a thoracic
surgical oncologist, without prior systemic treatment for NSCLC
Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants
otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET
inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy,
immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5
half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292
(selpercatinib). In addition, no concurrent investigational anti-cancer therapy is
permitted Note: Potential exception for this exclusion criterion will require a valid
scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned
start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned
start of LOXO-292 (selpercatinib), with the exception of participants receiving
radiation to more than 30% of the bone marrow or with a wide field of radiation, which
must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the
exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated
spinal cord compression. Participants are eligible if neurological symptoms and CNS
imaging are stable and steroid dose is stable for 14 days prior to the first dose of
LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28
days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or
prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds
(msec)
• Participants with implanted pacemakers may enter the study without meeting QTc
criteria due to nonevaluable measurement if it is possible to monitor for QT
changes.
• Participants with bundle branch block may be considered for study entry if QTc is
appropriate by a formula other than Fridericia's and if it is possible to monitor
for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior
systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment
that is directed by genetic testing works in pediatric patients with solid tumors,
non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one
line of standard systemic therapy and/or for which no standard treatment exists that has been
shown to prolong survival. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit
more from treatment which targets their tumor's particular genetic mutation, and may help
doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. langerhans cell histiocytosis \[LCH\], juvenile xanthogranuloma \[JXG\], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus
* Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting 2022): In stage 2 of the study, no tumor samples will be submitted for centralized clinical tumor profiling; instead, a tumor molecular profiling report from a College of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments (CLIA)-approved testing laboratory must be submitted for review by the Molecular Review Committee (MRC)
* This molecular profiling must have been performed on a tumor sample that was obtained at any point after initial tumor recurrence/progression and must be accompanied by a pathology report for the same tumor specimen; a molecular profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that molecular profiling reports are available from multiple timepoints, the most recent report should be prioritized for study submission
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age); note: neurologic deficits in patients with central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have radiographically measurable disease; measurable disease based on imaging obtained less than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
* Note: The following do not qualify as measurable disease:
* Malignant fluid collections (e.g., ascites, pleural effusions)
* Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
* Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
* Elevated tumor markers in plasma or CSF
* Previously radiated lesions that have not demonstrated clear progression post radiation
* Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of treatment assignment
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
* Note: The following do not qualify as measurable disease:
* Malignant fluid collections (e.g., ascites, pleural effusions)
* Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
* Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
* Elevated tumor markers in plasma or CSF
* Previously radiated lesions that have not demonstrated clear progression post radiation
* Leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
* Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive: for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment \>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts \[ANC\]): \>= 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell infusions (with or without total-body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 42 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells, etc.)
* X-ray therapy (XRT)/External Beam Irradiation including Protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): \>= 42 days after systemically administered radiopharmaceutical therapy
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3
* Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: 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: 1 to \< 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
* Age: 2 to \< 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
* Age: 6 to \< 10 years; maximum serum creatinine (mg/dL): male 1; female 1
* Age: 10 to \< 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
* Age: 13 to \< 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
* Age: \>= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase (SGPT) (alanine transferase \[ALT\]) =\< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
Exclusion Criteria:
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
* Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
* Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
* Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols
DSC-MRI in Measuring rCBV for Early Response to Bevacizumab in Patients With Recurrent Glioblastoma
This phase II trial studies how well dynamic susceptibility contrast-enhanced magnetic
resonance imaging (DSC-MRI) works in measuring relative cerebral blood volume (rCBV) for
early response to bevacizumab in patients with glioblastoma that has come back. DSC-MRI may
help evaluate changes in the blood vessels within the cancer to determine a patient?s
response to treatment.
