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407 Study Matches
Perioperative FLOT(D) With Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) in Esophageal Cancer
The goal of this clinical trial is to learn the safety of the addition of PULSAR radiation to standard of care chemotherapy and immunotherapy in people with esophageal and gastroesophageal junction cancer and to determine the safest dose of radiation that can be used. Participants in this study will be undergoing clinically scheduled procedures. In addition to the standard of care visits and treatments, there will be additional visits and assessments with radiation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Timothy Brown
ALL
18 Years to old
PHASE1
NCT07700420
STU20250653
Inclusion Criteria:
• At least 18 years of age at date of enrollment. Both men and women and members of all races and ethnic groups will be included.
• Willing and able to provide written informed consent.
• Pathologic diagnosis of esophageal or gastroesophageal junction adenocarcinoma. GEJ cancer includes Siewart types 1 and 2 tumors. Siewart type 3 is also eligible as long as the patient is intended to be treated in the same way as for type 1 and 2 tumors (i.e. candidate for FLOT-(D), resectable, amenable to radiation)
• T1N+ or T2-4N(any) by the American Joint Committee on Cancer staging manual 8th edition
• Primary tumor (and lymph nodes) that appear to be resectable in the opinion of an experienced thoracic surgeon or surgical oncologist 19.
• Measurable disease by RECIST 1.1 is not a requirement in order to enroll on this study. Those who have measurable disease at baseline will be followed by RECIST 1.1 criteria at time of restaging.
• Primary tumor (and applicable nodal sites) that appears amenable to radiation in the opinion of an experienced radiation oncologist.
• Eastern cooperative Oncology Group (ECOG) performance status of 0-1
• No prior systemic treatment or radiation for esophageal/GEJ adenocarcinoma. Patients who have received prior endoscopic therapies with subsequent recurrence necessitating curative-intent surgery will be eligible for enrollment.
• Adequate organ and marrow function as defined below:
• 0 ANC ≥1500/mL 10.1 Platelet ≥100,000/mL 10.2 Total Bilirubin ≤ 1.0 x the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.
• 3 AST and/or ALT both ≤ 1.5x ULN with alkaline phosphatase ≤2.5x ULN 10.4 Creatinine Clearance ≥ 30 mL/min by Cockroft Gault
• All men, as well as women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first dose of radiation through 120 days after completion of adjuvant chemotherapy or immunotherapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 11a. A woman of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
• Patients with adenosquamous cell carcinoma, squamous cell carcinoma, GI stromal tumor, or neuroendocrine tumor (any grade) of the esophagus or GEJ.
• Receipt of prior chemotherapy, radiotherapy, or both for esophageal or gastroesophageal junction cancer (any type).
• Any other active malignancies besides localized skin cancers or in situ carcinomas. Patients with localized prostate or breast cancers who have been stable for ≥ 6 months on adjuvant therapy without evidence of active disease will be eligible to enroll on this study. Patients with a history of cancer that has not been active in the last 5 years may be included but only after consultation with the principal investigator.
• Prior RT to the chest or abdomen (not esophagus/GEJ) that would, in the opinion of a radiation oncologist, limit the safety of PULSAR.
• Known dihydropyrimidine dehydrogenase (DPYD) intermediate or poor metabolizer phenotype where administration of full dose 5-fluoruracil would be prohibitively toxic. It is not a requirement to test DPYD deficiency prior to enrollment. Patients found to be DPYD intermediate or poor metabolizers through the course of standard of care evaluation will be removed from the protocol and followed for DLTs. These patients will be replaced.
• Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements or that would be prohibitive of a surgical resection in the opinion of a surgical oncologist or thoracic surgeon.
• Chemotherapy, or other systemic cancer therapy for non-esophageal or GEJ cancer within 52 weeks prior to starting study treatment (with the exception of long-term adjuvant therapy for curative-intent prostate or breast cancer, as defined above).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to FLOT chemotherapy, durvalumab or other agents used in study.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Unwilling or unable to undergo placement of chest wall mediport for chemotherapy administration.
• Any autoimmune condition requiring immunosuppression beyond physiologic doses of steroids will not be eligible for receipt of durvalumab. Patient would still be eligible for enrollment for receipt of perioperative FLOT only and can enroll on this study while receiving FLOT.
• Requirement of prednisone 10 mg (or prednisone equivalent) or more daily for any reason (Inhalational steroids for chronic obstructive pulmonary disease, asthma, or the like, is allowable). Patient would still be eligible for enrollment for receipt of perioperative FLOT only if they are meeting all other eligibility criteria.
• Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
RADIATION: PULSAR- Personalized Ultra-fractionated Stereotactic Ablative Radiotherapy, DRUG: FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)(D)
Gastro-esophageal Junction (GEJ) Cancer, Esophagus Cancer, Esophagus, Other Digestive Organ
UT Southwestern
Adaptive Dosing of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma
The goal of this clinical trial is to learn if immunotherapy including nivolumab plus ipilimumab is effective and safe in treating hepatocellular carcinoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years to old
PHASE2
NCT07689175
STU20261069
Inclusion Criteria:
• Patient must have a diagnosis confirmed by histology or clinically by the American Association for the Study of Liver Diseases (AASLD) criteria in patients with cirrhosis. Known fibrolamellar HCC or combined HCC-cholangiocarcinoma will be excluded.
• Patients may not have received any prior anti-PD-1/L1 or anti-CTLA-4 therapies for the treatment of advanced HCC.
• Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
• Child-Pugh Score B7-8
• Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST v.1.1.
• Prior locoregional therapy is allowed provided the target lesion has increased in size ≥25% since the cessation of locoregional therapy or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion.
• Age ≥ 18 years.
• ECOG performance score 0-2
• Adequate organ and marrow function as defined below: Platelet count ≥ 40,000/mm3 Hgb ≥ 8 g/dl INR ≤ 2 AST, ALT ≤ 5 times ULN Calculated creatinine clearance (CrCl) ≥ 35 mL/min. CrCl can be calculated using the Cockcroft-Gault method. Albumin ≥ 2.0 g/dl
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 10a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). 11\. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Prior solid organ transplant.
• Hypersensitivity to IV contrast; not suitable for pre-medication.
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Active autoimmune disease that requires current systemic treatment (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for conditions that, in the investigator's opinion, do not have a substantial hazardous risk such as asthma, and cutaneous and musculoskeletal rheumatologic conditions.
• Known human immunodeficiency virus infection (testing not required) in a patient not on antiretroviral therapy and detectable viral load.
• Prior malignancy that required systemic treatment within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer. Preneoplastic or malignant diagnoses that are indolent in nature and do not require active systemic treatment are not excluded.
• If a participant has symptomatic or clinically active brain metastases including leptomeningeal disease, they must be excluded if: * Has evidence of progression by neurologic symptoms * Has metastatic brain lesions that require immediate intervention. * Has carcinomatous meningitis, regardless of clinical stability
• Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Prisoners or subjects who are involuntarily incarcerated.
• Has significant dementia or other mental condition that precludes the participant's ability to consent to the study.
DRUG: Nivolumab, DRUG: Ipilimumab (3 mg/kg)
Hepatocellular Carcinoma (HCC), Liver
UT Southwestern
Privosegtor Investigation in Optic Neuropathies Efficacy Evaluation Research (PIONEER-1)
The goal of this clinical trial is to evaluate the safety and efficacy of privosegtor, a neuroprotective candidate, in patients diagnosed with optic neuritis (ON). Researchers will compare privosegtor and the standard of care (methylprednisolone) to a placebo and standard of care (methylprednisolone).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Stephanie.Morales@UTSouthwestern.edu
Ruben Jauregui
ALL
18 Years to 50 Years old
PHASE3
NCT07623668
STU20260769
Key
Inclusion Criteria:
* Adult men and women (aged 18 to 50 years) with the first episode of ON in the study eye, associated with unilateral visual loss.
* Onset of visual loss symptoms in the previous 12 days before first administration of study treatment.
Key Exclusion Criteria:
\- Have a history or presence of any disorder or condition that may, in the opinion of the Investigator, likely interfere with the interpretation of the study results or participant safety DRUG: Privosegtor, DRUG: Methylprednisolone, OTHER: Placebo
Optic Neuritis
Optic Neuritis, ON, AON, Optic Neuropathy, Multiple Sclerosis, MS, Vision Loss, LCVA, Low Contrast Visual Acuity, Low Contrast Sensitivity, Privosegtor, OCS-05
UT Southwestern
A Phase 2, Open-Label, Single-Arm Trial of FT819 in Participants With Lupus Nephritis (RECLAIM-LN)
The primary objective of this trial is to evaluate the efficacy and safety of FT819, comprised of allogeneic T cells that express a CD19-targeted CAR, following bendamustine administration in participants with refractory moderate-to-severe lupus nephritis, as assessed by the proportion of participants who achieve complete renal response (CRR) at Week 26.
