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Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma (EMERGE 101)
This study is conducted in two phases. The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin monotherapy in pediatric participants with previously treated solid tumors. This is followed by the phase 2 portion, to further assess the effectiveness and safety in pediatric and young adult participants with recurrent/refractory Ewing sarcoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
2 Years to 30 Years old
PHASE1
NCT05734066
STU-2023-0156
Key
Inclusion Criteria:
Age
* Participant must meet the following age requirements at the time the informed consent form (ICF) (and assent form, if applicable) is signed:
* Phase 1 Part 1: participants must be ≥ 2 to \< 18 years of age.
* Phase 1 Part 2: participants must be ≥ 2 to ≤ 30 years of age.
* Phase 2: participants must be ≥ 2 to ≤ 30 years of age.
Type of Participant and Disease Characteristics
* Participant has a confirmed solid tumor
* The participant has a Lansky/Karnofsky performance status score of ≥ 50%.
* The participant has adequate liver function, evidenced by the following laboratory values:
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN).
* Total bilirubin ≤ 1.5 × institutional ULN (with the exception of participants with Gilbert's syndrome who must have bilirubin \< 3 × institutional ULN).
* The participant has adequate bone marrow function, evidenced by the following:
* Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (independent of growth factor support within 1 week of screening laboratories).
* Platelets ≥ 100 × 109/L (without platelet transfusion within previous 7 days of screening laboratories).
* Hemoglobin ≥ 8 g/dL (note: may have been transfused).
* The participant has an adequate renal function:
* Calculated creatinine clearance (use Cockcroft-Gault formula for participants ≥ 18 years; Schwartz equation for participants \< 18 years) ≥ 60 mL/min.
* The participant has an adequate cardiac function:
* Left ventricular ejection fraction or shortening fraction per institutional norm ≥ institutional lower level of normal.
* The participant has creatine phosphokinase ≤ 2.5 × institutional ULN.
Weight
* The participant has body weight ≥ 15 kg.
Sex and Contraceptive/Barrier Requirements
Male participants:
Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 4 months after the last dose of study intervention:
* Refrain from donating sperm.
PLUS, either:
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR
* Must agree to use contraception/barrier as detailed below:
* Agree to use a male condom with female partner and use of an additional highly effective contraceptive method with a failure rate of \< 1% per year when having sexual intercourse with a Woman of childbearing potential (WOCBP) who is not currently pregnant.
* Note: male participants who are azoospermic (vasectomized or due to a medical cause) are still required to follow the protocol-specified contraception/barrier criteria.
Female participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
* Is a Woman of nonchildbearing potential (WONCBP). OR
* Is a WOCBP and using an acceptable contraceptive method during the study intervention period (at least 7 months after the last dose of study intervention). The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 7 days before the first dose of study intervention.
* If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
* Additional requirements for pregnancy testing during and after study intervention.
* The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Informed Consent
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Key Exclusion Criteria:
Medical Conditions
* corrected QT interval (QTc) prolongation defined as a QTc ≥ 470 ms using the Bazett formula.
* Known symptomatic Central nervous system (CNS) metastases requiring steroids. Participants with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to enrollment, have discontinued high dose steroid treatment for these metastases for at least 2 weeks, and are neurologically stable (physiologic doses of steroids and short courses of steroids for other indications are acceptable).
* Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy, hypothyroidism, and rash Grade ≤ 2 are acceptable, and other Grade ≤ 2 adverse events (AEs) not constituting a safety risk based on the investigator's judgement are acceptable.
* An uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with participation in this study.
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high-risk for treatment complications.
Prior/Concomitant Therapy
* Received prior treatment with lurbinectedin or trabectedin.
* Received prior treatment with any investigational product within 4 weeks of first infusion of study intervention. Observational studies are permitted.
* Received live or live attenuated vaccines within 4 weeks of the first dose of study treatment or plans to receive live vaccines during study participation. Administration of inactive vaccines or messenger ribonucleic acid (mRNA) vaccines (for example, inactivated influenza vaccines or COVID-19 vaccines) are allowed.
* Had major surgery ≤ 4 weeks or radiation therapy ≤ 2 weeks prior to enrollment unless fully recovered. Prior palliative radiotherapy is permitted, provided it was completed at least 2 weeks prior to participant enrollment.
* Received prior allogeneic bone marrow transplantation or solid organ transplant.
* Received chemotherapy ≤ 3 weeks prior to start of study intervention.
Diagnostic Assessments
* Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or Polymerase chain reaction (PCR) test for HCV RNA if HCV antibody test is positive).
* Human immunodeficiency infection at screening (positive anti-HIV antibody).
Other Exclusions
* Has a known or suspected hypersensitivity to any of the components of the study intervention.
* The participant or parent(s)/guardian(s) is/are unable to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator DRUG: Lurbinectedin
Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma, Ewing Sarcoma, Sarcoma
Solid Tumors, lurbinectedin, ewing's sarcoma, soft tissue sarcoma, sarcomas
Children’s Health
DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE)
This study is a prospective, multicenter, randomized controlled trial of an interventional strategy using the ClotTriever System to achieve and maintain vessel patency (ClotTriever Intervention Arm) versus conservative medical management using anticoagulation therapy alone (Conservative Medical Management Arm) in the treatment of subjects with symptomatic unilateral iliofemoral DVT. The study will collect data on demographics, comorbidities, details from the DVT diagnosis and treatment, and clinical outcomes through the 6-month follow up visit.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Jarrett.Hubbard@UTSouthwestern.edu
Michael Siah
All
18 Years and over
N/A
NCT05701917
STU-2023-0117
Inclusion Criteria
• Age ≥ 18 years
• Proximal lower extremity unilateral DVT involving at least the common femoral, external iliac, or common iliac veins, alone or in combination
• Symptom onset within 12 weeks of enrollment in the study
• Significant symptoms, as defined by a Villalta score > 9
• Willing and able to provide informed consent Exclusion Criteria
• Bilateral iliofemoral DVT
• Prior venous stent in the target venous segment
• IVC aplasia/hypoplasia or other congenital anatomic anomalies of the IVC or iliac veins
• IVC filter in place at the time of enrollment
• Limb-threatening circulatory compromise (e.g., phlegmasia)
• Clot in transit including IVC thrombus presenting as extension of >2cm into the IVC from the CIV
• Symptomatic PE with right heart strain where the physician judges that a DVT intervention is inappropriate at this time.
• Inability to be a candidate for intervention due to medical or technical reasons based on physician judgement
• Severe allergy, hypersensitivity to, or thrombocytopenia from heparin
• Severe allergy to iodinated contrast agents that cannot be mitigated
• Hemoglobin < 8.0 g/dL, INR > 1.7 before warfarin was started, or platelets < 50,000/µl which cannot be corrected prior to enrollment
• Severe renal impairment (estimated GFR < 30 ml/min) in patients who are not yet on dialysis
• Inability to provide therapeutic anticoagulation per Investigator discretion
• Uncontrolled severe hypertension on repeated readings (systolic > 180mmHg or diastolic > 105mmHg)
• Recently (< 30 days) had DVT interventional procedure
• Subject is participating in another study that may interfere with this study
• Life expectancy < 6 months or chronic non-ambulatory status
• Known hypercoagulable states that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject (e.g., contraindication to use of ClotTriever per local approved labeling, compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments)
• Subject has previously completed or withdrawn from this study
• Patient unwilling or unable to conduct the follow up visits per protocol
• Age ≥ 18 years
• Proximal lower extremity unilateral DVT involving at least the common femoral, external iliac, or common iliac veins, alone or in combination
• Symptom onset within 12 weeks of enrollment in the study
• Significant symptoms, as defined by a Villalta score > 9
• Willing and able to provide informed consent Exclusion Criteria
• Bilateral iliofemoral DVT
• Prior venous stent in the target venous segment
• IVC aplasia/hypoplasia or other congenital anatomic anomalies of the IVC or iliac veins
• IVC filter in place at the time of enrollment
• Limb-threatening circulatory compromise (e.g., phlegmasia)
• Clot in transit including IVC thrombus presenting as extension of >2cm into the IVC from the CIV
• Symptomatic PE with right heart strain where the physician judges that a DVT intervention is inappropriate at this time.
• Inability to be a candidate for intervention due to medical or technical reasons based on physician judgement
• Severe allergy, hypersensitivity to, or thrombocytopenia from heparin
• Severe allergy to iodinated contrast agents that cannot be mitigated
• Hemoglobin < 8.0 g/dL, INR > 1.7 before warfarin was started, or platelets < 50,000/µl which cannot be corrected prior to enrollment
• Severe renal impairment (estimated GFR < 30 ml/min) in patients who are not yet on dialysis
• Inability to provide therapeutic anticoagulation per Investigator discretion
• Uncontrolled severe hypertension on repeated readings (systolic > 180mmHg or diastolic > 105mmHg)
• Recently (< 30 days) had DVT interventional procedure
• Subject is participating in another study that may interfere with this study
• Life expectancy < 6 months or chronic non-ambulatory status
• Known hypercoagulable states that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject (e.g., contraindication to use of ClotTriever per local approved labeling, compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments)
• Subject has previously completed or withdrawn from this study
• Patient unwilling or unable to conduct the follow up visits per protocol
Device: ClotTriever System, Drug: Commercially available/market approved anticoagulation medication including but not limited to: Heparin Sodium, Coumadin, Rivaroxaban, Apixaban, etc.
Venous Thromboembolism, Deep Venous Thrombosis, Post-Thrombotic Syndrome
Venous Thromboembolism, Deep Venous Thrombosis, Post-Thrombotic Syndrome, Anticoagulation, Percutaneous Mechanical Thrombectomy
UT Southwestern
A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)
The purpose of this study is to evaluate the safety and tolerability of olezarsen in participants with SHTG.
Call 214-648-5005
studyfinder@utsouthwestern.edu, CHANDNA.VASANDANI@UTSouthwestern.edu
Zahid Ahmad
All
18 Years and over
Phase 3
NCT05681351
STU-2023-0297
Inclusion Criteria:
• Satisfactory completion of either ISIS 678354-CS5 or ISIS 678354-CS6 (last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgment.
• Participants must be on a stable regimen of lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines.
Exclusion Criteria:
• Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study, including need for treatment with disallowed medications, or need to change the required stable regimen as per either ISIS 678354-CS5 or ISIS 678354-CS6 study entry criteria. NOTE: Other Inclusion/Exclusion criteria may apply.
Drug: Olezarsen
Severe Hypertriglyceridemia
ISIS 678354, Olezarsen
UT Southwestern
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort (INSIGHT)
This is an open-label, multicenter, two-arm Phase II clinical trial that will evaluate the impact of 2nd line chemotherapy (i.e. capecitabine) on survival in patients with non-Luminal A hormone receptor-positive (HR+) metastatic breast cancer (MBC)
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
ALL
18 Years to old
PHASE2
NCT05693766
STU-2023-1153
Inclusion Criteria:
* Signed and dated written informed consent.
* Subjects ≥ 18 years of age.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is:
* ER (\>/=1%) and/or PR (\>/= 1%) by IHC and HER2 negative (by IHC or FISH)
* Previously exposed to an aromatase inhibitor (AI) or a selective estrogenreceptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor.
* Prior radiation permitted (if completed at least 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity (≤ grade 1) induced by this treatment (except for alopecia)
* Patients with brain metastasis secondary to breast cancer and clinically stable for more than 4 weeks from completion of radiation treatment and off steroids
* Evaluable disease (measurable or non-measurable)
* Measurable disease, ie, at least 1 measurable lesion as per RECIST 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation)
* Patients with bone only disease allowed if possible to evaluate on radiological exams (eg.bone scan, PET/CT, CT, MRI) even if lesions are non-measurable according to RECIST1.1.
* Adequate organ function including:
* Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L
* Platelets ≥ 100 × 10\^9/L
* Hemoglobin ≥ 8/g/dL (may have been transfused)
* Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present)
* Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50mL/min as calculated using the Cockcroft-Gault (CG) equation
* For randomized patients only: tumors must be diagnosed as non-Luminal A using the Blueprint® and Mammaprint® tests
Exclusion Criteria:
* Prior chemotherapy in the metastatic setting
* Previous malignant disease other than breast cancer within the last 2 years with associated competing risk, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs AND additional therapy not required while receiving study treatment).