* Histologically proven intracranial glioblastoma or gliosarcoma at initial surgery
* Patients will be eligible if the original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made (high-grade transformation)
* Karnofsky performance status \>= 70
* Women must not be pregnant or breast-feeding
* Progression of disease assessed by local site using Revised Assessment in Neuro-Oncology (RANO) criteria, with plan to give whole-dose bevacizumab therapeutically, either as single therapy or in conjunction with other chemotherapeutic regimens; patients getting bevacizumab to support additional radiation therapy or immunotherapy, or primarily for reduction of edema rather than for tumor treatment, are excluded; this must be the patient?s initial recurrence
* Patient must not have been treated previously with immunotherapies (vaccines, checkpoint inhibitors, T-cells)
* Intratumoral hemorrhage (acute, subacute, or chronic) as seen on hemosiderin-sensitive (gradient-echo) MRI may preclude patient inclusion because of anticipated limited evaluation due to magnetic susceptibility artifact on the heavily T2-weighted DSC-MRI images; if the region of enhancing tumor not affected by blooming artifact on the hemosiderin-sensitive images does not meet the 10 x 10 x 10 mm ?measurable enhancement? threshold specified elsewhere, the patient is ineligible
* Progressive enhancement (\> 25% increase in contrast enhancing volume compared to nadir) on MRI within 14 days of registration, \>= 42 days since completion of radiation/temozolomide therapy, and \>= 28 days since surgical resection or cytotoxic chemotherapy; measurable enhancement is defined as two perpendicular in-plane diameters of at least 10 mm and at least 10 mm in the 3rd orthogonal direction
* Patients must be able to tolerate brain MRI scans with dynamic intravenous gadolinium-based contrast agent injections
* Ability to withstand 22 gauge intravenous (IV) placement
* No history of untreatable claustrophobia
* No magnetic resonance (MR) incompatible implants/devices or metallic foreign bodies
* No contraindication to intravenous contrast administration
* Adequate organ function, including adequate renal function defined as estimated glomerular filtration rate (eGFR) \>= 40 mL/min/1.73 m\^2 as calculated per institution standard of care, and meeting local site requirements for intravenous administration of gadolinium-based MRI contrast agents
* No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
* Weight compatible with limits imposed by the MRI scanner table
* Patient must be scheduled to receive treatment with a standard dose regimen of bevacizumab (bevacizumab infusion on days 1 and 15 of a 28-day treatment cycle); patient can be treated with bevacizumab alone or in combination with other chemotherapies
Exclusion Criteria:
(see Inclusion Criteria)
DIAGNOSTIC_TEST: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the
maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose
(RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an
ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction.
Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded
Independent Central Review (BICR) of repotrectinib in each subject population expansion
cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene
rearrangement. The secondary objective will include the duration of response (DOR), time to
response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit
rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a
ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic
solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on
Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by
protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only
measurable disease as defined by RECIST version 1.1 is allowed.
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer
therapy to National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic
leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol
specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils
count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L);
Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine
clearance Within normal limits or > 40 mL/min; Total serum bilirubin < 1.5 × ULN;
Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present
Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are
present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or
without supplementation
• Life expectancy ≥ 3 months.
PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic
solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene
fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based
local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction
(qPCR) test will be accepted to determine molecular eligibility.
• Adequate tumor tissue needs to be sent to the Sponsor designated central
diagnostic laboratory for retrospective confirmation by a central diagnostic
laboratory test selected by the Sponsor.
OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of
fusion status by a central diagnostic laboratory test selected by the Sponsor
PRIOR to enrollment will be accepted to determine molecular eligibility.
• Adequate tumor tissue must be sent to the Sponsor designated central
diagnostic laboratory for prospective confirmation by a central diagnostic
laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional
ethics committee-approved Informed Consent or an Assent signed by a parent or legal
guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed
by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to
enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST
(v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3
rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all
inclusion and exclusion criteria are met.
i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based
chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv.
EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+
solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic
leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol
specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils
count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L);
Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine
clearance > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases
(ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline
phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present;
Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without
supplementation
• Life expectancy ≥ 3 months.
Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the
skin, or any in situ carcinoma that has been completely resected, requiring therapy
within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy
(except palliative to relieve bone pain) within 2 weeks of study entry. Palliative
radiation (≤10 fractions) must have been completed at least 48 hours prior to study
entry
• Clinically significant cardiovascular disease (either active or within 6 months prior
to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery
bypass graft, symptomatic congestive heart failure (New York Heart Association
Classification Class ≥ II), cerebrovascular accident or transient ischemic attack,
symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac
dysrhythmias of NCI CTCAE grade ≥2
• Any of the following cardiac criteria:
Mean resting corrected QT interval (ECG interval measured from the onset of the QRS
complex to the end of the T wave) for heart rate (QTcF) > 470 msec obtained from 3
ECGs, using the screening clinic ECG machine-derived QTc value Any clinically
important abnormalities in rhythm, conduction or morphology of resting ECG (e.g.,
complete left bundle branch block, third degree heart block, second degree heart
block, PR interval > 250 msec) Any factors that increase the risk of QTc prolongation
or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT
syndrome, family history of long QT syndrome, or any concomitant medication known to
prolong the QT interval.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut
syndrome) or other malabsorption syndromes that would impact drug absorption.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4
interstitial fibrosis or interstitial lung disease including a history of pneumonitis,
hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease,
obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior
radiation pneumonitis are not excluded.