Call 214-648-5005
studyfinder@utsouthwestern.edu, ivan.sy@childrens.com
Samuel John
ALL
12 Years to 70 Years old
PHASE2
NCT07570862
STU20260716
INCLUSION CRITERIA:
* Age ≥12 to ≤70 years
* Diagnosis of SLE per EULAR/ACR 2019 classification criteria
* Biopsy-proven proliferative Class III or IV LN, with or without concomitant Class V involvement, based on the 2003/2018 ISN/RPS classification
* Positivity for at least one of the following autoantibodies at screening:
• Antinuclear antibody (ANA)
• Anti-double-stranded DNA (anti-dsDNA) or
• Anti-Smith antibody * Active disease, defined as: a. Evidence of SLE activity, defined as either: i. SLEDAI-2K ≥6 or ii. At least 1 BILAG A or 2 BILAG B scores for SLE-related organ involvement; and b. Evidence of renal involvement, defined as UPCr ≥1 g/g; and c. Moderate-to-severe renal disease with investigator's impression that improvement is possible * Refractory to ≥2 systemic immunosuppressive therapies for the treatment of LN EXCLUSION CRITERIA: * Evidence of inadequate organ function during the screening period * Active central nervous system (CNS) symptoms attributable to autoimmune disease within 12 months prior to trial intervention * History of or current renal diseases (other than LN) that, in the opinion of the investigator, could interfere with assessment of LN or confound evaluation of disease activity * Receipt of dialysis (hemodialysis or peritoneal dialysis) within 12 weeks of trial intervention * Irreversible organ damage related to underlying disease (e.g., ESRD) where, in the opinion of the investigator, CD19 CAR T-cell therapy would be unlikely to benefit the participant * History of malignancy in the prior 5 years * Known allergy to the following FT819 components: albumin (human) or DMSO * History of intolerance or contraindication to bendamustine * Body weight \<30 kg * Any medical condition, clinical laboratory abnormality, or nonmedical/social issue that, per investigator or medical monitor judgement, precludes safe participation in and completion of the trial or that could affect compliance with protocol conduct or interpretation of results
• Antinuclear antibody (ANA)
• Anti-double-stranded DNA (anti-dsDNA) or
• Anti-Smith antibody * Active disease, defined as: a. Evidence of SLE activity, defined as either: i. SLEDAI-2K ≥6 or ii. At least 1 BILAG A or 2 BILAG B scores for SLE-related organ involvement; and b. Evidence of renal involvement, defined as UPCr ≥1 g/g; and c. Moderate-to-severe renal disease with investigator's impression that improvement is possible * Refractory to ≥2 systemic immunosuppressive therapies for the treatment of LN EXCLUSION CRITERIA: * Evidence of inadequate organ function during the screening period * Active central nervous system (CNS) symptoms attributable to autoimmune disease within 12 months prior to trial intervention * History of or current renal diseases (other than LN) that, in the opinion of the investigator, could interfere with assessment of LN or confound evaluation of disease activity * Receipt of dialysis (hemodialysis or peritoneal dialysis) within 12 weeks of trial intervention * Irreversible organ damage related to underlying disease (e.g., ESRD) where, in the opinion of the investigator, CD19 CAR T-cell therapy would be unlikely to benefit the participant * History of malignancy in the prior 5 years * Known allergy to the following FT819 components: albumin (human) or DMSO * History of intolerance or contraindication to bendamustine * Body weight \<30 kg * Any medical condition, clinical laboratory abnormality, or nonmedical/social issue that, per investigator or medical monitor judgement, precludes safe participation in and completion of the trial or that could affect compliance with protocol conduct or interpretation of results
BIOLOGICAL: FT819
Lupus Nephritis, Systemic Lupus Erythematosus, SLE - Systemic Lupus Erythematosus, Lupus Nephritis - WHO Class III, Lupus Nephritis - WHO Class IV
FT819, Fate Therapeutics, Allogeneic CAR T, CD19 - targeted therapy, Lupus Nephritis, Systemic Lupus Erythematosus
Children’s Health
A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With α- or β-Non-Transfusion-Dependent Thalassemia (ENERGIZEKids)
The primary objective of this study is to compare the effect of mitapivat versus placebo on anemia in pediatric participants with alpha- or beta-non-transfusion-dependent thalassemia.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Laurie.Rodgers-Augustyniak@childrens.com
Kathryn Dickerson
ALL
1 Year to 17 Years old
PHASE3
NCT07517133
STU20260644
Inclusion Criteria:
* Written informed consent/assent from the participant (or their legally authorized representative, parent(s), or legal guardian) must be obtained before any study-related procedures are conducted and participants must be willing to comply with all study procedures for the duration of the study.
* Aged 1 to \<18 years and weighing at least 7 kilograms (kg) at the time of providing informed consent/assent.
* Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, hemoglobin E (HbE)/β-thalassemia, or α-thalassemia/hemoglobin H (HbH) disease) based on Hemoglobin (Hb) electrophoresis, Hb high-performance liquid chromatography, and/or DNA analysis from the participant's medical record. If this information is not available from the participant's medical record, the test(s) can be performed by a local laboratory during the Screening Period. If a local laboratory is unable to perform the test(s), results from the comprehensive α- and β-globin genotyping performed by the study central laboratory can be used.
* Hb concentration ≤10.0 grams per deciliter (g/dL) \[100.0 grams per liter (g/L)\], based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period.