* Persisting symptoms related to prior therapy that has not reduced to Grade 1 \[National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0\]; however, menopausal symptoms, alopecia, and sensory neuropathy Grade ≤ 2 is acceptable
* Pregnant or breastfeeding females. DRUG: Capecitabine, OTHER: Endocrine-therapy, OTHER: MammoPrint ® and BluePrint assays
Invasive Mammary Carcinoma, Metastatic Breast Cancer, Breast - Female
UT Southwestern
A Study to Test Asundexian for Preventing a Stroke Caused by a Clot in Participants After an Acute Ischemic Stroke or After a High-risk Transient Ischemic Attack, a So-called Mini Stroke (OCEANIC-STROKE)
Researchers are looking for a better way to prevent an ischemic stroke which occurs when a blood clot travelled to the brain in people who within the last 72 hours had: * an acute stroke due to a blood clot that formed outside the heart (acute non-cardioembolic ischemic stroke), or * TIA/mini-stroke with a high risk of turning into a stroke (high-risk transient ischemic attack), and who are planned to receive standard of care therapy. Acute ischemic strokes or TIA/mini-stroke result from a blocked or reduced blood flow to a part of the brain. They are caused by blood clots that travel to the brain and block the vessels that supply it. If these blood clots form elsewhere than in the heart, the stroke is called non-cardioembolic. People who already had a non-cardioembolic stroke are more likely to have another stroke. This is why they are treated preventively with an antiplatelet therapy, the current standard of care. Antiplatelet medicines prevent platelets, components of blood clotting, from clumping together. Anticoagulants are another type of medicine that prevents blood clots from forming by interfering with a process known as coagulation (or blood clotting). The study treatment asundexian is a new type of anticoagulant currently under development to provide further treatment options. Asundexian aims to further improve the standard of care without increasing the risk of bleeding. The main purpose of this study is to learn whether asundexian works better than placebo at reducing ischemic strokes in participants who recently had a non-cardioembolic ischemic stroke or TIA/mini-stroke when given in addition to standard antiplatelet therapy. A placebo is a treatment that looks like a medicine but does not have any medicine in it. Another aim is to compare the occurrence of major bleeding events during the study between the asundexian and the placebo group. Major bleedings have a serious or even life-threatening impact on a person's health. Dependent on the treatment group, the participants will either take asundexian or placebo once a day for at least 3 months up to 31 months. Approximately every 3 months during the treatment period, either a phone call or a visit to the study site is scheduled on an alternating basis. In addition, one visit before and up to two visits after the treatment period are planned. During the study, the study team will: * Check vital signs such as blood pressure and heart rate * Examine the participants' heart health using an electrocardiogram (ECG) * Take blood samples * Ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Matalin.Miller@UTSouthwestern.edu
Ty Shang
ALL
18 Years and over
PHASE3
NCT05686070
STU-2023-0001
Inclusion Criteria:
* Participants must be ≥ 18 years of age
* Acute non-cardioembolic stroke or high-risk TIA
* Systemic or cerebrovascular atherosclerosis or acute non-lacunar infarct
Exclusion Criteria:
* Ischemic stroke ≤ 7 days before the index event
* Index stroke following procedures or strokes due to other rare causes
* History of atrial fibrillation/flutter, left ventricular thrombus, mechanic valve or other cardioembolic source of stroke requiring anticoagulation DRUG: Asundexian (BAY2433334), DRUG: Placebo
Prevention of Ischemic Stroke, Acute Non-cardioembolic Ischemic Stroke, High-risk Transient Ischemic Attack, Brain and Nervous System
UT Southwestern
A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab
This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard treatment alone in improving survival in patients with stage I and II classical Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, and procarbazine hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without radiation may increase survival and/or fewer short-term or long-term side effects in patients with classical Hodgkin lymphoma compared to the standard treatment alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Ksenya Shliakhtsitsava
ALL
5 Years to 60 Years old
PHASE3
NCT05675410
STU-2023-0552
Inclusion Criteria:
* Patients must be 5 to 60 years of age at the time of enrollment
* Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified \[NOS\]) with stage I or II disease
* Patients must have bidimensionally measurable disease (at least one lesion with longest diameter \>= 1.5 cm)
* Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained
* Pediatric patients (age 5-17 years) with known or suspected mediastinal disease must have an upright posteroanterior (PA) chest X-ray (CXR) for assessment of bulky mediastinal disease.
* Note: Pediatric patients who have received both a CT chest and upright PA CXR may meet the definition of bulk through either modality.
* Patients \>= 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2
* Patients =\< 17 years of age must have a Lansky performance score of \>= 50
* Pediatric patients (age 5-17 years): A serum creatinine based on age/gender as follows (within 28 days prior to enrollment):
* 2 to \< 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female)
* 6 to \< 10 years (age): 1 mg/dL (male), 1 mg/dL (female)
* 10 to \< 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female)
* 13 to \< 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female)
* \>= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine creatinine clearance \>= 50 mL/min/1.73 m\^2 (within 28 days prior to enrollment) OR a glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2 (within 28 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* For adult patients (age 18 years or older) (within 28 days prior to enrollment): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
* Total bilirubin =\< 2 x upper limit of normal (ULN) (within 28 days prior to enrollment)
* Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
* Aspartate aminotransferase (AST) =\< 3 x ULN (within 28 days prior to enrollment)
* Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
* Alanine aminotransferase (ALT) =\< 3 x ULN (within 28 days prior to enrollment)
* Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
* Shortening fraction of \>= 27% by echocardiogram (ECHO), multigated acquisition scan (MUGA), or functional cardiac imaging scan (within 28 days prior to enrollment) or ejection fraction of \>= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging scan (within 28 days prior to enrollment)
* Diffusion capacity of the lung for carbon monoxide (DLCO) \>= 50% of predicted value as corrected for hemoglobin by pulmonary function test (PFT) (within 28 days prior to enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of \> 92% on room air
* Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion Criteria:
* Patients with nodular lymphocyte predominant Hodgkin lymphoma
* Patients with a history of active interstitial pneumonitis or interstitial lung disease
* Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly controlled or requiring active medications, such as primary immunodeficiency syndromes or organ transplant recipients
* Patients with any known uncontrolled intercurrent illness that would jeopardize the patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of pills
* Patients with a condition requiring systemic treatment with either corticosteroids (defined as equivalent to \> 10 mg daily predniSONE for patients \>= 18 years or \> 0.5 mg/kg \[up to 10 mg/day\] for patients \< 18 years) or other immunosuppressive medications within 14 days prior to enrollment
* Note: Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment. Inhaled or topical steroids, and adrenal replacement doses (=\< 10 mg daily for patients \>= 18 years or =\< 0.5 mg/kg \[up to 10 mg/day\] predniSONE equivalents) are permitted in the absence of active autoimmune disease
* Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued by cycle 1, day 1
* Short term use of corticosteroids for premedication or treatment of an allergy or hypersensitivity is considered an acceptable use of corticosteroids.
* Patients with peripheral neuropathy \> grade 1 at the time of enrollment or patients with known Charcot-Marie-Tooth syndrome
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL
* Prior solid organ transplant
* Prior allogeneic stem cell transplantation
* Live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, bacillus Calmette Guerin \[BCG\], oral polio vaccine, and oral typhoid). Administration of messenger ribonucleic acid (mRNA) vaccines are permitted
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test within 28 days prior to enrollment is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last treatment
* Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method for the duration of their study drug therapy. Following therapy, patients will be advised to use contraception as per institutional practice or as listed below for investigational agents, whichever is longer
* Men and women of childbearing potential must continue contraception for a period of 6 months after last dose of brentuximab vedotin
* Women of child-bearing potential (WOCBP) must continue contraception for a period of at least 5 months after the last dose of nivolumab
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection, BIOLOGICAL: Bleomycin Sulfate, DRUG: Brentuximab Vedotin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Dacarbazine, DRUG: Doxorubicin Hydrochloride, DRUG: Etoposide, DRUG: Etoposide Phosphate, OTHER: Fludeoxyglucose F-18, RADIATION: Involved-site Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography, DRUG: Prednisolone, DRUG: Prednisone, DRUG: Procarbazine Hydrochloride, OTHER: Questionnaire Administration, DRUG: Vinblastine Sulfate, DRUG: Vincristine Sulfate
Lugano Classification Limited Stage Hodgkin Lymphoma AJCC v8, Lymphoma
Children’s Health
ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC (PRESERVE-006)
In this Phase 2 study, mCRPC patients with PSMA positive scans who progressed on prior ARTA and up to 2 lines of taxanes, and are naïve to lutetium Lu 177 vipivotide tetraxetan, will be enrolled. The study is open-label, randomized with active control, multi-center study.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
MALE
18 Years and over
PHASE1
NCT05682443
STU-2023-0905
Inclusion Criteria:
• Patients must be ≥ 18 years of age and have the ability to understand and sign an approved informed consent form (ICF).
• Patients must have an ECOG performance status of 0 or 1.
• Patients must have a life expectancy \> 6 months.
• Patients must have histological or cytological confirmation of prostate adenocarcinoma.
• Patients must have a positive PSMA in an FDA-approved PSMA PET scan. A positive PSMA is defined as at least one tumor lesion with PSMA uptake greater than normal liver.
• Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
• Patients must have received at least one second generation AR-targeting agents (such as apalutamide, darolutamide, enzalutamide and/or abiraterone).
• Patients should have prior treatment of up to two taxane regimens, or are unfit for, or refuse taxane chemotherapy. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. Note: Taxane chemotherapy administered in the Castration Sensitive Prostate Cancer (CSPC) or Castration Resistant Prostate Cancer (CRPC) setting is allowed.
• Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
• Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 1.0 ng/mL.
• RECIST v1.1 soft-tissue progression
• Progression of bone disease: 2 or more new metastatic bone lesions by bone scan per PCWG3 criteria.
• Patients must have ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained ≤ 42 days prior to beginning study therapy.
• Patients must have adequate organ function.
• Patients with or without concomitant bisphosphonate or denosumab regimen for ≥ 30 days prior to randomization are eligible.
• For patients who have partners of childbearing potential: Partner and/or patient must use adequate methods of birth control with barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration.
Exclusion Criteria:
• Patients who have not recovered to NCI CTCAE grade ≤ 1 from an adverse event (AE) due to prior cancer therapeutics except neuropathy or endocrinopathy with Gr 2 or less.
• Any systemic anti-cancer therapy within 5 half-lives or 14 days, whichever is shorter (small molecule drugs) or within 28 days for antibody based therapy, prior to starting study treatment.
• Known hypersensitivity to the components of the study therapy or its analogs.
• Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
• Transfusion within 14 days of first day of study treatment
• PSMA-negative lesions are defined as lesions with PSMA uptake equal to or lower than that of liver parenchyma. Patients with PSMA-negative lesions in any lymph node with a short axis of ≥ 2.5 cm, in any metastatic solid-organ lesions with a short axis of ≥ 1.0 cm, or in any metastatic bone lesion with a soft-tissue component of ≥ 1.0 cm in the short axis are ineligible.
• Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to randomization. Previous PSMA-targeted radioligand therapy is not allowed.
• Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast).
• A superscan as seen in the baseline bone scan.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, myocardial infarction within 6 months, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, or unstable arrhythmia within 3 months, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
• Active concurrent malignancy (with the exception of non-melanomatous skin cancer). Patients with carcinoma in situ of any origin and patients with prior malignancies who are in remission and/or whose likelihood of recurrence is very low per investigator's judgment are eligible for this study.
• Receiving systemic steroid therapy with \> 10 mg/day prednisone or equivalent within 7 days prior to the first dose of study treatment or receiving any other form of immunosuppressive medication.
DRUG: ONC-392, DRUG: lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.
Metastatic Castration-resistant Prostate Cancer, Prostate
UT Southwestern
A Study to Test a Medicine (Fitusiran) Injected Under the Skin for Preventing Bleeding Episodes in Male Adolescent or Adult Participants With Severe Hemophilia (ATLAS-NEO)
This is a multicenter, multinational, open-label, one-way cross-over, Phase 3, single-arm study for treatment of hemophilia. The purpose of this study is to measure the frequency of treated bleeding episodes with fitusiran in male adult and adolescent (≥12 years old) participants with hemophilia A or B, with or without inhibitory antibodies to factor VIII or IX who have switched from their prior standard of care treatment. The total study duration will be up to approximately 50 months (200 weeks, 1 study month is equivalent to 4 weeks) and will include: - A screening period up to approximately 60 days, - A standard of care (SOC) period of approximately 6 study months (24 weeks), - A fitusiran treatment period of approximately 36 study months (144 weeks), - An antithrombin (AT) follow-up period of approximately 6 study months (24 weeks) but may be shorter or longer depending on individual participants AT recovery. The frequency for telephone visits will be approximately every 2 weeks. For site visits the frequency will be approximately every 8 weeks during the SOC period and approximately every 4 weeks during the fitusiran treatment period. If applicable and if allowed by local regulation, home and/or remote visits may be conducted during the study
Call 214-648-5005
studyfinder@utsouthwestern.edu, susan.corley@childrens.com
Jessica Garcia
Male
12 Years and over
Phase 3
NCT05662319
STU-2023-0024
Inclusion Criteria:
• Diagnosis of severe congenital hemophilia A or B (FVIII <1% or FIX level ≤2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
• For participants currently not on prophylaxis (CFC or BPA on-demand): A minimum of 4 bleeding episodes requiring BPA (inhibitor participants) or CFC (non-inhibitor participants) treatment within the last 6 months prior to screening.
• Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of participants under the age of legal consent, per local and national requirements
Exclusion Criteria:
• Known co-existing bleeding disorders other than congenital hemophilia A or B
• History of arterial or venous thromboembolism, not associated with an indwelling venous access
• History of intolerance to SC injection(s).
• Current participation in immune tolerance induction therapy (ITI)
• Prior gene therapy
• Current or prior participation in a fitusiran trial
• Current or prior participation in a gene therapy trial
• Received an investigational drug or device within 30 days prior to the screening visit or within 5 half-lives of the investigational drug (or device) prior to the screening visit, whichever is longer
• Presence of clinically significant liver disease AT activity <60% at Screening
• Co-existing thrombophilic disorder
• Hepatitis C virus antibody positive, except participants who have negative Hepatitis C viral load and no evidence of cirrhosis
• Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
• Presence of acute or chronic hepatitis B infection
• Known to be HIV positive with CD4 count <200 cells/μL.