MILD® Percutaneous Image-Guided Lumbar Decompression: A Medicare Claims Study
studyfinder@utsouthwestern.edu
ALL
18 Years to old
This study is NOT accepting healthy volunteers
NCT03072927
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
* Medicare beneficiaries receiving MILD or interspinous process decompression
* Diagnosis of LSS with NC
Exclusion Criteria:
* Patients that have received a laminectomy, laminotomy, fusion, interspinous process decompression, or MILD in the lumbar region during the 12 months prior to the index date
DEVICE: MILD
Lumbar Spinal Stenosis
Lumbar Spinal Stenosis, Interspinous process decompression, MILD, Medicare, Medicare Advantage
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
This phase III trial studies how well active surveillance help doctors to monitor subjects
with low risk germ cell tumors for recurrence after their tumor is removed. When the germ
cell tumor has spread outside of the organ in which it developed, it is considered
metastatic. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, 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. The trial studies
whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic
standard risk germ cell tumors.
* There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT \[all sites\])
* Standard risk 1: Patients must be \< 11 years of age at enrollment
* Standard risk 2: Patients must be \>= 11 and \< 25 years of age at enrollment
* Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment except for those who were initially diagnosed with stage I non-seminoma malignant GCT and later recur during observation post surgery off study; for these patients, if elevated tumor markers rise to \> 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is not required for enrollment
* Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB; grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT); tumor markers: alpha-FP =\< 1,000 ng/mL, beta-HCG institutional normal; all ages
* Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
* Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
* Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus Classification \[IGCCC\] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \< 11
* Standard risk 2 (SR2)
* Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \>= 11 and \< 25
* Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op: alpha-FP \< 1,000 ng/mL, beta-HCG \< 5,000 IU/mL and lactate dehydrogenase (LDH) \< 3.0 x normal; age (years) \>= 11 and \< 25
* Site: extragonadal; stage: COG stage II; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \>= 11 and \< 25
* Notes:
* IGCCC criteria only apply to SR2 patients with a testicular primary tumor
* Use post-op tumor marker levels to determine IGCCC risk group
* Stage 1 seminoma patients are not eligible for the standard risk arms of the study
* For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
* Adequate renal function defined as:
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR
* A serum creatinine based on age/gender as follows (within 7 days prior to enrollment): (mg/dL)
* 1 month to \< 6 months male: 0.4 female: 0.4
* 6 months to \< 1 year male: 0.5 female: 0.5
* 1 to \< 2 years male: 0.6 female: 0.6
* 2 to \< 6 years male: 0.8 female: 0.8
* 6 to \< 10 years male: 1 female: 1
* 10 to \< 13 years male: 1.2 female: 1.2
* 13 to \< 16 years: male: 1.5 female: 1.4
* \>= 16 years male: 1.7 female: 1.4
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 days prior to enrollment)
* Peripheral absolute neutrophil count (ANC) \>= 1,000/mm\^3 (within 7 days prior to enrollment) AND
* Platelet count \>= 100,000/mm\^3 (within 7 days prior to enrollment)
* Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
* Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes \[PROs\] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
* \>= 11 and \< 25 years old at enrollment
* Able to fluently speak and read English
* Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
* Followed for cancer or survivorship care at one of the following institutions:
* Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
* Dana Farber/Harvard Cancer Center
* Hospital for Sick Children
* Children's Hospital of Eastern Ontario
* Oregon Health and Science University
* Seattle Children's Hospital
* Yale University
Exclusion Criteria:
* Patients with any diagnoses not listed including:
* Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
* Pure dysgerminoma
* Pure mature teratoma
* Pure immature teratoma COG stage I, grade I
* Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) \>= 1000 ng/mL
* Pure immature teratoma COG stage II - IV or FIGO stage IC to IV
* "Poor risk" GCT (age \>= 11 years old and COG stage IV ovarian, COG stage III or IV EG, or IGCCC intermediate or poor risk testicular), or
* Primary central nervous system (CNS) germ cell tumor
* Germ cell tumor with somatic malignant transformation
* Spermatocytic seminoma
* Patients must have had no prior systemic therapy for the current cancer diagnosis
* Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain \[stage IV disease\] would be considered poor risk and therefore not eligible for this trial)
* Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of the trial
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
Childhood Extracranial Germ Cell Tumor, Malignant Germ Cell Tumor, Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Stage I Ovarian Choriocarcinoma, Stage II Ovarian Choriocarcinoma, Stage III Ovarian Choriocarcinoma, Stage IV Ovarian Choriocarcinoma, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Malignant Ovarian Teratoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Teratoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7
UT Southwestern; Children’s Health; Parkland Health & Hospital System
INTERCEPT Blood System for RBCs Study in Regions at Potential Risk for Zika Virus Transfusion-Transmitted Infections (RedeS)
Stage A: To evaluate the safety and efficacy of red blood cells (RBCs) prepared with the
INTERCEPT Blood System for Red Blood Cells Pathogen Reduction Treatment (PRT) in comparison
to conventional RBCs in patients who require RBC transfusion support.
Stage B: To provide early access to the INTERCEPT pathogen reduction system for RBC in
regions where a substantial proportion of the population has been infected or is at risk of a
transfusion-transmissible infection.
The objectives and design of Stage B will be reassessed on the completion of Stage A, in
consultation with the FDA.