* Non-transfusion dependent, defined as ≤5 transfusion episodes (also referred to as "transfusion events") during the 24-week period before randomization and no red blood cells (RBC) transfusions ≤8 weeks before providing informed consent/assent and no RBC transfusions during the Screening Period.
* If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization.
* Female participants who have attained menarche must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of informed consent/assent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can include an acceptable barrier method.
Exclusion Criteria:
* Pregnant or breastfeeding.
* Documented history of homozygous or heterozygous hemoglobin S (HbS) or hemoglobin C (HbC).
* Prior exposure to gene therapy or prior bone marrow or stem cell transplantation, including any prior exposure to myeloablative chemotherapy.
* Any conditions other than thalassemia expected to affect sexual maturation.
* Currently receiving treatment with luspatercept; the last dose must have been administered ≥18 weeks before randomization.
* Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥18 weeks before randomization.
* History of malignancy (active or treated) ≤5 years before providing informed consent/assent, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ.
* History of active and/or uncontrolled cardiac or pulmonary disease or clinically relevant QT prolongation within 6 months before providing informed consent/assent.
* Hepatobiliary disorders, including but not limited to:
* Liver disease with histopathological evidence or clinical diagnosis of cirrhosis or severe fibrosis.
* Clinically symptomatic cholelithiasis or cholecystitis (prior cholecystectomy is not exclusionary).
* History of drug-induced cholestatic hepatitis.
* Aspartate Aminotransferase (AST) \>2.5\*Upper Limit of Normal (ULN) (unless due to hemolysis and hepatic iron deposition) and Alanine Transaminase (ALT) \>2.5\*ULN (unless due to hepatic iron deposition).
* Renal dysfunction as defined by an estimated glomerular filtration rate \<60 milliliters per minute (mL/min)/1.73-meter square (m\^2).
* Nonfasting triglycerides \>215 milligrams per deciliter (mg/dL) \[5 millimole per liter (mmol/L)\].
* Active infection requiring systemic antimicrobial therapy at the time of providing informed consent/assent. If antimicrobial therapy is required during the Screening Period, screening procedures should not be performed while antimicrobial therapy is being administered, and the last dose of antimicrobial therapy must be administered ≥7 days before randomization.
* Participants with known active hepatitis B or hepatitis C virus infection.
* Participants with known human immunodeficiency virus (HIV) infection.
* History of major surgery (including splenectomy) ≤16 weeks before providing informed consent/assent and/or a major surgical procedure planned during the study.
* Current enrollment or past participation (within ≤12 weeks or a timeframe equivalent to 5 half-lives of the investigational study drug before administration of the first dose of study drug, whichever is longer) in any other clinical study involving an investigational treatment or device.
* Receiving strong Cytochrome3A4/5 (CYP3A4/5) inhibitors that have not been stopped for ≥5 days or a timeframe equivalent to 5 half-lives (whichever is longer), or strong CYP3A4/5 inducers that have not been stopped for ≥4 weeks or a timeframe equivalent to 5 half-lives (whichever is longer), before randomization.
* Receiving anabolic steroids that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed; the testosterone dose and preparation must be stable for ≥12 weeks before randomization.
* Known allergy, or other contraindication, to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and the Opadry filmcoat \[hypromellose, titanium dioxide, lactose monohydrate triacetin, and FD\&C Blue #2\]).
* Any medical, hematological, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are:
* Participants who are institutionalized by regulatory or court order.
* Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor). DRUG: Mitapivat, DRUG: Placebo Matching Mitapivat
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
Children’s Health
Immune Modulation During Palynziq® Treatment in Adults (IMPALA)
Study 165-401 is a Phase 4, open-label study designed to examine the concomitant use of methotrexate (MTX) to suppress immune responses to Palynziq and improve tolerability and efficacy in adults with PKU.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Juana.Luevano@UTSouthwestern.edu
Markey McNutt
ALL
18 Years to 65 Years old
PHASE4
NCT07477691
STU20252279
Inclusion Criteria:
* Adults between 18 and 65 years old
* Have a confirmed diagnosis of phenylketonuria (PKU)
* Are in generally good health based on medical evaluation
* Are willing and medically eligible to receive Palynziq and methotrexate (MTX) Cohort A: Have never taken Palynziq before and are willing to start it during the study Cohort B: Have blood \> 600 μmol/L after taking Palynziq for at least 24 weeks, are on a daily dose of at least 20mg and unable to increase the dose further
* Agree to use required contraception if they or their partner could become pregnant
* Are willing to carry two epinephrine devices at all times during Palynziq treatment
Exclusion Criteria:
* Pregnant, breastfeeding, planning to become pregnant, planning to father a child, or not using effective birth control if applicable
* Have a known severe allergy or hypersensitivity reaction to methotrexate (MTX), Palynziq, or other PEG-containing medications
* Have a serious active infection or a history of severe or recurrent infections
* Have significant medical conditions that may affect safety or participation (such as serious heart, lung, liver, kidney, immune, neurological, psychiatric, or cancer-related conditions)