• Reduced renal function The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Drug: Fitusiran, Drug: Clotting factor concentrates (CFC) or bypassing agents (BPA), Drug: Antithrombin concentrate (ATIIIC)
Hemophilia
Children’s Health
MFOLFIRINOX Versus MFOLFOX with or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
This phase III trial compares the effect of modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) for the treatment of advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The usual approach for patients is treatment with FOLFOX chemotherapy. Chemotherapy drugs 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. Fluorouracil stops cells from making DNA and it may kill tumor cells. Leucovorin is used with fluorouracil to enhance the effects of the drug. Oxaliplatin works by killing, stopping, or slowing the growth of tumor cells. Some patients also receive an immunotherapy drug, nivolumab, in addition to FOLFOX chemotherapy. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill tumor cells. Adding irinotecan to the FOLFOX regimen could shrink the cancer and extend the life of patients with advanced gastroesophageal cancers.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Timothy Brown
ALL
18 Years to old
PHASE3
NCT05677490
STU-2024-0324
Inclusion Criteria:
* Histologic documentation: HER2 negative adenocarcinoma as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines (Bartley et al., Journal of Clinical Oncology \[JCO\] 2017) with known PD-L1 CPS (Any CPS is allowed, but should be known prior to registration)
* Stage: unresectable or metastatic
* Tumor site: esophagus, gastroesophageal junction, or stomach
* Measurable disease or non-measurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No prior treatment for unresectable or metastatic disease
* Prior neoadjuvant or adjuvant cytotoxic chemotherapy or adjuvant immunotherapy is allowed as long as it was completed at least 1 year prior to registration
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 30 mL/min
* Total bilirubin =\< 1.5 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (in patients with liver metastasis: =\< 5 x ULN if clearly attributable to liver metastases)
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients positive for human immunodeficiency virus (HIV) are eligible only if they meet all of the following:
* On effective anti-retroviral therapy
* Undetectable HIV viral load by standard clinical assay =\< 6 months of registration
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patients who will receive nivolumab in addition to chemotherapy must not have any contraindications to immune checkpoint inhibitors
* Patients must not have active autoimmune disease that has required systemic treatment within 6 months prior to registration. Patients are permitted to receive immunotherapy if they have vitiligo, type I diabetes, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
* Patients must not have a condition requiring systemic treatment with either corticosteroids (\>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses (=\< 10mg/day prednisone equivalent) are permitted
* Patients must not have a history of noninfectious pneumonitis requiring steroids
* Patients with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents are ineligible
* This study includes the use of the mandatory patient completed measure, PRO-CTCAE. For this study the PRO-CTCAE is available in English, Spanish, Korean, Chinese (Simplified), and Russian, hence patients must be able to speak, understand and read in these languages. Ad-hoc translation of patient-reported measures is not permitted
Exclusion Criteria:
* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
\* Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =\< 7 days prior to registration is required
* No known Gilbert's syndrome or known homozygosity for UGAT1A1\*28 polymorphism
* No baseline grade \>= 2 peripheral neuropathy, neurosensory toxicity, or neuromotor toxicity per CTCAE version (v) 5.0 regardless of causality
* No medical condition such as uncontrolled infection or uncontrolled diabetes mellitus which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* No untreated, symptomatic brain metastasis. Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose for more than four weeks
* No allogeneic tissue/organ transplant DRUG: Fluorouracil, DRUG: Leucovorin Calcium, DRUG: Oxaliplatin, DRUG: Irinotecan, BIOLOGICAL: Nivolumab, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Computed Tomography, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Advanced Esophageal Adenocarcinoma, Advanced Gastric Adenocarcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Esophageal Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Unresectable Esophageal Adenocarcinoma, Unresectable Gastric Adenocarcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma, Esophagus, Stomach
UT Southwestern; Parkland Health & Hospital System
A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma
A Phase I study to evaluate the safety of a novel, orally available, selective, and potent small molecule inhibitor of the histone lysine methyl transferase MMSET (also known as NSD2/WHSC1) to prevent the dimethylation of H3K36 in adult patients with relapsed or refractory multiple myeloma (RRMM).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aimaz Afrough
All
18 Years and over
Phase 1
NCT05651932
STU-2023-0538
Key
• ≥ 18 years of age
• ECOG score ≤ 2
• Relapsed or refractory multiple myeloma (as per IMWG)
• ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
• Patients must have exhausted available therapeutic options that are expected to provide a meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance, or refusal of the therapy
• t(4;14) confirmed by standard of care FISH testing, or GOF mutation in MMSET confirmed by local sequencing test (Part B dose expansion cohorts only)
• Measurable disease, including at least 1 of the following criteria:
• Serum M protein ≥ 0.50 g/dL (by SPEP)
• Serum IgA ≥ 0.50 g/dL (IgA myeloma patients)
• Urine M protein ≥ 200 mg/24 h (by UPEP)
• sFLC involved light chain ≥ 10 mg/dL (100 mg/L) (patients with abnormal sFLC ratio)
• ≥ 1 extramedullary lesion ≥ 1 cm in size and able to be followed by imaging assessments (Part A dose escalation cohorts only)
• Bone marrow plasma cells ≥ 10% (Part A dose escalation cohorts only) Key
• Treatment with the following therapies in the specified time period prior to first dose:
• Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks
• Cellular therapies ≤ 8 weeks
• Autologous transplant < 100 days
• Allogenic transplant ≤ 6 months, or > 6 months with active GVHD
• Major surgery ≤ 4 weeks
• History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone lesion or bone lesions as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm or light chain amyloidosis
• Active CNS disease
• Inadequate bone marrow function
• Inadequate renal, hepatic, pulmonary, and cardiac function
• Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Permitted prophylactic medications, antimicrobials or antiretroviral therapies defined in protocol.
• Use of acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to first dose
• Active malignancy not related to myeloma requiring therapy within < 3 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.
Inclusion Criteria:
• ≥ 18 years of age
• ECOG score ≤ 2
• Relapsed or refractory multiple myeloma (as per IMWG)
• ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
• Patients must have exhausted available therapeutic options that are expected to provide a meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance, or refusal of the therapy
• t(4;14) confirmed by standard of care FISH testing, or GOF mutation in MMSET confirmed by local sequencing test (Part B dose expansion cohorts only)
• Measurable disease, including at least 1 of the following criteria:
• Serum M protein ≥ 0.50 g/dL (by SPEP)
• Serum IgA ≥ 0.50 g/dL (IgA myeloma patients)
• Urine M protein ≥ 200 mg/24 h (by UPEP)
• sFLC involved light chain ≥ 10 mg/dL (100 mg/L) (patients with abnormal sFLC ratio)
• ≥ 1 extramedullary lesion ≥ 1 cm in size and able to be followed by imaging assessments (Part A dose escalation cohorts only)
• Bone marrow plasma cells ≥ 10% (Part A dose escalation cohorts only) Key
Exclusion Criteria:
• Treatment with the following therapies in the specified time period prior to first dose:
• Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks
• Cellular therapies ≤ 8 weeks
• Autologous transplant < 100 days
• Allogenic transplant ≤ 6 months, or > 6 months with active GVHD
• Major surgery ≤ 4 weeks
• History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone lesion or bone lesions as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm or light chain amyloidosis
• Active CNS disease
• Inadequate bone marrow function
• Inadequate renal, hepatic, pulmonary, and cardiac function
• Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Permitted prophylactic medications, antimicrobials or antiretroviral therapies defined in protocol.
• Use of acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to first dose
• Active malignancy not related to myeloma requiring therapy within < 3 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.
Drug: KTX-1001
Multiple Myeloma, Myeloma, Myeloma Multiple, Myeloid and Monocytic Leukemia
NSD2, MMSET, WHSC1, T4,14, T(4,14), translocation, myeloma, RRMM
UT Southwestern
A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Adult Participants With Aggressive B-cell Non-Hodgkin Lymphomas (ATHENA-1)
The study is researching an experimental drug called REGN5837 in combination with another experimental drug, odronextamab (called "study drugs"). The aim of the study is to see how safe and tolerable the study drugs are, and to define the recommended dose for phase 2. The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drugs (that could make the drugs less effective or could lead to side effects) * To find out how well the study drugs work against relapsed or refractory aggressive B-cell non-Hodgkin lymphomas (B-NHLs)
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
ALL
18 Years and over
PHASE1
NCT05685173
STU-2023-0841
Key
• Have documented CD20+ aggressive B-NHL, with disease that has progressed after at least 2 lines of systemic therapy containing an anti-CD20 antibody and an alkylating agent, as described in the protocol.
• Measurable disease on cross sectional imaging as defined in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate bone marrow, renal and hepatic function as defined in the protocol
• Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed
• During dose expansion phase of the study, participant should be willing to undergo mandatory tumor biopsies, if in the opinion of the investigator, the participant has an accessible lesion that can be biopsied without significant risk to the participant. Key
• Prior treatments with allogeneic stem cell transplantation or solid organ transplantation, treatment with anti-CD20 x anti- CD3 bispecific antibody, such as odronextamab
• Diagnosis of mantle cell lymphoma (MCL)
• Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS lymphoma, as described in the protocol
• Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 14 days prior to first administration of study drug, whichever is shorter, as described in the protocol
• Standard radiotherapy within 14 days of first administration of study drug, as described in the protocol
• Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or corticosteroid equivalent within 72 hours of start of odronextamab
• Co-morbid conditions, as described in the protocol
• Infections, as described in the protocol
• Allergy/hypersensitivity: Known hypersensitivity to both allopurinol and rasburicase NOTE: Other protocol defined inclusion / exclusion criteria apply
Inclusion Criteria:
• Have documented CD20+ aggressive B-NHL, with disease that has progressed after at least 2 lines of systemic therapy containing an anti-CD20 antibody and an alkylating agent, as described in the protocol.
• Measurable disease on cross sectional imaging as defined in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate bone marrow, renal and hepatic function as defined in the protocol
• Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed
• During dose expansion phase of the study, participant should be willing to undergo mandatory tumor biopsies, if in the opinion of the investigator, the participant has an accessible lesion that can be biopsied without significant risk to the participant. Key
Exclusion Criteria:
• Prior treatments with allogeneic stem cell transplantation or solid organ transplantation, treatment with anti-CD20 x anti- CD3 bispecific antibody, such as odronextamab
• Diagnosis of mantle cell lymphoma (MCL)
• Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS lymphoma, as described in the protocol
• Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 14 days prior to first administration of study drug, whichever is shorter, as described in the protocol
• Standard radiotherapy within 14 days of first administration of study drug, as described in the protocol
• Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or corticosteroid equivalent within 72 hours of start of odronextamab
• Co-morbid conditions, as described in the protocol
• Infections, as described in the protocol
• Allergy/hypersensitivity: Known hypersensitivity to both allopurinol and rasburicase NOTE: Other protocol defined inclusion / exclusion criteria apply
DRUG: Odronextamab, DRUG: REGN5837
B-cell Non-Hodgkins Lymphoma (B-NHL), Non-Hodgkins Lymphoma
Aggressive B-Cell Non-Hodgkin Lymphomas, Relapsed or Refractory
UT Southwestern
Hyperbaric Oxygen Therapy for Post-Concussion Syndrome
The purpose of this study is to decrease symptom burden, improve cognitive function, and improve quality of life outcomes in subjects with mild TBI and persisting post-concussion syndrome using Hyperbaric Oxygen Treatment compared to a sham intervention. Specific Aims: 1. Evaluate the efficacy of hyperbaric oxygen treatment to improve outcomes for adults with persisting post-concussion syndrome. Specifically, the investigators hypothesize that a prescribed course of hyperbaric oxygen treatments (HBOT) will improve outcomes and quality of life in adults with persisting symptoms >3 months after injury. 1. Decrease symptom burden as measured by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). 2. Improve cognitive function as measured by the National Institutes of Health (NIH) Toolbox Cognition Battery. 3. Improve quality of life as measured by the 36-Item Short Form Survey (SF-36). 2. Assess the safety and tolerability of hyperbaric oxygen treatments and compliance with treatment in adults with persisting post-concussion syndrome.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Petra.Gonzalez@UTSouthwestern.edu
Shanti Pinto
All
18 Years to 65 Years old
N/A
NCT05643482
STU-2022-0697
Inclusion Criteria:
• Must have been evaluated within 3 weeks of injury and given a diagnosis of concussion by a medical professional
• Must be experiencing persistent symptoms 3-12 months after injury as defined as having at least symptoms that are moderate to severe (score 3-4) OR at least a total score of 10 with at least 1 symptom rated moderate to severe (3-4) on the Rivermead Post-Concussion Questionnaire (RPQ).
Exclusion Criteria:
Clinically significant cardiac, neurological, psychological/psychiatric, or respiratory
impairment in the opinion of the investigators, including but not limited to:
• Pulmonary:
• COPD with CO2 retention; previous/current imaging showing hyperinflation/air trapping/bullous disease/blebs
• Current pneumothorax or previous spontaneous pneumothorax
• Cardiac:
• Uncontrolled HTN (systolic >180 or diastolic >100)
• Known Ejection fraction < 35%
• Pacemaker / ICD in place (not approved for chamber use)
• Hematological/Oncological:
• Current chemotherapeutic drug use, and past history of bleomycin use.
• Hereditary Spherocytosis
• Sickle cell anemia
• Neurological and Psychological:
• Implanted nerve stimulators
• Uncontrolled seizure disorder
• Drug or alcohol abuse/dependence
• Current treatment for alcohol cessation with disulfiram
• Claustrophobia
• Head and Neck:
• Inability to equilibrate the pressure of middle ears and sinuses
• Current or previous retinal detachment
• Retinal or vitreous surgery within the past 3 months
• Miscellaneous:
• Current fever or active infection
• Implanted devices not on the approved list for use with HBOT
• Women who are pregnant. Women with childbearing potential are required to use effective birth control if not surgically sterile or postmenopausal for >2 years.
• Undergoing vestibular or other therapy during the intervention
• Planning a change in medication during the intervention
• Relative exclusion criteria: Diagnosis of the conditions listed below will require approval of the hyperbaric medicine physician for enrollment into the study.
• Asthma
• Optic neuritis
• Otosclerosis surgery
• Thoracic surgery
• Chronic sinusitis
• Medications: Individuals with recent (within the past six months) or concurrent use of these medications must be approved by the hyperbaric medicine physician.
• Antabuse - Predisposes to oxygen toxicity
• Antiseizure medications - Potential participants must have levels of their seizure medications checked within a week of their initial screening visit because low levels can predispose to oxygen toxicity. Laboratory testing must be completed by their outside treating physicians to provide to the research staff for review; the study will not obtain labs for monitoring medication levels as part of the inclusion/exclusion criteria
• Meclizine - Predisposes to oxygen toxicity
• Bleomycin - May cause pulmonary fibrosis that can lead to air embolism or pneumothorax in the patient receiving hyperbaric oxygen treatment.