• Age ≥ 4 years.
• Patients who require or are expected to require a transfusion of RBC component(s),
including red cell exchange transfusion
• Signed and dated informed consent form.
• Female patients of child-bearing potential must:
• Have negative serum or urine pregnancy tests prior to study treatment to rule out
pregnancy, and
• Agree to use to use at least one method of birth control that results in a low
failure rate (i.e., less than 1% per year) when used consistently and correctly
such as implants, injectables, combined oral contraceptives, some intrauterine
devices (IUDs), sexual abstinence or vasectomized partner for the duration of
study participation and an additional 28 days.
For 28-day +6-month extension study in chronically transfused patients:
• A diagnosis of a bone marrow failure syndrome requiring repeated RBC transfusion for
congenital or acquired chronic anemia (e.g., sickle cell anemia, thalassemia, other
hemoglobinopathies, myelodysplastic syndrome, aplastic anemia, chemotherapy or stem cell
transplant etc.)
For 28-day +6-month extension study in SCD patients requiring regular repeated RCE.
• Diagnosis of SCD, either HbSS, HbSC or HbSB0 thalassemia, confirmed by Hb
electrophoresis, deoxyribonucleic acid (DNA) analysis or high-performance liquid
chromatography (HPLC)
• Currently participating in an automated RCE transfusion program (for at least 3 months
prior to enrollment) with 3-to-8 week intervals between RCE transfusion episodes
Stage A: Exclusion Criteria
• Confirmed positive baseline serum/plasma antibody specific to IBS RBC (S 303 treated
RBC) as determined by INTERCEPT S 303 antibody screening panel prior to receiving the
first study transfusion
• Pregnant or breast feeding.
• Presence of an RBC warm autoantibody with evidence of active hemolysis.
• Positive DAT as defined below:
• A polyspecific-DAT reaction strength > 2+, or
• A polyspecific-DAT (any strength) in conjunction with pan-reactivity with a
commercial IAT antibody screening panel that precludes the identification of
underlying alloantibodies or indicates the presence of autoantibody.
• Have had an RBC transfusion within 7 days prior to randomization.
• Have received investigational products, including investigational blood products,
pharmacologic agents or imaging materials, within 28 days prior to randomization.
Prior receipt of conventional blood products tested with an investigational NAT test
is not considered ground for exclusion.
• Patients presenting with or expected to have massive hemorrhage (≥10 RBC units within
24 hours) or expected to require massive transfusion protocols. Planned red cell
exchange does not apply.
• Patients who require neonatal transfusions and intrauterine transfusions.
• Pre-existing antibody to RBC antigens that may make the provision of compatible study
RBC components difficult.
• History of transfusion reactions requiring washed RBCs, volume reduced RBC, or RBCs
with additive solution removed.
• Patients with documented IgA deficiency or a history of severe allergic reactions to
blood products.
• For SCD patients to be enrolled into the repeated RCE 28-day +6-month arm of the
study:
• A history of acute chest syndrome in the last 6 months, or hyperhemolysis
syndrome at any time.
• Clinical evidence of splenic hyperfunction or splenic enlargement: ≥18 cm in
longitudinal diameter (diagnosed at the Investigator's discretion according to
the data available, with ultrasound data being preferable).
• Currently receiving chemotherapy for treatment of cancer. Hydroxyurea for SCD is
acceptable if subject has been on stable therapy for 3 months and no changes to
dosage are planned.
• Subject is in active treatment with renal dialysis.
• Any subject for whom a substantial change in the number of RBC components
transfused is anticipated due to anticipated splenectomy, bone marrow transplant,
surgery or other change in clinical status.
• Subject with known G6PD deficiency or requiring treatment with medications that
are known to adversely affect RBC viability or bone marrow function.
Device: INTERCEPT Blood System for Red Blood Cells, Device: Conventional (Control)
Investigation of Rifampin to Reduce Pedal Amputations for Osteomyelitis in Diabetics (VA INTREPID)
The purpose of this research study is to determine if rifampin, an antibiotic (a medicine
that treats infections), is effective in treating osteomyelitis (infection of the bone) of
the foot in diabetic patients. Despite use of powerful antibiotics prescribed over a long
period of time, many diabetic patients remain at a high risk for needing an amputation of
part of the foot or lower leg because the osteomyelitis is not cured. Some small research
studies have shown that addition of rifampin to other antibiotics is effective in treating
osteomyelitis in both diabetics and non-diabetics. However, because few diabetics with
osteomyelitis have been studied, there is no definite proof that it is better than the usual
treatments for diabetic patients. If this study finds that adding rifampin to the usual
antibiotics prescribed for osteomyelitis reduces the risk for amputations, doctors will be
able to more effectively treat many Veteran patients with this serious infection. Improving
treatment outcomes is an important healthcare goal of the VA.