* Have a history of substance or alcohol abuse within the past 12 months
* Have had an organ transplant or are taking chronic immunosuppressive medications
* Are currently taking medications that are not allowed in the study, including other PKU treatments besides Palynziq
* Are using, or plan to use, injectable PEG-containing medications other than Palynziq during the study
* Have major surgery planned during the study participation period
* Are currently participating in another clinical study involving Palynziq
* In the opinion of the study doctor, are not a suitable candidate for the study or may have difficulty complying with study requirements BIOLOGICAL: Pegvaliase, DRUG: Methotrexate
Phenylketonuria
PKU, Phenylketonuria, Pegvaliase, Palynziq, Methotrexate, Immune Response, Safety, Immune Modulation, BMN 165-401, Hyperphenylalaninemia, Enzyme Substitution Therapy, Pharmacologic Immunosuppression
UT Southwestern; Children’s Health
A First-in-human (FIH), Phase 1 Study of ML261, an Autologous Potency Enhanced Anti-DLL3 CAR T Cell Therapy, in Participants With R/R SCLC or Select NECs (SPECTRAL-1)
This is a first-in-human (FIH), open-label, Phase 1 study designed to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of ML261, an autologous potency enhanced anti-DLL3 CAR T cell therapy, in participants with R/R SCLC or select NECs
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Benjamin Drapkin
ALL
18 Years to old
PHASE1
NCT07488923
STU20260523
Inclusion Criteria
* ≥18 years of age at the time of signing the ICF
* Have been previously treated with at least one line of systemic standard of care (SOC) anti-cancer therapy for their respective cancer indication. Participants with locally advanced disease who are eligible for curative resection will be excluded.
* Have documented radiological disease progression/relapse during or after their most recent line of anti-cancer therapy with measurable disease on imaging, as assessed by RECIST v1.1
* Have histologically and/or cytologically confirmed diagnosis of select advanced or metastatic R/R solid tumor malignancy in one of the following: R/R SCLC, R/R GEP-NEC, R/R high-grade NEPC, R/R epNEC with biopsy-documented DLL3 expression on archival tissue or fresh biopsy by local or central assessment. CNS NEC is excluded. Participants with mixed histologies for any of these indications qualify if the small cell/neuroendocrine tumor cell percentage is \> 50%, except for high-grade NEPC where neuroendocrine component must be \> 20%.
* Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0 or 1
* Life expectancy ≥12 weeks
* Have adequate hematologic and end-organ function
Exclusion Criteria:
* Previous systemic anti-cancer therapies within the timeframes, as specified in the protocol.
* Prior exposure/treatment with DLL3-targeted CAR T therapy or any other genetically engineered adoptive T cell therapy.
* Prior allogeneic organ transplant (including allogeneic bone marrow transplant).
* Major surgical procedure within 4 weeks of the first dose of any study drug administration or anticipated to be in need of a major surgical procedure during the course of study.
* Participants with toxicities (as a result of prior anti-cancer therapy) which have not recovered to baseline or CTCAE v5.0 \ BIOLOGICAL: ML261
Small Cell Lung Cancer (SCLC ), Extrapulmonary Neuroendocrine Carcinoma (EP-NEC), Gastroenteropancreatic NEC (GEP NEC), Neuroendocrine Prostate Cancer (NEPC), Lung/Thoracic, Other Endocrine System
Neuroendocrine carcinoma, DLL3, CAR T
UT Southwestern
A Study Comparing Siplizumab With Rabbit Anti-Thymocyte Globulin to Help the Body Accept a Kidney Transplant (MODERNIZE1)
The goal of this clinical trial is to learn if siplizumab can prevent rejection of a kidney transplant in adult participants with end stage kidney disease. The main questions it aims to answer are: How many adverse events do participants receiving two different doses of siplizumab have compared to rabbit anti-thymocyte globulin (rATG)? How many participants successfully keep their kidney transplant after receiving siplizumab or rATG? This will be calculated as those participants that did not: die; have their kidney fail to work properly (graft loss); their body rejects their transplant (tissue sample (biopsy)-proven acute rejection: BPAR); or who were lost to follow-up. How does the body respond to siplizumab after dosing at each of the 2 dose levels? How does siplizumab work in the body compared to rATG? Selected participants will be divided into 3 groups. In 2 of the groups, participants will be given siplizumab at one of the two study medicine doses. Participants in the third group will be given rATG. All participants will take the usual anti-rejection medicines given before, during, and after a kidney transplant. All participants will also be given medicines before the study drug to lower the risk of reactions, and medicines used to prevent or treat infections after the transplant. Participants will be asked to provide their medical history at the first visit at the study site where you will have your kidney transplant. At the first visit and other visits participants will be asked to provide their medication history, have a physical exam, check vital signs, have blood drawn for tests, and have non-invasive tests that record the electrical activity of your heart (ECG) and blood draws. Participants will be monitored for 12 months after transplant surgery.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sarah.Joseph@UTSouthwestern.edu
David Wojciechowski
ALL
18 Years to 70 Years old
PHASE2
NCT07508787
STU20260532
Inclusion Criteria:
* Recipients of a renal allograft from a non-HLA identical living or deceased donor.