• Certain ointments/creams that cannot be removed - These may be allowed if covered with cotton dressings.
• Narcotics - Can lead to cessation of the hypoxic respiratory drive.
• Nitroprusside - HBOT vasoconstrictive effect interacts with nitroprusside's vasodilator effect, making intensive monitoring mandatory.
• Penicillin - Predisposes to oxygen toxicity
• Promethazine (Phenergan) - Predisposes to oxygen toxicity.
• Corticosteroids - Decreases the threshold for oxygen toxicity.
• Sulfamylon - Promotes CO2 buildup causing peripheral vasodilatation. When coupled with vasoconstriction, results are worse than with using either agent alone. Use silver sulfadiazine instead for wound care.
Device: Hyperbaric Oxygen Treatment, Other: Placebo gas
Post-Concussion Syndrome, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System
Study to Evaluate ARINA-1 in the Prevention of Bronchiolitis Obliterans Progression in Participants With Bilateral Lung Transplant
The goal of this clinical trial is to compare ARINA-1 plus Standard of Care vs Standard of Care alone. The main question it aims to answer are: * Evaluate the effectiveness of ARINA-1 in preventing bronchiolitis obliterans syndrome (BOS) progression in participants with a bilateral lung transplant * To evaluate the effectiveness of ARINA-1 on improving quality of life decline and preventing or delaying the use of augmented immunosuppression in participants with pre-BOS relative to SOC. Participants will have clinic visits at screening, randomization (day 1) and weeks 4, 12, 18, and 24. After week 24, participants will have clinic visits at weeks 32, 40, and 48. Participants will also have a telehealth visit on day 2 and phone calls to assess adverse events (AEs), serious adverse events (SAEs), and review patient education will occur during weeks 5, 8, 36, and 44.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ramatoulaye.Diallo@UTSouthwestern.edu
Vaidehi Kaza
ALL
18 Years to 75 Years old
PHASE3
NCT05654922
STU-2023-0149
Inclusion Criteria:
• Bilateral lung transplant \>12 months from the time of Visit 1 / Randomization
• Age 18-75 years old at the time of consent
• Routinely followed at enrolling site
• Willing and able to comply with visit schedule and at-home requirements
• 10-24% decrease in FEV1 from the post-transplant baseline within the last 12 months.
• Capable of giving informed consent
• On a stable maintenance regimen of azithromycin for \>4 weeks prior to the Screening Visit
• On a stable 3-agent immunosuppression regimen that includes a steroid, a calcineurin inhibitor (CNI), and cell cycle inhibitor (e.g., mycophenolate, azathioprine) \>4 weeks prior to Screening
• If a woman of childbearing potential (WOCBP), must agree to use a reliable method of birth control for the entire duration of the study.
Exclusion Criteria:
• Positive urine pregnancy test at screening and baseline visit
• Diagnosis of active congestive heart failure or symptomatic coronary artery disease \> grade 3 based on the New York Heart Association Functional Classification (NYHA) criteria
• Restrictive allograft syndrome (RAS) defined by radiographic interstitial or alveolar opacities on chest X-ray or CT scan that are consistent with RAS
• Have advanced BOS, defined by \>24% decrease in FEV1 in post-transplant baseline
• A diagnosis of probable antibody-mediated rejection (AMR) \<12 months prior to the baseline visit
• Donor-specific antibodies (DSA) identified \<6 months prior to the baseline visit. \*The presence of DSA \>6 months from the baseline visit is acceptable for enrollment into the study.
• Unresolved diffuse alveolar damage
• Receiving mechanical ventilation
• Chronic kidney disease stage IV or higher, including on dialysis
• Initiating a new maintenance therapy or changing immunosuppression maintenance therapy (e.g., changing tacrolimus to cyclosporine) \<14 days prior to the baseline visit.
• Currently using an mTOR inhibitor or azathioprine
• Initiating or changing antibiotic (including azithromycin), antiviral, or antifungal therapy \<14 days prior to the baseline visit.
• Use of alemtuzumab \<6 months prior to the baseline visit
• Use of anti-thymocyte therapies (e.g., anti-thymocyte globulin) or photopheresis \<90 days prior to the Screening Visit. Prior use of Trikafta (elexacaftor, ivacaftor, and tezacaftor is allowed as long as the participant has been on stable dose for \>90 days prior to the Screening Visit.
• Initiating a multivitamin or other supplement (inhaled, oral, or IV) containing vitamin C, glutathione, or N-acetylcysteine \<90 days prior to the baseline visit
• Significant unstable comorbidities, in the opinion of the site investigator
• Allery or previous adverse reaction to azithromycin
• A diagnosis of dynamic collapse / tracheobrochomalacia \<90 days of the baseline visit.
• Subjects currently participating in, or who have participated in an interventional (drug or device) clinical study \<30 days of the baseline visit.
• Have been diagnosed with ARAD within 6 weeks of the Screening Visit.
• Have used belatacept \<6 months prior to Clinic Visit 1
• Have had bronchial stents or cryotherapy within 12 months of the Screening Visit
DRUG: ARINA-1, OTHER: Standard of care only
Pre-Bronchiolitis Obliterans Syndrome
UT Southwestern
Impact of Sentinel Lymph Node Mapping on Patient Reported Lower Extremity Limb Dysfunction in Stage I Endometrial Cancer
This phase III trial compares the effect of sentinel lymph node mapping to standard lymph node dissection in reducing the risk of swelling in the legs (lymphedema) in patients undergoing a hysterectomy for stage I endometrial cancer. Standard lymph node dissection removes lymph nodes around the uterus during a hysterectomy to look for spread of cancer from the uterus to nearby lymph nodes. Sentinel lymph node mapping uses a special dye and camera to look for cancer that may have spread to nearby lymph nodes. Comparing the results of the procedures may help doctors predict the risk of long-term swelling in the legs.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jayanthi Lea
FEMALE
18 Years and over
PHASE3
NCT05646316
STU-2023-0908
Inclusion Criteria:
* Histologically proven diagnosis of endometrial cancer based on endometrial sampling with a plan to undergo laparoscopic or robotic hysterectomy and lymphatic assessment as part of primary management. Biopsy must be performed within 90 days prior to registration
* Clinical stage I endometrial cancer based on the following diagnostic workup:
* History/physical examination within 30 days prior to registration is reassuring for the absence of metastatic disease
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
* Patients must speak English or Spanish
Exclusion Criteria:
* Patients whom the surgeon believes is not a candidate for pelvic lymphadenectomy due to medical comorbidities or other technical challenges (i.e. morbid obesity or prior surgery)
* History of chemotherapy or immunotherapy for the treatment of endometrial cancer. Progestin-containing therapies such as megestrol, medroxyprogesterone, or levonorgestrel-containing intrauterine device (IUD) are acceptable
* History of radiation to the pelvis, groin or lower extremities, or surgery to the pelvic lymph nodes or inguinal lymph nodes
* Patients who are going to undergo another elective surgery during the same operative event as their hysterectomy (i.e., sacrocolpopexy, cholecystectomy)
* Patients with severe, active co-morbidity defined as follows:
* History of patient or provider identified lower extremity lymphedema
* History of patient or provider identified chronic lower extremity swelling
* History of lower extremity or pelvic deep venous thromboembolism within 90 days of registration
* History of lower extremity cellulitis within 90 days of registration
* For the bioimpedance sub study only: patients with implantable metal devices (i.e. defibrillator, metal joint replacements, etc.) will not be eligible to participate in the bioimpedance sub study but will be eligible to participate in the overall study PROCEDURE: Biospecimen Collection, PROCEDURE: Diagnostic Imaging, PROCEDURE: Excisional Biopsy, DRUG: Indocyanine Green Solution, PROCEDURE: Minimally Invasive Surgery, PROCEDURE: Pelvic Lymphadenectomy, OTHER: Questionnaire Administration, PROCEDURE: Sentinel Lymph Node Mapping
Stage I Uterine Corpus Cancer AJCC v8, Corpus Uteri
UT Southwestern; Parkland Health & Hospital System
Canakinumab for the Prevention of Progression to Cancer in Patients With Clonal Cytopenias of Unknown Significance, IMPACT Study
This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE2
NCT05641831
STU-2024-0699
Inclusion Criteria:
* Patients with age \>= 18 with high-risk CCUS
* Must meet ALL the following criteria:
* Unexplained, clinically meaningful cytopenias (greater than 4 months) in one or more of the following lineages: erythroid cells, neutrophils, platelets. Clinically meaningful cytopenia is institution specific and threshold may vary on age, sex, and race. Decision-making should depend upon lab values specific to the institution and supersede public works. Based upon published work, significant cytopenias are defined as the following:
* Erythroid Cells:
* Hemoglobin \< 11 g/dL
* White Blood Cells:
* Absolute Neutrophil Count \< 1800/microL and \> 500/microL
* Platelets:
* Platelet Count \< 150,000/microL and \> 50,000/microL
* MDS criteria not fulfilled
* No other evidence of hematological malignancy
* No or only mild (\< 10%) bone marrow dysplasia
* Blast cells \< 5% detected via morphologic examination of blood and/or bone marrow smears which can also be supported by flow cytometry and/or immunohistochemical studies
* Any of the following:
* Isolated somatic spliceosome mutation at any VAF (SRSF2, SF3B1, U2AF1, or ZRSR2)
* Isolated TP53 mutation greater than 5% VAF
* At least 1 mutation in TET2, DMNT3A, or ASXL1 at any VAF coupled with at least 1 other known myeloid pathogenic somatic mutation or known pathogenic germline mutation that predisposes to myeloid malignancy as determined by next generation sequencing and bone marrow biopsy
* A TET2, DMNT3A, or ASXL1 greater than 10% VAF coupled with another TET2, DMNT3A, or ASXL1 greater than 10% VAF
* The presence of two or more known myeloid pathogenic somatic or germline mutations (other than TET2, ASXL1, DMNT3A, TP53, or spliceosome mutations) greater than 10% VAF
* Ability to understand and willingness to sign the written informed consent document
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Patients with a history of hypertension or active hypertension are strongly encouraged to optimize blood pressure control
* Creatinine clearance greater than 45 ml/min using Cockcroft-Gault
* Total bilirubin =\< 1.5 x ULN
* Aspartate transaminase (AST) \< 3 x ULN
* Alanine transaminase (ALT) \< 3 x ULN
Exclusion Criteria:
* Concurrent malignancy requiring active systemic therapy
* Diagnosis of MDS or any other myeloid malignancy in the patient's lifetime
* History of Hypersensitivity to canakinumab or drug of a similar class
* Active infection requiring prompt evaluation and treatment or history of recurrent infections
* Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (via positive or indeterminate central laboratory \[lab\] results)
* Subjects with active tuberculosis. In subjects without active tuberculosis, if the results of the evaluation require treatment per local guidelines, then the treatment should be initiated before randomization (unless otherwise required by Health Authorities or Institutional Review Board (IRB) in which case curative treatment must be completed prior to screening)
* Subjects with suspected or proven immunocompromised state or infections. If the results of this screening per local treatment guidelines or clinical practice require treatment for said infection then the patient is not eligible. Suspected or proven immunocompromised states or infections include:
* Those with any other medical condition such as active infection, treated or untreated, which in the opinion of the investigator places the subject at an unacceptable risk for participation in immunomodulatory therapy
* Known history of testing positive for human immunodeficiency virus (HIV) infections. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
* Allogeneic bone marrow or solid organ transplant (history of any or within a certain period of time?)
* Those requiring systemic or local treatment with any immune modulating agent in doses with systemic effects e.g.:
* Prednisone \> 20 mg (or equivalent) oral or intravenous daily for \> 14 days
* Prednisone \> 5 mg and =\< 20 mg (or equivalent) daily for \> 30 days
* Equivalent dose of methotrexate \> 15 mg weekly
* Note: Azathioprine is allowed. Daily glucocorticoid-replacement for conditions such as adrenal or pituitary insufficiency is allowed. Topical, inhaled or local steroid use in doses that are not considered to cause systemic effects are permitted. Steroids for pre-medication related to chemotherapy as per local standard of care are permitted.
* Live or attenuated vaccination within 3 months prior to first dose of study drug (e.g. Measles/Mumps/Rubella \[MMR\], Yellow Fever, Rotavirus, Smallpox, etc.) and after initiation of canakinumab treatment
* Use of erythropoietin stimulating agents (ESA) or growth factors within four weeks prior to the start of the study
* Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment and for up to 130 days after last dose of study drug. Basic contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
* Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
* Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Prior to entry into this study, cisplatin-based chemotherapy, which may be toxic to the fetus, may be given. The time between the end of cisplatin-based chemotherapy and the start canakinumab/placebo treatment is variable, resulting in a variable need for continuation of highly effective contraception. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks prior to first dose of study drug. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF). PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Canakinumab, PROCEDURE: Chest Radiography, PROCEDURE: Echocardiography, DRUG: Placebo Administration, OTHER: Quality-of-Life Assessment
Clonal Cytopenia of Undetermined Significance, Myeloid and Monocytic Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
UT Southwestern
A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Heart Failure and Inflammation (HERMES)
This study will be done to see if ziltivekimab can be used to treat people living with heart failure and inflammation. Participants will either get ziltivekimab or placebo. Participants will get study medicine for once-monthly injections either in a pre-filled syringe to inject the study medicine into a skinfold or a pen-injector to inject the study medicine into flat skin. The study is expected to last for up to 4 years. Participants will have up to 20 clinic visits. Participants will have to use a study app on their phone to record and share information about all their injections of study medicine and to fill in questionnaires.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Daniel.Ayodele@UTSouthwestern.edu
Alvin Chandra
ALL
18 Years and over
PHASE3
NCT05636176
STU-2023-0359
Inclusion Criteria:
* Serum high-sensitivity C-reactive protein (hs-CRP) greater than equal to 2 milligrams per liter (mg/L) at screening (visit 1) Disease specific - cardiovascular
* At least one of the following:
• N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than equal to 300 picograms per milliliter (pg/mL) at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NTproBNP must be greater than equal to 600 pg/mL. Note that the screening electrocardiogram (ECG) must be obtained the same day as sampling for NT-proBNP.