Call 214-648-5005 studyfinder@utsouthwestern.edu
ALL
18 Years to 89 Years old
PHASE4
This study is NOT accepting healthy volunteers
NCT03012529
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Age 18 and 89 years
• Diagnosis of diabetes mellitus, either by: 1) use of oral hypoglycemic agents or insulin at the time of enrollment; 2) a hemoglobin A1c (HgA1c) level within the past 90 days \> 6.5; or 3) a medical record diagnosis of diabetes mellitus by a clinician on two or more occasions in the previous 10 years
• Definite or probable osteomyelitis in the diabetic foot, as defined by the International Working Group on the Diabetic Foot (Table 1). Criteria must be present at some point within 90 days prior to enrollment.
• All planned debridement has been completed prior to randomization.
• A course of backbone antimicrobial therapy has been selected.
Exclusion Criteria:
• Patient unable to receive enteral medication.
• Patient is allergic to or intolerant of rifampin.
• Patient is taking a drug that has interactions with rifampin that would require either stoppage, substitution or an empiric dose modification that may place the patient at medical risk.
• Within 30 days of enrollment, patient is taking immunosuppressive medications to prevent rejection of an organ transplant or is receiving chemotherapy for cancer or molecularly targeted therapies for cancer.
• Patient is receiving antiretroviral therapy for HIV or antiviral medication for Hepatitis C.
• Patient is participating in another interventional clinical trial for which a waiver of dual enrollment with CSP#2001 has not been obtained.
• Patient has an ALT \> 3 times the upper limit of normal for the site laboratory, or total bilirubin \> 2.5 times the upper limit of normal for the site laboratory\*,\*\*\*; INR \> 1.5, OR patient has Child-Pugh Class C Cirrhosis.
• Patient has a baseline white blood cell count (WBC) \<2000 cells/mm3\*\*\* OR absolute neutrophil count (ANC) \<1000 cells/mm3\*\*\* OR platelet count \<50,000 cells/mm3\*\*,\*\*\* OR hemoglobin \<8.0 g/dL.\*\*,\*\*\*.
• Women of child-bearing potential (those with menses within the last year) with a positive serum pregnancy test.
• Patient is believed unlikely to be able to complete the trial due to medical conditions.
• Patient is believed unlikely to complete the trial due to neurologic and psycho-behavioral disorders such as active substance abuse or dependence, disabling dementias or psychoses.
• Patient refuses or is clinically unable to undergo the recommended level of debridement.
• Indwelling hardware present in the foot, at the site of the index osteomyelitis.
• Treatment with antibacterial agents for infection at another site, where the duration of treatment is anticipated to be greater than 14 days.
• Patient is receiving therapy for COVID-19 that interacts with rifampin.
* Patients with total bilirubin \> 2 times the ULN who have Gilbert's Disease or any other inherited disease affecting bilirubin metabolism without meeting other exclusionary criteria, may be considered for inclusion in the study.
* Patients with platelet count \<50,000 cells/mm3 due only to hypersplenism and meeting no other exclusionary criteria may be considered for inclusion in the study.
* If multiple laboratory values are available, the most recent value will be applied for eligibility.
Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, the COMMIT Study
This phase III trial studies how well combination chemotherapy, bevacizumab, and/or
atezolizumab work in treating patients with deficient deoxyribonucleic acid (DNA) mismatch
repair colorectal cancer that has spread from where it first started (primary site) to other
places in the body (metastatic). Chemotherapy drugs, such as fluorouracil, oxaliplatin, and
leucovorin calcium, 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.
Bevacizumab may stop or slow colorectal cancer by blocking the growth of new blood vessels
necessary for tumor growth. Immunotherapy with monoclonal antibodies, such as atezolizumab,
may help the body's immune system attack the cancer, and may interfere with the ability of
tumor cells to grow and spread. Giving combination chemotherapy, bevacizumab, and
atezolizumab may work better in treating patients with colorectal cancer.