* Recipients of a kidney with a cold ischemia time \< 30 hours; hypothermic machine perfusion within the same timeframe is acceptable.
* Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, must agree to use highly effective methods of contraception.
Exclusion Criteria:
* Transplant recipients seronegative for EBV.
* Transplant recipients receiving a kidney from a non-heart beating donor (ie, DCD) whose organ is retrieved from an uncontrolled DCD or whose donor age \> 55 years of age.
* Multi-organ transplant recipients (eg, kidney-pancreas, organ other than kidney), dual-kidney transplant recipients, recipients with more than one prior kidney transplant, or hematopoietic stem cell transplantation recipients.
* Presence of current or historical DSA via single-antigen bead assay or local SoC. The MFI cut-off value used to determine the presence of DSA will be defined as per the institutional SoC. Results within 3 months prior to transplant are acceptable.
* Crossmatch positive (isolated positive B cell crossmatches are not an exclusion criterion).
* ABO-incompatible recipient.
* Administration of complement inhibitor therapy within 6 months prior to the transplant, or likely to require treatment with complement inhibitor therapy during the study.
* Participants receiving immunosuppressive therapies prior to transplant for pre-existing conditions must be candidates for the protocol-defined regimen.
* History of malignancy of any organ system, except for localized excised non-melanomatous skin lesions or carcinoma in situ of the cervix.
* Seropositive for human immunodeficiency virus or hepatitis B surface antigen. Participants who are seropositive for hepatitis C virus (HCV) are excluded without proof of sustained viral response after anti-HCV treatment.
* Recipient of a kidney from a donor who tests positive for human immunodeficiency virus or hepatitis B surface antigen/hepatitis B core protein.
* History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (eg, siplizumab, rATG, TAC, MPA derivatives, CS).
* Evidence of active tuberculosis (TB) infection (participants with a history of latent TB may become eligible after treatment with anti-TB therapy according to national guidelines).
* Participants with severe systemic infection(s), at the time of screening or within 2 weeks prior to randomization DRUG: Siplizumab, DRUG: Rabbit anti-thymocyte globulin
Renal Transplant Failure and Rejection
UT Southwestern
Examining the Feasibility of Using Pressure Gradient Regulated Automated Cerebral Spinal Fluid Drainage During External Lumbar Drain Trials (UPGRADE)
The intellidrop device is an FDA-approved system that automates safe, small volume of cerebral spinal fluid drainage with continuous pressure monitoring, reducing nursing workload and human error while improving patient mobility and comfort
Call 214-648-5005
studyfinder@utsouthwestern.edu, Haben.Mehari@UTSouthwestern.edu
Padraig O'Suilleabhain
ALL
60 Years to 99 Years old
NA
NCT07494812
STU20260216
Inclusion Criteria:
* All patients will be adults aged 60 years or older with suspected iNPH who are being admitted to the hospital for the purpose of an LDT specifically to evaluate for benefit from shunt placement.
Exclusion Criteria:
* Patients who are under 18 years of age, pregnant, or are currently incarcerated will be excluded from participating in this study. DEVICE: Intellidrop Automated CSF Drainage System, DEVICE: Intellidrop Automated CSF Drainage System
NPH (Normal Pressure Hydrocephalus)
UPGRADE, Cerebrospinal fluid buildup (CSF buildup)
UT Southwestern
A Study of TORL-5-700 in Relapsed/Refractory Non Hodgkin's Lymphoma
A Phase 1/2 study to evaluate safety, tolerability, and anticancer activity of TORL-5-700 as a monotherapy and in combination in R/R NHL
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Praveen Ramakrishnan Geethakumari
ALL
18 Years to old
PHASE1
NCT07439653
STU20261050
Inclusion Criteria:
* Confirmed B-NHL, including but not limited to de novo DLBCL; FL, Grades 1 to 3A; MCL; transformed lymphoma (tFL, RT) and FL Grade 3B; MZL and MALT.
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
* At least 1 measurable lesion per Lugano criteria.
* Tumor tissue is available.