• Hospitalisation or urgent/unplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the last 9 months prior to screening (visit 1) in combination with NT-proBNP greater than equal to 200 pg/mL at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NT-proBNP must be greater than equal to 600 pg/mL. * Diagnosis of heart failure (New York Heart Association \[classification\] \[NYHA\] Class II-IV). * Left ventricular ejection fraction (LVEF) greater than 40 percentage (%) documented by echocardiography within 12 months prior to or at screening (visit 1). The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (e.g., myocardial infarction \[MI\] or heart failure \[HF\] hospitalisation). * Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening (visit 1) showing at least one of the following: * Left atrial (LA) volume index greater than 34 milliliter per meter square (mL/m\^2). * LA diameter greater than equal to 3.8 centimeter (cm). * LA length greater than equal to 5.0 cm. * LA area greater than equal to 20 cm square. * LA volume greater than equal to 55 milliters (mL). * Intraventricular septal thickness greater than equal to 1.1 cm. * Posterior wall thickness greater than equal to 1.1 cm. * Left ventricular (LV) mass index greater than equal to 115 grams per meter square (g⁄m\^2 ) in men or greater than equal to 95 g⁄m\^2 in women. * E/e' (mean septal and lateral) greater than equal to 10. * e' (mean septal and lateral) less than 9 centimeter per second (cm/s). * No heart failure hospitalisations or urgent heart failure visits between screening (visit 1) and randomisation (visit 2).
Exclusion Criteria:
Medical conditions - cardiovascular
* Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation, within 30 days prior to screening (visit 1).
* Systolic blood pressure greater than equal to 180 millimeters of mercury (mmHg) at screening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patient should be receiving greater than equal to 3 antihypertensive drugs. (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
* Heart rate above 110 or below 40 beats per minute as evaluated on the electrocardiogram (ECG) performed at screening (visit 1) (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
* Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1). (Note: Planned coronary angiogram is not exclusionary).
* Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period (visit 1).
* Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2).
* Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primary valve disease.
* Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
* Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism).
Medical conditions - infections/immunosuppression
• Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
DRUG: Ziltivekimab, DRUG: Placebo
Heart Failure
UT Southwestern
A Multi-Institution Study of TGFβ Imprinted, Ex Vivo Expanded Universal Donor NK Cell Infusions As Adoptive Immunotherapy in Combination with Gemcitabine and Docetaxel in Patients with Relapsed or Refractory Pediatric Bone and Soft Tissue (TINKS)
The purpose of this study is to determine if the addition of infusions of a type of immune cell called a "natural killer", or NK cell to the sarcoma chemotherapy regimen GEM/DOX (gemcitabine and docetaxel) can improve outcomes in people with childhood sarcomas that have relapsed or not responded to prior therapies. The goals of this study are: * To determine the safety and efficacy of the addition of adoptive transfer of universal donor, TGFβ imprinted (TGFβi), expanded NK cells to the pediatric sarcoma salvage chemotherapeutic regimen gemcitabine/docetaxel (GEM/DOX) for treatment of relapsed and refractory pediatric sarcomas To determine the 6-month progression free survival achieved with this treatment in patients within cohorts of relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcoma. * To identify toxicities related to treatment with GEM/DOX + TGFβi expanded NK cells Participants will receive study drugs that include chemotherapy and NK cells in cycles; each cycle is 21 days long and you can receive up to 8 cycles. * Gemcitabine (GEM): via IV on Days 1 and 8 * Docetaxel (DOX): via IV on Day 8 * Prophylactic dexamethasone: Day 7-9 to prevent fluid retention and hypersensitivity reaction * Peg-filgrastim (PEG-GCSF) or biosimilar: Day 9 to help your white blood cell recover and allow more chemotherapy to be given * TGFβi NK cells: via IV on Day 12
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
2 Years to 40 Years old
PHASE1
NCT05634369
STU-2023-0706
Inclusion Criteria:
• Patients must be between the ages \> 12 years and ≤ 40 years of age and have had a relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma.
• Patients must have measurable disease using RECIST 1.1 criteria
• Patients must have had at least one and no more than four total lines of systemic treatment for relapse sarcoma. Local control with surgical resection or radiation therapy of the primary tumor and any metastatic sites as clinically indicated as standard of care per the treating physician must be considered prior to enrollment.
• Prior Therapy: Therapy may not have been received more recently than the timeframes defined below: * Myelosuppressive chemotherapy: Patients must not have received myelosuppressive therapy within 14 days of protocol therapy * Radiation: At least 2 weeks must have elapsed from the start of protocol therapy since local palliative XRT (small port); 4 weeks must have elapsed for all other radiation therapy * Hematopoietic Cell Transplant (HCT): Patients must have at least 6 weeks elapsed after autologous and allogeneic hematopoietic cell transplant * Biologic (anti-neoplastic agent): At least 7 days or 5 half-lives of the drug, whichever is longer, must have elapsed from the start of protocol therapy since the completion of therapy with a biologic agent. * Monoclonal antibodies: At least 3 weeks must have elapsed from the start of protocol therapy since prior therapy that included a monoclonal antibody. * Prior use of Gemcitabine and/or Docetaxel: Patients who have received these agents for prior treatment may be included if previous treatments were given ≥ 6 months prior to enrollment on this study, and there were no allergic reactions, pulmonary edema or fibrosis, Grade 3 or higher neuropathy or other non-hematologic Grade 4 adverse events related to gemcitabine and/or docetaxel therapies. 4) Performance status: Karnofsky ≥ 60 for patients ≥16 years of age. Lansky score of ≥ 60 for patients \< 16 years of age (see Appendix A) 5) Organ Function Requirements: Patients must have normal organ and marrow function within 7 days of starting protocol therapy as defined below: * Absolute Neutrophil Count ≥1000/mcL * Platelet count ≥100,000/mcL independent of transfusion * Total bilirubin \< 1.5x upper limit of normal for age * AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal * Serum creatinine \< 1.5 x upper limit of normal based on age/gender (Table 3) OR creatinine clearance ≥70 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Shortening fraction ≥ 27% by ECHO OR ejection fraction of ≥ 50% by ECHO or gated radionuclide study * Echocardiogram done within 12 months of study entry will be acceptable. If patient has required anthracycline chemotherapy since last ECHO and enrollment on this study, echocardiogram should be repeated. * No evidence for dyspnea at rest, no chronic oxygen requirement, and room air pulse oximetry \>94% if there is a clinical indication for pulse oximetry 6) Neuropathy: Patients must have ≤ Grade 2 neuropathy at enrollment 7) Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsant, with the exception of diazepam given its potential deleterious effects on NK cell activity. 8) Contraception: The effects of expanded NK cells on the developing human fetus are unknown. For this reason and because the chemotherapeutic preparative agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of preparatory regimen administration. 9) All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent/assent document.
Exclusion Criteria:
• Patients who are receiving any other investigational agents.
• Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer
• Patients with a history of allergic reactions attributed to docetaxel, gemcitabine, or peg-filgrastim or biosimilar
• Patients who have received any prior cellular therapies, such as CAR-T cells or other expanded or manufactured cellular products.
• Patients with bone marrow only disease are not eligible for this study.
• Patients who, in the judgment of the treating physician, has tumors near critical structures for which transient swelling would cause substantial symptoms, such as tumor within the bowel mucosa
• Patients with CNS metastatic disease will not be eligible for this study.
• Concomitant Medications: * Due to their effect on NK cell function, systemic corticosteroids outside of the supportive dexamethasone given from day 7 through 9 should be used ONLY for life-threatening conditions (i.e., life-threatening allergic reactions and anaphylaxis such as bronchospasm, stridor) unresponsive to other measures. The use of dexamethasone as an anti-emetic is not permitted. Corticosteroid therapy can be used as a premedication for transfusion in patients known to have a history of transfusion reactions or for treatment of an unexpected transfusion reaction (hydrocortisone 2 mg/kg or less or an equivalent dose of an alternative corticosteroids). The use of steroids during protocol therapy other than the study- required prophylactic dexamethasone doses requires clear justification and documentation of use for a life-threatening condition. * The following are also prohibited while on study treatment * Strong CYP3A4 inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians' Desk Reference may also provide this information. * Diazepam * Chemotherapeutic agents other than the study drugs
• Uncontrolled intercurrent illness including, but not limited to: * ongoing or active infection * psychiatric illness/social situations that would limit compliance with study requirements
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies with Gemcitabine and Docetaxel
• HIV Infection: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study medications. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• 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.
BIOLOGICAL: GEM/DOX + TGFBi expanded NK cells
Pediatric Sarcoma, Refractory, Pediatric Sarcoma, Relapsed, Bones and Joints, Sarcoma, Soft Tissue
Children’s Health
FXR Effect on Severe Alcohol-Associated Hepatitis (FRESH) Study (FRESH)
The purpose of this trial is to assess dose related safety, efficacy, and pharmacokinetics (PK) of INT-787 in participants with severe alcohol-associated hepatitis (sAH).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Leticia.Rodriguez@UTSouthwestern.edu
Thomas Cotter
ALL
18 Years to 65 Years old
PHASE2
NCT05639543
STU-2023-0651
Inclusion Criteria:
• Males or females aged 18 to 65 years (inclusive)
• Clinical diagnosis of sAH based on all the following:
• History of ongoing excess alcohol (\>60 g/day \[male\] or \>40 g/day \[female\]) use for ≥6 months, with \<60 days of abstinence prior to the onset of jaundice
• Serum total bilirubin \>3.0 mg/dL
• Aspartate aminotransferase (AST) ≥50 U/L
• AST/Aspartate aminotransferase (ALT) ratio ≥1.5
• Onset of jaundice within prior 8 weeks
• Maddrey's Discriminant Factor (mDF) ≥32 and ≤70
• MELD score 18 to 25 (inclusive)
• Female participants must be postmenopausal, surgically sterile, or, if premenopausal (and not surgically sterile), be prepared to use ≥1 highly effective method of contraception from the initiation of Screening and for 90 days after the last dose of investigational product as follows: * Surgical sterilization (bilateral tubal occlusion, etc.) * Placement of an intrauterine device (IUD) or intrauterine system (e.g., intrauterine hormone-releasing system \[IUS\]) * Combined (estrogen and progesterone containing) hormonal contraceptive associated with inhibition of ovulation: * Oral * Intravaginal * Transdermal * Progesterone-only hormonal contraception associated with inhibition of ovulation: * Oral * Injectable * Implantable * Sexual abstinence: Defined as avoiding all types of activity that could result in conception (pregnancy) from the initiation of Screening and until at least 90 days after the last dose of investigational product
• Male participants who are sexually active with female partners of childbearing potential must agree to use a condom with spermicide and to use 1 other approved method of highly effective contraception from the initiation of Screening and until at least 90 days after the dose of investigational product as listed in Inclusion Criteria #3.
• Male participants must refrain from sperm donation from the initiation of Screening and until at least 90 days after the last dose of investigational product
• Must provide written informed consent and agree to comply with the study protocol. In participants with hepatic encephalopathy which may impair decision-making, consent will be obtained per hospital procedures (e.g., by Legally Authorized Representative).
• Participants must agree to participate in an alcohol use disorder program during the study period, as recommended by the local institution's addiction medicine specialists, including post-hospitalization
Exclusion Criteria:
• Participants taking products containing obeticholic acid in the 30 days prior to randomization
• Participants taking \>2 doses of systemic corticosteroids within 30 days prior to randomization.
• Participants who have been inpatient at a referral hospital for \>7 days prior to transfer.
• Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to use effective birth control during the study), or current or planned breast feeding.
• Abstinence from alcohol consumption for \>2 months before Day 1.
• AST or ALT \>400 U/L.
• mDF \<32 or \>70 at Screening
• MELD score \<18 or \>25 at Screening.
• Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen \[HBsAg\] positive), chronic hepatitis C virus (HCV) RNA positive, drug-induced liver injury (DILI), biliary obstruction, and autoimmune liver disease.
• Current or previous history of hepatocellular carcinoma (HCC)
• History of liver transplantation or currently listed for liver transplant
• Untreated infection (e.g., has not initiated appropriate medical treatment for infection)
• Known positivity for human immunodeficiency virus infection
• Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding that was associated with shock or required transfusion of more than 3 units of blood within 7 days of Screening.
• Kidney injury defined as a serum creatinine \>133 μmol/L (\>1.5 mg/dL) or the requirement for renal replacement therapy.
• Portal vein thrombosis
• Acute pancreatitis or acute gallbladder disease (e.g., cholecystitis)
• Severe, on-going associated disease (e.g., cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease)
• Malignancy within the 2 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection (e.g., basal cell skin cancer). Participants under evaluation for possible malignancy are not eligible.
• Positive urine drug screen (amphetamines, barbiturates, benzodiazepines, cocaine, and opiates) except tetrahydrocannabinol or in the setting of documented prescription medications (e.g., opiates, benzodiazepines, amphetamines, barbiturates), which also include medications prescribed as part of in-patient management. Participants being treated for alcohol withdrawal may be exempt for this reason, verify with Medical Monitor.