* The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer except for one cycle of FOLFOX or capecitabine and oxaliplatin (CAPOX), either with or without bevacizumab prior to enrollment. Upon enrollment, the preceding single cycle of FOLFOX or FOLFOX + bevacizumab, if the patient received one, will not count towards patients' assessments per protocol. Cycle 1 day 1 (C1D1) of atezolizumab or C1D1 of mFOLFOX6/bevacizumab + atezolizumab will correspond to the first day the patient received therapy on trial
* Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; alternatively, MSI-H diagnosed by polymerase chain reaction (PCR)-based assessment of microsatellite alterations (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) are eligible
* Documentation by PET/CT scan, CT scan, or MRI that the patient has measurable metastatic disease per RECIST 1.1
* No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass
* Absolute neutrophil count (ANC) must be \>= 1500/mm\^3 (obtained within 28 days prior randomization)
* Platelet count must be \>= 100,000/mm\^3 (obtained within 28 days prior randomization)
* Hemoglobin must be \>= 8 g/dL (obtained within 28 days prior randomization)
* Total bilirubin must be =\< 4 x ULN (upper limit of normal) (obtained within 28 days prior randomization); and
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =\< 3 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be =\< 5 x ULN (obtained within 28 days prior randomization)
* Calculated creatinine clearance \>= 30 mL/min (obtained within 28 days prior randomization)
* A urine sample tested for proteinuria by either the dipstick method, urinalysis (UA), or a urine protein creatinine (UPC) ratio:
* The dipstick method must indicate 0-1+ protein; if dipstick reading is \>= 2+, a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours or a UPC ratio \< 1.0
* A urine protein creatinine (UPC) ratio must be \< 1.0; if the UPC ratio is \>= 1.0 a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours
* Urinalysis must indicate \< 30 mg/dl. If urinalysis \>= 30 mg/dl, a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours or a UPC ratio \< 1.0
* International normalized ratio of prothrombin time (INR) and prothrombin time (PT) must be =\< 1.5 x ULN for the lab within 28 days before randomization; patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history, regardless of PT/INR results
* Pregnancy test done within 28 days prior randomization must be negative (for women of childbearing potential only); pregnancy testing should be performed according to institutional standards; administration of atezolizumab or mFOLFOX6/bevacizumab/atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; 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
* Women of child-bearing potential and men must agree to use adequate contraception methods that result in a failure rate of \< 1% per year during the treatment period (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, and 6 months after the last dose of mFOLFOX6; a woman is considered to be of childbearing potential if she is not postmenopausal, has not reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus); examples of contraceptive methods with a failure rate of \< 1% per year include: bilateral tubal ligation; male partner sterilization; intrauterine devices; the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception; men must refrain from donating sperm during this same period
Exclusion Criteria:
* Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, fluoropyrimidines, folic acid derivatives or oxaliplatin
* Uncontrolled high blood pressure defined as systolic blood pressure (BP) \> 150 mmHg or diastolic BP \> 100 mmHg with or without anti-hypertensive medication; patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria
* Documented New York Heart Association (NYHA) class III or IV congestive heart failure
* Serious or non-healing wound, skin ulcer, or bone fracture
* History of inherited bleeding diathesis, gastrointestinal (GI) perforation, significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis or symptomatic peripheral ischemia, transient ischemic attack \[TIA\], cerebrovascular accident \[CVA\] or arterial thrombotic event), abdominal fistula, intra-abdominal abscess, or active GI bleeding (with cause not addressed) within 6 months prior to randomization, or other medical condition in the opinion of the treating oncologist that makes the risk of cardiovascular or bleeding complications with bevacizumab use unacceptably high
* Other malignancies are excluded unless the patient has completed therapy for the malignancy \>= 12 months prior to randomization and is considered disease-free; patients with the following cancers are eligible if diagnosed and treated within the past 12 months: in situ carcinomas or basal cell and squamous cell carcinoma of the skin
* Known DPD (dihydro pyrimidine dehydrogenase) deficiency
* Symptomatic peripheral sensory neuropathy \>= grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
* Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization
* History of grade 2 hemoptysis (defined as 2.5 mL of bright red blood per episode) within 1 month prior to screening
* Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents; patients who have received prior treatment with anti-CTLA-4 may be enrolled provided the following requirements are met:
* Minimum of 12 weeks from the first dose of anti-CTLA-4 and \> 6 weeks from the last dose to randomization
* No history of severe immune-related adverse effects (CTCAE grade 3 and 4) from anti-CTLA-4
* Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 14 days prior to randomization; however,
* Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily treatment with corticosteroids with a dose of =\< 10 mg/day methylprednisolone equivalent) may be enrolled
* The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease; however,
* Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HbsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible if polymerase chain reaction (PCR) for hepatits B virus (HBV) ribonucleic acid (RNA) is negative per local guidelines
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA per local guidelines
* History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis; however,
* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
* Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
* Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
* Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
* Rash must cover less than 10% of body surface area (BSA)
* Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
* History of idiopathic pulmonary fibrosis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or active or recently active (within 90 days of randomization) pneumonitis (including drug induced) that required systemic immunosuppressive therapy (i.e. corticosteroids, etc.). History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Patients with known active tuberculosis (TB) are excluded
* Severe infections within 28 days prior to randomization, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of infection within 14 days prior to randomization
* Received oral or intravenous (IV) antibiotics within 14 days prior to randomization; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
* The administration of a live, attenuated vaccine within 28 days prior to randomization
* Pregnant women are excluded from this study because atezolizumab is an 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 atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab; these potential risks may also apply to other agents used in this study; (Note: pregnancy testing should be performed within 28 days prior to randomization according to institutional standards for women of childbearing potential)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
DExterous Hand Control Through Fascicular Targeting (DEFT) - (Human Subjects)
Our goal is to temporarily implant the following groups for 540 +/- 30 days:
1. Forearm FAST electrodes
1. Five human partial hand amputees (amputated at the level of the hand) with 2 FAST
electrodes in the ulnar nerve and 2-5 FAST electrodes in the median nerve.