* Adequate organ function
Exclusion Criteria:
* T-cell lymphoma
* CLL or SL
* Burkitt lymphoma and high-grade B-cell lymphoma
* CNS involvement
* Peripheral neuropathy \> Grade 2
* Uncontrolled medical conditions
* Viral infections DRUG: TORL-5-700, DRUG: TORL-5-700 at MTD/RP2D, DRUG: TORL-5-700 at MTD/RP2D in combination with another agent
Histologically Confirmed Relapsed or Refractory B-cell Non-Hodgkin Lymphoma, Non-Hodgkins Lymphoma
UT Southwestern
A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer
Pancreatic cancer is difficult to diagnose early. By the time people have been diagnosed, the cancer has usually spread to other parts of the body (metastatic). The standard treatment is chemotherapy, but other treatments are needed to improve outcomes in people with pancreatic cancer. The first treatment that people usually receive is chemotherapy. At the time this study started, some of the main standard chemotherapies for pancreatic cancer were mFOLFIRINOX or NALIRIFOX. Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Many people with pancreatic cancer have a faulty KRAS gene. One such change in the KRAS gene is called a G12D mutation. Researchers are looking for ways to stop the actions of abnormal proteins made from the KRAS G12D mutation. This study is about setidegrasib given with chemotherapy in people with pancreatic cancer who have the KRAS G12D mutation. Before setidegrasib can become an approved treatment, clinical studies need to be completed to understand how it works and how safe it is. The main aim is to learn if people who are given setidegrasib with chemotherapy live for longer than people who are given placebo with chemotherapy. Other aims are to learn if setidegrasib delays the cancer and symptoms returning, how the body processes setidegrasib, and its safety, when given with chemotherapy. People in this study will be adults with metastatic pancreatic cancer with the G12D mutation in their KRAS gene. Surgery or radiotherapy will not be an option to cure their cancer. People cannot take part if the cancer cells have spread to the thin tissue covering the brain and spinal cord (leptomeningeal disease), have symptoms of cancer in the brain or nervous system, or have recently had some other cancers that required treatment. In this study, people are given either setidegrasib with mFOLFIRINOX or NALIRIFOX chemotherapy, or a placebo with mFOLFIRINOX or NALIRIFOX chemotherapy. Whether people receive setidegrasib or placebo is decided by chance. The study doctor decides which chemotherapy (mFOLFIRINOX or NALIRIFOX) people receive. People will only receive NALIRIFOX chemotherapy (with setidegrasib or placebo) after the safety of setidegrasib with NALIRIFOX chemotherapy has been confirmed in another ongoing setidegrasib study. All of the study treatments are given slowly through a tube into a vein (infusion). People will continue to receive study treatment until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly they pass away. There will be safety checks at each visit, and the doctors will continue to check for medical problems and people's wellbeing throughout the study.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years to old
PHASE3
NCT07409272
STU20260137
Inclusion Criteria:
* Participant has histologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) with documented Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutation based on local or central testing (confirmation of a participant's positive KRAS G12D mutation result must be available prior to randomization).
* Participant has no option for surgical resection or radiotherapy with curative intent.
* Participant consents to and provides a baseline tumor tissue specimen for the study during screening. The sample must meet the requirements described in the laboratory manual and the tumor sample guidance.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 within 7 days prior to randomization.
* Participant has adequate organ function as indicated by the following laboratory values within 7 days prior to randomization (if a participant has received a recent blood transfusion, the latest laboratory tests must be obtained ≥ 14 days after any blood transfusion). The laboratory values prior to the initiation of the first dose of setidegrasib/placebo (or mFOLFIRINOX/NALIRIFOX, if chemotherapy is administered during the screening period) should be used to determine eligibility. Participants who receive mFOLFIRINOX/NALIRIFOX during the screening period must meet these criteria within 7 days prior to the start of on-treatment chemotherapy (i.e., C1D1).
* Participant agrees not to participate in another interventional study while receiving study intervention in the present study (participant who is currently in the follow-up period of an interventional clinical trial is allowed).
Exclusion Criteria:
* Participant has neuroendocrine, acinar pancreatic carcinoma or pancreatic cancer with squamous/adenosquamous features.
* Participant has another prior malignancy active (i.e., requiring treatment, including hormonal therapies, or intervention) within the previous 2 years different from the primary malignancy for this study, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed.
* Participant has chronic inflammatory bowel disease, bowel obstruction and/or severe uncontrolled diarrhea.
* Participant has peripheral sensory neuropathy with functional impairment.
* Participant has ascites and/or pleural effusion that require invasive interventions within 30 days prior to randomization or have an indwelling drainage catheter.
* Participant has symptomatic pulmonary embolism or pulmonary embolism not being treated with anticoagulation.
* Participant has a history of interstitial lung disease or pulmonary fibrosis.
* Participant has uncontrolled seizure disorder or refractory to antiepileptics.
* Participant has known homozygous uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism.
* Participant has had a myocardial infarction, unstable angina or coronary artery bypass surgery within 6 months prior to randomization or currently has an uncontrolled illness including but not limited to symptomatic congestive heart failure, clinically significant cardiac disease (e.g., cardiomyopathy, infiltrative cardiac disease, etc.), unstable angina pectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker or long QT interval (QT) syndrome.