• Participated in a clinical research study and received any active investigational product being evaluated for the treatment of sAH within 3 months before Day 1
• Participation in a study of another investigational medicine or device within 30 days before Screening
• Any other condition or clinical laboratory result that, in the opinion of the Investigator, might confound the results, or would impede compliance or hinder completion of the study
DRUG: INT-787, DRUG: Placebo
Alcohol Associated Hepatitis, Liver
Severe Alcohol associated Hepatitis (sAH), Alcoholic Hepatitis (AH), Hepatitis, Alcoholic
UT Southwestern; Parkland Health & Hospital System
A Study to Assess Effectiveness and Safety of Deucravacitinib Compared With Placebo in Participants With Active Systemic Lupus Erythematosus (SLE) (POETYK SLE-1)
The purpose of this study is to evaluate the effectiveness and safety of deucravacitinib compared with placebo in an active moderate to severe Systemic Lupus Erythematosus (SLE) population.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maysa.Ahmed@UTSouthwestern.edu
David Karp
ALL
18 Years to 75 Years old
PHASE3
NCT05617677
STU-2022-0987
Inclusion Criteria
* Diagnosed with Systemic Lupus Erythematosus (SLE) at least 24 weeks before the screening visit.
* Meet the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for SLE.
* One of the following: positive antinuclear antibodies (ANA) ≥ 1:80 at screening OR positive anti dsDNA OR positive anti Smith (anti Sm) as determined by the central laboratory at screening.
* Total Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) score ≥ 6 points and clinical SLEDAI 2K score ≥ 4 points with joint involvement, and/or cutaneous vasculitis, and/or rash.
* Lupus headache, alopecia, organic brain syndrome, and mucosal ulcers must be recorded on SLEDAI 2K, if indicated, but do not count toward the points required for screening at entry.
* At least one SLE background therapy (immunosuppressant and/or antimalarial) is required for ≥ 12 weeks before the screening visit, must be at a stable dose for ≥ 8 weeks before the screening visit, and must remain stable until randomization and throughout study participation.
* Oral corticosteroid (OCS; prednisone or equivalent) background therapy is permitted but not required. For participants taking OCS, the dose must be stable for ≥ 2 weeks before the screening visit, cannot exceed 30 mg/day at screening, and must remain stable until the Week 4 visit. Participants can be on an OCS as well as an antimalarial and/or an immunosuppressant.
Exclusion Criteria
* Diagnosis of drug-induced SLE rather than idiopathic SLE.
* Other autoimmune diseases (eg, multiple sclerosis, psoriasis, inflammatory bowel disease, etc.) are excluded. Participants with type I autoimmune diabetes mellitus, thyroid autoimmune disease, Celiac disease, or secondary Sjögren's syndrome are not excluded.
* SLE overlap syndromes including, but not limited to, rheumatoid arthritis, scleroderma, and mixed connective tissue disease are excluded.
* Active or unstable lupus neuropsychiatric manifestations, including, but not limited to, any condition defined by BILAG A criteria.
* Active, severe Class III, and IV, lupus nephritis that requires or may require treatment with cytotoxic agents or high-dose CS.
* History of congenital or acquired immunodeficiency.
* Known active infection, or any major episode of infection requiring hospitalization or treatment with parenteral (intramuscular or IV) antimicrobial agents (eg, antibiotics antiviral, antifungal, or antiparasitic agents) within 30 days of randomization, or treatment with oral antimicrobial agents within 2 weeks of randomization.
* Currently on any therapy for chronic infection (eg, pneumocystis, herpes zoster, cytomegalovirus, invasive bacterial or fungal infections, or atypical mycobacteria).
* Taking more than 1 immunosuppressant at screening.
* Other protocol-defined Inclusion/Exclusion criteria apply.
DRUG: Deucravacitinib, OTHER: Placebo
Systemic Lupus Erythematosus
Autoimmune Diseases, Immune System Diseases, Connective Tissue Diseases, Immune-mediated Diseases, Active Systemic Lupus Erythematosus, Lupus, SLE, Deucravacitinib, Tyk2, POETYK, POETYK SLE
UT Southwestern; Parkland Health & Hospital System
A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT05614739
STU-2023-0080
Inclusion Criteria:
* Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
* Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
* Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 alteration.
* Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial cancer that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
* Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
* Measurability of disease:
* Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
* Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by RECIST v1.1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country-specific regulations.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Prior Systemic Therapy Criteria:
* Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
* Cohort A2/B1/B2/B3: Participants must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
* FGFR inhibitor specific requirements:
* Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
* Cohort B1: Participants must have been previously treated with a FGFR inhibitor.
* Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.
Exclusion Criteria:
* Participants with primary central nervous system (CNS) malignancy.
* Known or suspected history of uncontrolled CNS metastases.
* Current evidence of corneal keratopathy or retinal disorder.
* Have a history and/or current evidence of extensive tissue calcification.
* Any serious unresolved toxicities from prior therapy.
* Significant cardiovascular disease.
* Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF).
* Active uncontrolled systemic infection or other clinically significant medical conditions.
* Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled. DRUG: LOXO-435, DRUG: Pembrolizumab
Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kaposis sarcoma, 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, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern; Parkland Health & Hospital System
MK-5475-013 INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of MK-5475 (an Inhaled sGC Stimulator) in Adults With PH-COPD
Researchers are looking for ways to treat pulmonary hypertension (PH) caused by chronic obstructive pulmonary disease (COPD). The goal of the study is to learn if people who take MK-5475 can walk farther in 6 minutes at Week 24 compared to people who take placebo.
Call 214-648-5005
studyfinder@utsouthwestern.edu, tatyana.ganz@utsouthwestern.edu
Kelly Chin
ALL
40 Years to 85 Years old
PHASE2
NCT05612035
STU-2023-0403
The key inclusion and exclusion criteria include but are not limited to the following:
Inclusion Criteria:
* Has Group 3.1 pulmonary hypertension chronic obstructive pulmonary disease (PH-COPD) as defined by the Clinical Classification of Pulmonary Hypertension.
* Has a right heart catheterization (RHC) at screening or historical RHC within 12 months before screening that meets hemodynamic criteria.
* Has a physician diagnosis of obstructive lung disease on pulmonary function testing (PFT) performed at screening.
* Has a WHO Functional Class assessment of Class II to IV.
* If on supplemental oxygen, the regimen must be stable.
* Has stable and optimized chronic, baseline COPD-specific therapy.
* If on PDE5 inhibitor, has stable concomitant use (initiated at least 3 months prior to randomization and no change in drug or dosage for at least 3 months prior to randomization) and changes to PDE5 inhibitor dosing is not anticipated during the 24 week Base Period.
* If on antihypertensives and/or a diuretic regimen has stable concomitant use.
* If on anticoagulants has stable concomitant use.
* Is of any sex/gender from 40 to 85 years of age inclusive.
* Female is not pregnant or breastfeeding, and is not of childbearing potential or uses acceptable contraceptive method or abstains from sexual intercourse, or has a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention, or whose history and sexual activity has been reviewed by the investigator.
Exclusion criteria:
* Has Group 1 pulmonary arterial hypertension (PAH), Groups 2, 4 or 5 pulmonary hypertension (PH).
* Has non-COPD related Group 3 PH.
* Has evidence of untreated more than mild obstructive sleep apnea.
* Has significant left heart disease.
* Expects to receive a lung and/or heart transplant from screening through the end of the 24 week Base Period.
* Has evidence of a resting oxygen saturation (SpO2) \< 88%.
* Has experienced a moderate or severe COPD exacerbation within 2 months before randomization.
* Has experienced right heart failure within 2 months before randomization.
* Has uncontrolled tachyarrhythmia.
* Has acute coronary syndrome, undergone coronary artery bypass graft, or percutaneous coronary intervention within 2 months before randomization.
* Has evidence of significant chronic renal insufficiency.
* Has evidence of chronic liver disease, portal hypertension, cirrhosis, or hepatic abnormalities.
* Initiated a pulmonary rehabilitation program within 2 months before randomization.
* Has impairments that limit the ability to perform 6MWT.
* Has history of cancer.
* Is a user of illicit drugs or has a recent history of drug/alcohol abuse or dependence.
* Has used PAH-specific therapies within 2 months of randomization. DRUG: MK-5475, DRUG: Placebo
Pulmonary Hypertension, Chronic Obstructive Pulmonary Disease
UT Southwestern
Selinexor in Maintenance Therapy After Systemic Therapy for Participants with P53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma (XPORT-EC-042)
The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v 1.1\]) after completing at least 12 weeks of platinum-based therapy. A total of 220 participants will be enrolled in the study and randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
ALL
18 Years and over
PHASE3
NCT05611931
STU-2023-0654
Inclusion Criteria:
* At least 18 years of age at the time of signing informed consent.
* Histologically confirmed EC including: endometrioid, serous, undifferentiated, and carcinosarcoma.
* TP53 wt assessed by next generation sequencing (NGS), evaluated by a central vendor.
* Completed a single line, at least 12 weeks of platinum-based therapy (not including adjuvant or neoadjuvant therapy for Stage I-III disease) and achieved confirmed partial or complete response (PR or CR) by imaging, according to RECIST version 1.1. The participants should have received treatment for:
Primary Stage IV disease, defined as:
* had a primary or later debulking surgery during first-line platinum-based therapy with R0 resection (R0 resection indicates a macroscopic complete resection of all visible tumor) and achieved CR after at least 12 weeks platinum-based therapy, OR
* had a primary or later debulking surgery during first-line platinum-based therapy with R1 resection (R1 resection indicates incomplete removal of all macroscopic disease) and achieved PR or CR after at least 12 weeks platinum-based chemotherapy, OR
* had no surgery and achieved PR or CR after at least 12 weeks platinum-based chemotherapy
OR
At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy and/or immunotherapy for Stage I-IV disease), defined as:
* had Stage I - III disease at diagnosis and received, at initial diagnosis, adjuvant chemotherapy and relapsed later. Participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse,
* had Stage I-III disease at diagnosis and did not receive adjuvant chemotherapy at initial diagnosis and relapsed later. Participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
* had Stage IV disease at diagnosis and received initially chemotherapy with or without surgery and relapsed later. At the time of relapse, participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse.
* Previous treatment with anti-programmed cell death protein 1(PD-1) or anti-programmed death-ligand 1(PD-L1) monoclonal antibody and concomitant biologic agents (e.g., bevacizumab, trastuzumab) is allowed.
* Must be able to initiate study drug 3 to 8 weeks after completion of their final dose of chemotherapy.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Participants must have adequate bone marrow function and organ function within 2 weeks before starting study drug as defined by the following laboratory criteria:
* Hepatic function: total bilirubin up to less than (\<) 3\*upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (\<=) 2.5\*ULN in participants without liver metastasis. For participants with known liver involvement of their tumor: AST and ALT (\<=) 5\*ULN
* Hematopoietic function within 1 week: Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.5\*10\^9/liter (L); platelet count \>= 100\*10\^9/L; hemoglobin \>= 9.0 gram per deciliter (g/dL) per local laboratory results
* Renal function: estimated creatinine clearance (CrCl) of \>= 20 milliliter per minute (mL/min), calculated using the standard local formula, as applicable
• In the opinion of the Investigator, the participant must: * Have a life expectancy of at least 12 weeks, and * Be fit to receive investigational therapy * Premenopausal females of childbearing potential must have a negative pregnancy test (serum β-human chorionic gonadotropin test) prior to the first dose of study drug. Female participants of childbearing potential must agree to use highly effective methods of contraception throughout the study and for 90 days following the last dose of study drug. * Written informed consent signed in accordance with federal, local, and institutional guidelines prior to the first screening procedure.
Exclusion Criteria:
* Participants meeting any of the following exclusion criteria are not eligible to enroll in this study:
* Has any uterine sarcomas (carcinosarcomas - not excluded), clear cell or small cell carcinoma with neuroendocrine differentiation
* Received a blood or platelet transfusion during the 2 weeks prior to Cycle 1 Day 1 (C1D1). Participants' hemoglobin must be assessed within 2 weeks of screening and at least 1 week post transfusion
* Concurrent systemic steroid therapy higher than physiologic dose (\> 10 milligram per day \[mg/day\] of prednisone or equivalent). Systemic steroid therapy as pre-medication for taxane is allowed
* Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:
* Not recovered from major surgery \<= 28 days prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous (IV) line for infusion are permitted
* Having ongoing clinically significant anti-cancer therapy-related toxicities CTCAE Grade \> 1, with the exception of alopecia. In specific cases, participants whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor
* Palliative radiotherapy within 14 days of the intended C1D1. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases, provided that the radiotherapy does not involve target lesions, and the reason for the radiotherapy does not reflect evidence of disease progression.
* Any gastrointestinal dysfunctions that could interfere with the absorption of selinexor (e.g., bowel obstruction, inability to swallow tablets, malabsorption syndrome, unresolved nausea, vomiting, diarrhea CTCAE v 5.0 \> grade 1).
* Participants unable to tolerate two forms of antiemetics for at least 2 cycles will not be eligible for the trial.
* Active, ongoing or uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of screening.
* Serious psychiatric or medical condition that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous.
* Previous treatment with an XPO1 inhibitor.
* Stable disease or PD on the post-chemotherapy scan or clinical evidence of progression prior to randomization.
* Participants who received any systemic anticancer therapy including investigational agents \<= 3 weeks (or \<= 5 half-lives of the drug \[whichever is shorter\]) prior to C1D1.
* Major injuries or surgery within 14 days prior to C1D1 and/or planned major surgery during the on-treatment study period.
* Other malignant disease with disease-free \<= 3 years except: curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or ductal carcinoma in situ (DCIS) of the breast.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor, or other agents used in the study.
* Active brain metastases (e.g., stable for \< 8 weeks, no adequate previous treatment with radiotherapy and/or surgery, symptomatic, requiring treatment with anti-convulsant therapy. Corticoid therapy is allowed if administered as stable dose for at least 1 month before randomization).
* Females who are pregnant or lactating.