2. Five human hand and forearm amputees (amputated at the level of the forearm) with 2
FAST electrodes in the ulnar nerve and 2-5 FAST electrodes in the median nerve .
2. Arm FAST electrodes
1. Five human partial hand amputees (amputated at the level of the hand) with 2 FAST
electrodes in the ulnar nerve and 2-5 FAST electrodes in the median nerve.
2. Five human hand and forearm amputees (amputated at the level of the forearm) with 2
FAST electrodes in the ulnar nerve and 2-5 FAST electrodes in the median nerve.
3. Five human hand, forearm and arm amputees (amputated at the level of the arm) with
2 FAST electrodes in the ulnar nerve and 2-5 FAST electrodes in the median nerve.
Criteria for Inclusion of Subjects:
Hand, forearm and arm amputees:
• Male or female, age 18 and older, of any race or ethnicity
• Able and willing to sign Consent
• Able and willing to participate in all study activities including implantation,
testing and explantation of the study device.
• Able to communicate effectively in English without an interpreter
After preliminary screening subjects will be assessed for the following inclusion criteria:
Overall and phantom pain are well-controlled and not incapacitating
Criteria for Exclusion of Subjects:
• If MR neurogram and EMG/NCS study show nerve or muscle dysfunction/injury at a higher
level than anticipated based on the appearance of the physical amputation stump, the
subject may be excluded from the study due to adverse neuromuscular anatomy which
would preclude use of the proposed experimental electrode implants. The radiographs
will be used to confirm suitability of the amputation stump configuration. If the bony
anatomy of the amputation stump is found to be unsuitable, the patient may be excluded
from the study.
• Subjects who have a history of cardiac arrhythmia will be excluded from the study.
Other: Fast electrode
Amputation, Traumatic, Hand, Brain and Nervous System
peripheral nerve, intraneural electrode, hand amputation, forearm amputation
Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients
with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come
back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a
monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab
attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill
them.
* Patients must be \>= 1 year and \< 22 years of age at the time of enrollment
* Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with \>= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
* NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
* Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing \>= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
* Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a bright fluorophore such as phycoerythrin \[PE\] is strongly recommended)
* In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be performed due to patient clinical status, flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1,000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
* Patients with one of the following:
* Second or greater relapse;
* Primary refractory disease with at least 2 prior induction attempts;
* First relapse refractory to at least one prior re-induction attempt
* Any relapse after HSCT (Cohort 1 ONLY)
Patients with Down syndrome are eligible ONLY for Cohort 1 with:
* Any of above disease status, OR
* First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or prior HSCT are NOT eligible for Cohort 2 combination therapy
* Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =\< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study. Apply to Cohort 2:
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
* A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).
* A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. For patients who previously received calaspargase pegol, \>= 21 days must have elapsed after the last dose. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
* Note: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy.
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
* Anti-cancer agents that are 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. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
* Radiotherapy: \>= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); \>= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if \>= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; \>= 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
* Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patient must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is allowed.
* Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed from the last CAR-T cell infusion
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* 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:
* 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
* 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
* 6 to \< 10 years: maximum serum creatinine 1 mg/dL (both male and female)
* 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
* 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
* \>= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
* Direct bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L
Exclusion Criteria:
* Patients with any prior history of SOS irrespective of severity
* Patients with isolated central nervous system (CNS), testicular, or any other extramedullary site of relapse
* Patients who have been previously treated with inotuzumab ozogamicin
* Patients who have previously received HSCT (Cohort 2 only)
* Patients with Down syndrome (Cohort 2 only)
* History of allergic reaction attributed to compounds of similar or biologic composition to inotuzumab ozogamicin or other agents in the study
* Note: Patients with history of allergy to pegaspargase/calaspargase pegol are eligible for enrollment on Cohort 2 if Erwinia formulation of asparaginase can be obtained
* Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
* Patients who are currently receiving another investigational drug
* Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy)
* Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD or anti-rejection medications
* Patients who are currently receiving or plan to receive corticosteroids except as described below
* Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, (Cohort 1 only) for all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
* Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient
* Patients who have an active uncontrolled infection defined as:
* Positive bacterial blood culture within 48 hours of study enrollment;
* Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
* Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
* Active viral or protozoal infection requiring IV treatment
* Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome
* There have been no human studies of inotuzumab ozogamicin in pregnant women and no reports of exposure in utero; based on nonclinical safety studies, inotuzumab ozogamicin has the potential to impair human male and female fertility and to adversely affect human embryo fetal development; women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin; there is no information regarding the presence of inotuzumab ozogamicin in human milk, the effects on the breast-fed infant, or the effects on milk production; because of the potential for adverse reactions in breast-fed infants, women should not breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months after the final dose
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment
* Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin
* Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and for at least 5 months after the last dose of inotuzumab ozogamicin
* Lactating females are not eligible unless they agree not to breastfeed their infants
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma
A Longitudinal Observational Study of the Natural History and Management of Patients With HCC
TARGET-HCC is a longitudinal, observational study of patients being managed for HCC in usual
clinical practice. TARGET-HCC will create a research registry of participants with HCC within
academic and community real-world practices in order to assess the safety and effectiveness
of the entire spectrum of current and future therapies across diverse populations.
Call 214-648-5005 studyfinder@utsouthwestern.edu
ALL
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT02954094
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Male or female patients, age ≥18 years
• Patients with a histological/cytological or radiological diagnosis of HCC (mixed HCC cholangiocarcinoma may be included; patients who are candidates for surgical and non-surgical treatment, as well as those being followed without specific HCC therapy may be included)
Dallas 2K: A Natural History Study of Depression (D2K)
The Dallas 2K is a 10-year natural history, longitudinal, prospective study of a cohort of
2,000 participants that will help uncover the socio-demographic, lifestyle, clinical,
psychological and neurobiological factors that contribute to anti-depressant treatment
response: remission, recurrence, relapse and individual outcomes in depressive disorders.
Hence, the expected duration of this study is 20 years in length. Since this is an
observational study, investigators will explore a comprehensive panel of carefully selected
participant specific parameters: socio-demographic (age, ethnicity, economic); lifestyle
(physical activity, substance use); clinical (medical history, anxious depression, early life
trauma), biological (biomarkers in blood, saliva, urine), behavioral (cognitive, emotional),
neurophysiological (EEG), and neuroimaging (structural, functional brain circuitry) with the
goal to develop the most robust predictive models of treatment response and of depression
outcomes. There is no medication or non-medication treatment or intervention provided by this
study.
Subjects will have elevated symptomatology of nonpsychotic chronic or recurrent depressive
disorder and will be currently receiving or will be prescribed standard of care medication or
non-medication based treatments by their providers/clinicians. The study cohort will reflect
the wide range of patients seen in typical primary or psychiatric care settings, and may
include unipolar or bipolar disorders and dysthymia (a more chronic form of depression). The
cohort will be broadly representative of and generalizable to the US general population as a
whole.
Criteria for Inclusion of participants:
A potential participant will be eligible for participation in this study if the following criteria are met:
• Male and female adult or youth aged 10 and older of any race or ethnicity.
• Ability to speak, read, and understand English. However, the parent(s) or legal guardians of minors may either speak English or Spanish as the consenting process can be conducted bilingually.
• A lifetime or a current diagnosis of a mood disorder based upon a semi-structured diagnostic interview.
• Adults age 18 and older must be able to provide written informed consent; for youth younger than age 18, a parent or legal guardian must provide written informed consent, and the child or teen must provide written informed assent.
Eligibility for Healthy Controls
For comparison purposes, potential health control participants who do NOT have a psychiatric diagnosis will be enrolled as part of the healthy control arm of this study.
• Male and female adult or youth aged 10 and older of any race or ethnicity.
• Ability to speak, read, and understand English. However, the parent(s) or legal guardians of minors may either speak English or Spanish as the consenting process can be conducted bilingually.
• Adults age 18 and older must be able to provide written informed consent; for youth younger than age 18, a parent or legal guardian must provide written informed consent, and the child or teen must provide written informed assent.
Criteria for Exclusion of Participants
A potential participant will NOT be eligible for participation in this study if any of the following criteria are met:
• History of schizophrenia, schizoaffective disorders or chronic psychotic disorders based upon a semi-structured diagnostic interview.
• Diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C (human immunodeficiency virus (HIV) testing is not required for this study).
• Unable to provide a stable home address and contact information.
• Has any condition for which, in the opinion of the investigator or designee, study participation would not be in their best interest (including but not limited to cognitive impairment, unstable general medical condition, intoxication, active psychosis) or that could prevent, limit, or confound the protocol-specified assessments.
• Requires immediate hospitalization for psychiatric disorder or suicidal risk as assessed by a licensed study clinician.
Eligibility for Healthy Controls
A potential Healthy Control participant will NOT be eligible for participation in this study if any of the following criteria are met:
• A lifetime or a current history of a mood disorder based upon a semi-structured diagnostic interview.
• Meets any exclusion criteria as part of the main D2K study interview.
OTHER: Observational Study
Depression, Depression, Bipolar
UT Southwestern; Children’s Health; Parkland Health & Hospital System