* Any other life-threatening illness, active medical condition, organ system dysfunction, or serious active psychiatric issue which, in the Investigator's opinion, could compromise the participant's safety or the participant's ability to remain compliant with study procedures. DRUG: Selinexor, DRUG: Matching Placebo for selinexor
Endometrial Cancer, Corpus Uteri
Selinexor, KPT-330, Advanced or Recurrent Endometrial Carcinoma, XPORT-EC, ENGOT-EN20, GOG-3083, XPORT-EC-042, p53 wild-type, Tumor protein 53 wild-type
UT Southwestern; Parkland Health & Hospital System
Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4)
Since its launch in 2004, the overarching aim of the Alzheimer's Disease Neuroimaging Initiative (ADNI) Study has been to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI4 continues the previously funded ADNI1, ADNI-GO, ADNI2, and ADNI3 studies that have combined public/private collaborations between academia and industry to determine the relationships between the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of AD.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Gisella.Rodriguez-Larrain@UTSouthwestern.edu
Trung Nguyen
ALL
55 Years to 90 Years old
NCT05617014
STU-2023-0505
Inclusion Criteria for Newly Enrolled Participants, CN Cohort:
• Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.
• Normal memory function documented by scoring above demographically-adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≥9 for 16 or more years of education
• ≥ 5 for 8-15 years of education
• ≥ 3 for 0-7 years of education
• Note: cut-offs may be modified over time as the field evolves in this area
• Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0. Memory Box score must be 0.
• Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living.
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 years)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria for Newly Enrolled Participants, MCI Cohort
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≤11 for 16 or more years of education
• ≤9 for 8-15 years of education
• ≤6 for 0-7 years of education.
• Note: cut-offs may be modified over time as the field evolves in this area.
• Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5
• General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by the site physician at the time of the screening visit.
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
• Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
• Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen Inclusion Criteria for Newly Enrolled Participants, DEM Cohort
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≤11 for 16 or more years of education
• ≤9 for 8-15 years of education
• ≤6 for 0-7 years of education.
• Note: cut-offs may be modified over time as the field evolves in this area.
• Mini-Mental State Exam score between 20 and 28 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0.5 or 1.0.
• Meets the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Dementia (2011)
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
• Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
• Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen Inclusion Criteria for Newly Enrolled Participants, All Cohorts
• Geriatric Depression Scale score less than 10.
• Age between 55-90 years (inclusive).
• Study partner who has frequent contact with the participant (i.e., minimum average of 2 hours per week) and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).
• Visual and auditory acuity adequate for neuropsychological testing.
• Good general health with no diseases expected to interfere with the study.
• Participant is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile).
• Willing and able to participate in a longitudinal imaging study.
• Must be literate and speak English or Spanish fluently.
• Agrees to collection of blood for GWAS, APOE testing, DNA and RNA testing
• Agrees to collection of blood for biomarker testing.
• The Administrative Core, described in section 9.1.1, will collaborate with leadership from all Cores to review the blood biomarker data from the remote blood cohort and select participants to join the in-clinic cohort. See ADNI4: Remote protocol.
• Agrees to participate in the ADNI study which includes cognitive evaluation, MRI and PET scans.
• Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood. Inclusion Criteria for Rollover Participants, All Cohorts The following additional inclusion criteria apply to all diagnostic categories for rollover participants only:
• Must have been enrolled and followed in one of the following previous ADNI studies: ADNIGO, ADNI2, ADNI3 for at least one year.
• Willing and able to continue to participant in an ongoing longitudinal study. A reduced battery of tests is allowable.
• Study partner may be available who has frequent contact with the participant (i.e., minimum average of 2 hours per week), and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone). Exclusion Criteria for Newly Enrolled Participants, CN Cohort:
• Any significant neurologic disease, such as Parkinson's disease, vascular cognitive impairment/dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities Exclusion Criteria for Newly Enrolled Participants, MCI and DEM Cohorts:
• Any significant neurologic disease other than suspected Alzheimer's disease, such as Parkinson's disease (Parkinsonian symptoms complicating MCI/AD are acceptable), vascular cognitive impairment dementia (multiple lacunes less than or equal to 1.5 cm and/or extensive white matter changes are acceptable), Huntington's disease, normal pressure hydrocephalus, brain tumor (clinically insignificant meningioma acceptable), progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities. Exclusion Criteria for Newly Enrolled Participants, All Cohorts: Additional exclusion criteria apply to all diagnostic categories for newly enrolled participants:
• Screening/Baseline MRI brain scan with evidence of infection, or other clinically significant focal lesions. Participants with cortical strokes, not large enough to distort anatomy, multiple lacunar infarctions or extensive white matter disease are allowed.
• Screening/Baseline MRI brain scan with evidence of large structural abnormalities that would corrupt image analytical pipelines - e.g. large hemispheric infarcts, large areas of encephalomalacia, large arachnoid cysts
• Unable to complete MRIs for any reason (e.g. pacemaker or other implanted metal devices, severe claustrophobia, anxiety which prevents MRI scans, too large to fit, etc.).
• Current major depression, bipolar disorder as described in DMS-IV within the past 1 year. Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
• Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
• History of schizophrenia (DSM-5 criteria).
• History of alcohol or substance disorder within the past 2 years (DSM-5 criteria).
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
• Clinically significant abnormalities in B12, or thyroid function tests that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
• Residence in skilled nursing facility
• Current use of specific psychoactive medications (e.g. certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.), at the discretion of the clinician.
• Current use of any other exclusionary medications.
• Investigational agents are prohibited for five half-lives or one month, whichever time period is longer, prior to entry and for the duration of the trial.
• Participation in clinical studies involving neuropsychological measures being collected more than once time per year.
• Female that is pregnant, lactating, or of childbearing potential.
• Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.
• Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.
• Normal memory function documented by scoring above demographically-adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≥9 for 16 or more years of education
• ≥ 5 for 8-15 years of education
• ≥ 3 for 0-7 years of education
• Note: cut-offs may be modified over time as the field evolves in this area
• Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0. Memory Box score must be 0.
• Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living.
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 years)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria for Newly Enrolled Participants, MCI Cohort
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≤11 for 16 or more years of education
• ≤9 for 8-15 years of education
• ≤6 for 0-7 years of education.
• Note: cut-offs may be modified over time as the field evolves in this area.
• Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5
• General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by the site physician at the time of the screening visit.
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
• Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
• Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen Inclusion Criteria for Newly Enrolled Participants, DEM Cohort
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≤11 for 16 or more years of education
• ≤9 for 8-15 years of education
• ≤6 for 0-7 years of education.
• Note: cut-offs may be modified over time as the field evolves in this area.
• Mini-Mental State Exam score between 20 and 28 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0.5 or 1.0.
• Meets the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Dementia (2011)
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
• Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
• Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen Inclusion Criteria for Newly Enrolled Participants, All Cohorts
• Geriatric Depression Scale score less than 10.
• Age between 55-90 years (inclusive).
• Study partner who has frequent contact with the participant (i.e., minimum average of 2 hours per week) and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).
• Visual and auditory acuity adequate for neuropsychological testing.
• Good general health with no diseases expected to interfere with the study.
• Participant is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile).
• Willing and able to participate in a longitudinal imaging study.
• Must be literate and speak English or Spanish fluently.
• Agrees to collection of blood for GWAS, APOE testing, DNA and RNA testing
• Agrees to collection of blood for biomarker testing.
• The Administrative Core, described in section 9.1.1, will collaborate with leadership from all Cores to review the blood biomarker data from the remote blood cohort and select participants to join the in-clinic cohort. See ADNI4: Remote protocol.
• Agrees to participate in the ADNI study which includes cognitive evaluation, MRI and PET scans.
• Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood. Inclusion Criteria for Rollover Participants, All Cohorts The following additional inclusion criteria apply to all diagnostic categories for rollover participants only:
• Must have been enrolled and followed in one of the following previous ADNI studies: ADNIGO, ADNI2, ADNI3 for at least one year.
• Willing and able to continue to participant in an ongoing longitudinal study. A reduced battery of tests is allowable.
• Study partner may be available who has frequent contact with the participant (i.e., minimum average of 2 hours per week), and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone). Exclusion Criteria for Newly Enrolled Participants, CN Cohort:
• Any significant neurologic disease, such as Parkinson's disease, vascular cognitive impairment/dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities Exclusion Criteria for Newly Enrolled Participants, MCI and DEM Cohorts:
• Any significant neurologic disease other than suspected Alzheimer's disease, such as Parkinson's disease (Parkinsonian symptoms complicating MCI/AD are acceptable), vascular cognitive impairment dementia (multiple lacunes less than or equal to 1.5 cm and/or extensive white matter changes are acceptable), Huntington's disease, normal pressure hydrocephalus, brain tumor (clinically insignificant meningioma acceptable), progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities. Exclusion Criteria for Newly Enrolled Participants, All Cohorts: Additional exclusion criteria apply to all diagnostic categories for newly enrolled participants:
• Screening/Baseline MRI brain scan with evidence of infection, or other clinically significant focal lesions. Participants with cortical strokes, not large enough to distort anatomy, multiple lacunar infarctions or extensive white matter disease are allowed.
• Screening/Baseline MRI brain scan with evidence of large structural abnormalities that would corrupt image analytical pipelines - e.g. large hemispheric infarcts, large areas of encephalomalacia, large arachnoid cysts
• Unable to complete MRIs for any reason (e.g. pacemaker or other implanted metal devices, severe claustrophobia, anxiety which prevents MRI scans, too large to fit, etc.).
• Current major depression, bipolar disorder as described in DMS-IV within the past 1 year. Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
• Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
• History of schizophrenia (DSM-5 criteria).
• History of alcohol or substance disorder within the past 2 years (DSM-5 criteria).
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
• Clinically significant abnormalities in B12, or thyroid function tests that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
• Residence in skilled nursing facility
• Current use of specific psychoactive medications (e.g. certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.), at the discretion of the clinician.
• Current use of any other exclusionary medications.
• Investigational agents are prohibited for five half-lives or one month, whichever time period is longer, prior to entry and for the duration of the trial.
• Participation in clinical studies involving neuropsychological measures being collected more than once time per year.
• Female that is pregnant, lactating, or of childbearing potential.
• Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.
RADIATION: Neuraceq, RADIATION: Amyvid, RADIATION: Tauvid, RADIATION: MK-6240, RADIATION: NAV4694, RADIATION: PI-2620
Mild Cognitive Impairment, Alzheimer Disease, Dementia, Brain and Nervous System
amyloid, plaques, neuroimaging, biomarkers, cognition disorder, early detection, pre-dementia, dementia, Alzheimer's disease, tau, observational
UT Southwestern
Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) After Long-Course Radiation Therapy for Advanced-Stage Rectal Cancers to Improve the Rate of Complete Response and Long-Term Rates of Organ Preservation (JANUS)
This phase II trial compares the effect of irinotecan versus oxaliplatin after long-course chemoradiation in patients with stage II-III rectal cancer. Combination chemotherapy drugs, such as FOLFIRINOX (fluorouracil, irinotecan, leucovorin, and oxaliplatin), FOLFOX (leucovorin, fluorouracil, oxaliplatin, and irinotecan ), and CAPOX (capecitabin and oxaliplatin) 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. FOLFOX or CAPOX are used after chemoradiation as usual treatment for rectal cancer. Giving FOLFIRINOX after chemoradiation may increase the response rate and lead to higher rates of clinical complete response (with a chance of avoiding surgery) compared to FOLFOX or CAPOX after chemoradiation in patients with locally advanced rectal cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nilesh Verma
ALL
18 Years and over
PHASE2
NCT05610163
STU-2023-0870
Inclusion Criteria:
* Stage: Clinical stage II or III rectal adenocarcinoma defined as T4N0 or any T with node positive disease (any T, N+); also T3N0 requiring abdominal perineal resection (APR) or coloanal anastomosis
* Tumor site: Rectum; =\< 12cm from the anal verge
* No prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer within the past 5 years is allowed
* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
\* Therefore, for women of childbearing potential only, a negative pregnancy test (urine or serum according to institutional guidelines) done =\< 14 days prior to registration is required. Female subjects agree to use highly effective contraception combined with an additional barrier method (e.g, diaphragm, with a spermicide) while on study and for \>= 9 months after last dose of study drug, and the same criteria are applicable to male subjects if they have a partner of childbirth potential. Male subject agrees to use a condom and not donate sperm while in this study and for \>= 6 months after the last treatment
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%)
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 50 mL/min
\^3
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN)
* No upper rectal tumors (distal margin of tumor \> 12 cm from the anal verge)
* No recurrent rectal cancer; prior transanal excision, prior distal sigmoid cancer with a low anastomosis
* No known mismatch repair deficient rectal adenocarcinoma
* Human immunodeficiency virus HIV-infected patients on effective anti-retro viral therapy with undetectable viral load within 6 months are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardio toxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification1. To be eligible for this trial, patients should be class 2B or better
* Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study \* Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment DRUG: Capecitabine, DRUG: 5-fluorouracil, DRUG: Leucovorin calcium, DRUG: Irinotecan, DRUG: Oxaliplatin, RADIATION: Long Course Chemoradiotherapy, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Sigmoidoscopy, PROCEDURE: biopsy
Locally Advanced Rectal Carcinoma, Stage II Rectal Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Rectum
UT Southwestern; Parkland Health & Hospital System
Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE): Shionogi Protease Inhibitor (Ensitrelvir)
Treatments are needed to improve outcomes among patients hospitalized for COVID-19, including direct-acting antiviral (DAA) agents to mitigate the pathology driven by ongoing viral replication. This trial will evaluate S-217622 (ensitrelvir), an anti-SARS-CoV2 3C-like protease inhibitor (PI) developed by Shionogi \&; Co. Ltd. The study design is a randomized, placebo-controlled, multi-center international clinical trial that will evaluate the clinical efficacy of ensitrelvir when given in addition to standard of care (SOC) for inpatients with COVID-19. The SOC will be determined by local established guidelines and may include additional DAA (e.g., remdesivir) and immunomodulatory treatment strategies. Certain SOC treatments will be pre-specified prior to randomization.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Olakunbi.Latona@UTSouthwestern.edu
Mamta Jain
ALL
18 Years and over
PHASE3
NCT05605093
STU-2022-1124
Inclusion Criteria:
* Age ≥18 years.
* Informed consent for trial participation.
* Hospital admission (or boarding in an emergency department or other area awaiting hospital admission) with signs and/or symptoms of a respiratory infection.
* Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non- NAT test \[list of approved tests is in the PIM\] collected within the prior 14 days.
* Onset of symptoms attributable to SARS-CoV2 infection occurred within 14 days before randomization.
* Hospitalized for the management of COVID-19, with signs and/or symptoms suggestive of lower respiratory tract infection.
Exclusion Criteria:
* The patient is expected to be discharged from the hospital within the next 24 hours.
* Medical condition other than the acute respiratory infection (and its manifestations) that is likely to result in death within 7 days of randomization.
* Use of a strong CYP3A inducer within 14 days prior to enrollment
* Moribund condition, defined as prior cardiac arrest during this hospitalization and life expectancy less than 48 hours of randomization.
* Patient undergoing comfort care measures only such that treatment focuses on end-of- life symptom management over prolongation of life.
* Expected inability or unwillingness to participate in study procedures.
* In the opinion of the investigator, participation in a trial is not in the best interest of the patient.
* Allergy to investigational agent or vehicle
* Use of a concomitant medication that is contraindicated due to a drug-drug interaction with S-217622
* Moderate to severe hepatic impairment (i.e., Child-Pugh class B or C) or acute liver failure.
* Known estimated glomerular filtration rate (eGRF) \<30 mL/min/1.73m 2
* Continuous renal replacement therapy or chronic dialysis
* Current pregnancy
* Current breastfeeding and unwillingness to defer breastfeeding for 30 days after the last dose of investigational agent.
* Women of child-bearing potential who are unwilling to abstain from sexual intercourse with men or practice appropriate contraception through 30 days from the last dose of the investigational agent.
* Men who are unwilling to abstain from sexual intercourse with women of child- bearing potential or to use barrier contraception through 30 days from the last dose of the investigational agent.
* Inability to take investigational agent in tablet form by mouth. DRUG: Shionogi Protease Inhibitor (S-217622), DRUG: placebo
COVID-19, Other
UT Southwestern; Parkland Health & Hospital System
Novel Targeted Radiotherapy in Pediatric Patients With Inoperable Relapsed or Refractory HGG
The purpose of this dose finding study is to evaluate the safety and efficacy of 2 different dose levels of CLR 131 in children, adolescents and young adults with relapsed or refractory high-grade glioma (HGG).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
10 Years to 25 Years old
PHASE1
NCT05610891
STU-2023-1117
Inclusion Criteria:
* Previously confirmed (histologically or cytologically) high grade glioma that is clinically or radiographically suspected to be relapsed, refractory, or recurrent
* ≥ 10 years of age and ≤ 25 years of age at time of consent/assent
* If ≥ age 16 years, Karnofsky performance status of ≥ 60. If \< age 16 years, Lansky performance status ≥ 60
* Platelets ≥ 75,000/μL (last transfusion, if any, must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
* Absolute neutrophil count ≥ 750/μL
* Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
* Using the bedside Schwartz formula, estimated GFR (creatinine clearance) \> 60 ml/min/1.73m2
* Alanine aminotransferase \< 3 × ULN
* Bilirubin \< 2 × ULN
* At least 1 measurable intracranial lesion with longest diameter of at least 10 mm on any imaging sequence.
* Patients with previously known neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator's discretion.
* If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for three weeks prior to registration) or on a steroid tapering regimen. Initiation of steroids per routine care immediately prior to CLR 131 dosing is acceptable
* Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol.
* Patient or his or her legal representative has the ability to read, understand, and provide written informed consent for the initiation of any study-related procedures.
* Female patients of childbearing potential must have a negative pregnancy test at screening and within 24 hours of dosing. It is recommended that female caregivers of childbearing potential have a negative pregnancy test within one week of dosing.
* Patients of childbearing potential must practice an effective method of birth control while participating on this study to avoid possible harm to the fetus.
Exclusion Criteria:
* Antitumor therapy or investigational therapy, within 3-half-lives of the agent preceding the present study. For certain types of radiation (craniospinal, total abdominal, whole lung \[spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study\]), at least 3 months must have elapsed. Palliative focal radiation to non-target lesions should be completed at least 2 weeks prior to dosing. Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial
* History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol's solution, etc.)
* Any other concomitant serious illness or organ system dysfunction (including cardiac and pulmonary dysfunction) that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
* Major surgery within 6 weeks of enrollment unless delay in therapy poses unacceptable risk to the patient due to clinical progression (enrollment o such patients should be discussed with Medical Monitor)
* Known history of human immunodeficiency virus or uncontrolled, serious, active infection
* Pregnancy or breast-feeding DRUG: CLR 131
High-Grade Glioma, Brain and Nervous System
Children’s Health
A Trial Comparing Unrelated Donor BMT with IST for Pediatric and Young Adult Patients with Severe Aplastic Anemia (TransIT, BMT CTN 2202) (TransIT)
Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant. Regular treatment for patients with aplastic anemia who have a matched sibling (brother or sister), or family donor is a bone marrow transplant. Patients without a matched family donor normally are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bone marrow transplant (BMT) is used as a secondary treatment in patients who did not get better with IST, had their disease come back, or a new worse disease replaced it (like leukemia). This trial will compare time from randomization to failure of treatment or death from any cause of IST versus URD BMT when used as initial therapy to treat SAA. The trial will also assess whether health-related quality of life and early markers of fertility differ between those randomized to URD BMT or IST, as well as assess the presence of marrow failure-related genes and presence of gene mutations associated with MDS or leukemia and the change in gene signatures after treatment in both study arms. This study treatment does not include any investigational drugs. The medicines and procedures in this study are standard for treatment of SAA.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Laurie.Rodgers-Augustyniak@childrens.com
Tiffany Simms-Waldrip
ALL
0 Years to 25 Years old
PHASE3
NCT05600426
STU-2022-0964
Inclusion Criteria:
To be eligible to participate in the randomized trial, an individual must meet all the following criteria:
• Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian.
• Age ≤25 years old at time of randomized trial consent.
• Confirmed diagnosis of idiopathic SAA, defined as:
• Bone marrow cellularity \<25%, or \<30% hematopoietic cells.
• Two of three of the following (in peripheral blood): neutrophils \<0.5 x 10\^9/L, platelets \<20 x 10\^9/L, absolute reticulocyte count \<60 x 10\^9/L or hemoglobin \<8 g/dL.
• No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing).
• At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution).
• In the treating physician's opinion, no obvious contraindications precluding them from BMT or IST.
Exclusion Criteria:
• Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic isoamylase testing is not useful in children \<3). Other testing per center may be performed to exclude IBMFS.
• Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.
• Known severe allergy to ATG.
• Prior allogeneic or autologous stem cell transplant.
• Prior solid organ transplant.
• Infection with human immunodeficiency virus (HIV).
• Active Hepatitis B or C. This only needs to be excluded in patients where there is clinical suspicion of hepatitis (e.g., elevated LFTs).
• Female patients who are pregnant or breast-feeding.
• Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.
• Disease modifying treatment prior to study enrollment, including but not limited to use of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportive care measures such as G-CSF, blood transfusion support and antibiotics are allowable
DRUG: cyclosporine, PROCEDURE: Matched Unrelated Donor Hematopoetic Stem Cell Transplant, DRUG: horse anti-thymocyte globulin (ATG), DRUG: rabbit anti-thymocyte globulin (ATG), DRUG: Methotrexate, DRUG: Fludarabine, DRUG: Cyclophosphamide, RADIATION: low-dose total body irradiation (TBI), PROCEDURE: Immunosuppressive Therapy (IST)
Severe Aplastic Anemia
Children’s Health
A Phase 2a, Single-dose, Open-label Study to Evaluate Diagnostic Performance and Safety of Pegsitacianine, an Intraoperative Fluorescence Imaging Agent for the Detection of Cancer, in Patients With Unknown Primary Head and Neck Cancer (ILLUMINATE STUDY)
This is a non-randomized, open-label, single-center, safety and imaging feasibility study of Pegsitacianine, an intraoperative fluorescence imaging agent.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Baran Sumer
All
18 Years to 99 Years old
Phase 2
NCT05576974
STU-2022-0460
Inclusion Criteria:
• Adults ≥18 years of age
• Biopsy-confirmed diagnosis, for primary or recurrent disease (or high clinical suspicion in the opinion of the Investigator)
• Part 1: Stage 1 to 4 HNSCC
• Part 2: UPC squamous cell carcinoma of the head and neck with metastatic disease to at least a single cervical node, AND no biopsy proven evidence of the primary cancer's location.
• Acceptable hematologic status (as standard surgery protocol requires, as determined by the Investigator), kidney function and liver function. Elevations of creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin >1.5× the upper limit of normal [ULN] must be determined to be not clinically significant by the Investigator and approved by the Medical Monitor.
• Documented negative serum pregnancy test for women of childbearing potential (i.e., premenopausal women with intact reproductive organs and women <2 years after menopause)
• Male patients and female patients of child-bearing potential (i.e., premenopausal women with intact reproductive organs and women <2 years after menopause) must agree to and comply with using medically acceptable contraception including surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation), intrauterine device, oral contraceptive, contraceptive patch, long acting injectable contraceptive, partner's vasectomy, double-barrier method (condom or diaphragm plus spermicide or condom plus diaphragm), or abstinence during the trial and for 6 months thereafter
• Agree to abstain from alcohol consumption from 72 hours before Pegsitacianine administration through completion of Study Day 10 (±48 hours) visit in Part 1 and Part
• 7. Adequate potential for follow up
Exclusion Criteria:
• Tumors at sites of which the surgeon would assess that in vivo intraoperative imaging would not be feasible.
• Life expectancy <12 weeks
• Karnofsky Performance Status <70%
• Hepatic impairment (Child-Pugh score >5) or significant liver disease including active hepatitis or cirrhosis
• Lab values or any sign, symptom, or medical condition that in the opinion of the PI would prevent surgical resection
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Pregnant or lactating women
• Receiving or planned to receive, during the duration of the study, concomitant medication with a high chance of hepatotoxicity, as judged by the PI based on standard protocols within the study center
• Alcohol consumption within 72 hours before Pegsitacianine administration
• Received an investigational agent within the shorter of 5 half-lives or 30 days before Pegsitacianine dosing
• Inability to adhere to the schedule of assessments or any circumstance that would interfere with the validity of assessments performed in the study
• The PI considers that the patient should not participate in the study
Drug: Pegsitacianine
Head and Neck Cancer, Unknown Primary Cancer, Head and Neck Squamous Cell Carcinoma, Head and Neck
UT Southwestern
Risk Indicators of Sarcoidosis Evolution-Unified Protocol (RISE-UP)
The purpose of this study is to develop prediction models that can prognosticate patients with sarcoidosis using clinical data and blood markers that can be obtained during a clinic visit.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Fabiola.Gianella@UTSouthwestern.edu
Connie Hsia
All
19 Years and over
NCT05567133
STU-2022-0683
Inclusion Criteria:
• Adults with a diagnosis of sarcoidosis over the age of 18
• Case definition: we will follow the 1999 statement on sarcoidosis published by the American Thoracic Society for diagnosis which includes tissue biopsy confirmation and exclusion of alternative diagnoses including beryllium sensitization/chronic beryllium disease, mycobacterial, viral, and/or fungal infection
Exclusion Criteria:
• Inability to tolerate study procedures as determined by the investigator
• Pregnant or breastfeeding
• Concurrent medical diagnoses that would influence the expression of biomarkers will be considered an exclusion criterion. This includes diseases such as common variable immunodeficiency, HIV infection, or autoimmune diseases
• Concurrent interstitial lung diseases such as hypersensitivity pneumonitis or idiopathic pulmonary fibrosis
• Hematocrit (Packed Cell Volume) < 25%
Sarcoidosis, Pulmonary
sarcoid, lung, immune
UT Southwestern; Parkland Health & Hospital System
Cognitive Outcomes of Brain Stimulation As a Later-in-Life Treatment (COBALT)
This is a pilot study being done to attempt to improve episodic memory problems in persons with mild cognitive impairment (MCI) or dementia. The pre-supplemental motor area (preSMA) and dorsal anterior cingulate cortex (dACC) have been shown to play a role in episodic memory and language retrieval. Prior studies have suggested that neurostimulation targeting this region can improve episodic memory and word recall. The purpose of this study is to examine the efficacy of high-definition transcranial direct current stimulation (HD-tDCS) to the preSMA/dACC region and its influence on word retrieval and other cognitive functions in patients with MCI or dementia. Entraining the preSMA/dACC circuit with 10 sessions of HD-tDCS will allow us to study whether neurostimulation may be an effective treatment.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hannah.Cabrera@UTSouthwestern.edu
Christian LoBue
ALL
55 Years and over
NA
NCT05564715
STU-2022-0799
Inclusion Criteria:
Active diagnosis of mild cognitive impairment or dementia, Female and male subjects, All races/ethnicities, Age 55 years and older, Fluent in English,
Exclusion Criteria:
Lifetime history of major neurologic syndromes (e.g., epilepsy, brain tumor, etc), Substance use disorder within the past year, Has metal fragments in skull/head, Current vision or hearing impairment that interferes with testing, Current medication use known to alter HD-tDCS reactivity DEVICE: NeuroElectric StarStim, DEVICE: Sham Treatment
Mild Cognitive Impairment, Dementia, Amnestic Mild Cognitive Impairment - aMCI, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System