* Participant has received any prior systemic therapy for their metastatic PDAC (except with up to 2 doses \[i.e., 28 days; 1 cycle\] of mFOLFIRINOX or NALIRIFOX during the screening period. If a participant received \[neo\]adjuvant chemotherapy, tumor recurrence or disease progression must have occurred ≥ 6 months after completing the last dose of the \[neo\]adjuvant therapy).
* Participant has had prior treatment with a KRAS G12D-targeted agent.
* Participant has a corrected QT interval by Fridericia (QTcF) (single electrocardiogram \[ECG\]) \> 470 msec during the screening period. DRUG: Setidegrasib, DRUG: Oxaliplatin, DRUG: Leucovorin, DRUG: Irinotecan, DRUG: fluorouracil, DRUG: liposomal irinotecan, DRUG: Placebo
Pancreatic Cancer, Metastatic Pancreatic Cancer, Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Metastatic Pancreatic Cancer, Metastatic Pancreatic Adenocarcinoma, ASP3082, setidegrasib, KRAS G12D, PDAC, mFOLFIRINOX, NALIRIFOX
UT Southwestern
A Phase 1b Study of HC-7366, an Agonist of ISR With Immunotherapy in Kidney Cancer (SHARK)
To find out if the combination of HC-7366 and nivolumab (with or without ipilimumab) can help to control ccRCC. The
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years to old
PHASE1
NCT07401875
STU20252524
Eligibility Criteria
• Ability to understand and the willingness to sign a written informed consent document
• Male or female ≥ 18 years of age
• Confirmed diagnosis of clear cell RCC
• Stage IV metastatic RCC per American Joint Committee on Cancer
• Triplet Cohort (IO/IO): No prior systemic therapy for advanced RCC or prior adjuvant therapy allowed.
• Doublet Cohort: Participant must have progressed on at least one PD1 based doublet regimen (IO/IO or IO/TKI). Prior adjuvant therapy is allowed and does count as one line of systemic therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 )
• At least one measurable lesion as defined by RECIST 1.1 • A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion
• Has pathology-confirmed RCC. Extra tissue should be submitted if available for correlatives. Formalin-fixed paraffin-embedded tissue blocks are preferred to slides. Details pertaining to tumor tissue submission can be found in the Lab Procedures Manual.
• Willing and able to undergo bone and brain scans at baseline and continue to have scans performed if positive at screening.
• Adequate organ function within 28 days prior to first dose of protocol-indicated treatment, including: * White blood cell (WBC) ≥ 2,000 /μL * Absolute neutrophil count (ANC) ≥ 1,000/μL * Platelet count ≥ 100,000/μL * Hemoglobin (Hgb) ≥ 9.0 g/dL in prior 4 weeks. Blood transfusions are allowed to achieve this. * Serum creatinine ≤ upper limit of normal (ULN), or calculated creatinine clearance ≥ 30 mL/min (per the Cockcroft-Gault formula,) * Total bilirubin ≤ ULN (except subjects with Gilbert Syndrome, who must have total bilirubin \< 3.0 mg/dL) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
• Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment * "Women of childbearing potential" (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal * Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes * If menopausal status is considered for the purpose of evaluating childbearing potential, women \< 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential
• Women of childbearing potential (WOCBP) must agree to follow instructions for acceptable contraception prior to the study and from the time of signing consent, for the duration of the study participation and for 23 weeks after their last dose of protocol-indicated treatment * The effects of HC-7366 on the developing human fetus are unknown. For this reason and because first-in-class, first-in-human agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the study and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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 not azoospermic who are sexually active with WOCBP must agree to follow instructions for acceptable contraception prior to the study and from the time of signing consent, for the duration of the study participation, and for 31 weeks after their last dose of protocol-indicated treatment
• Participant s with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Participant s with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Participant s with previously treated brain metastases may be eligible provided they are radiologically (by MRI) and clinically stable (i.e., without evidence of disease progression) for at least 4 weeks (28 days) by repeat imaging (repeat imaging should be performed during study screening), with no evidence of new or enlarging brain metastases, and without requirement for steroid treatment for at least 28 days prior to the first dose of study drug or study therapy. (CT is acceptable if MRI is contraindicated)
• Participant s with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study
• Participant s 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 study, participant s should be class 2B or better Exclusion Criteria 1\. For the Triplet Cohort (Nivo/Ipi/HC-7366): * Prior systemic treatment including neoadjuvant or adjuvant therapy including an immune checkpoint inhibitor or TKI 2. For the Doublet Cohort (Nivo/HC-7366): * More than 3 prior lines of systemic therapy allowed * Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) ≤ 2 weeks before start of study drug or study therapy 3. ≤ 28 days before first dose of protocol-indicated treatment: * Major surgery requiring general anesthesia 4. ≤ 14 days before first dose of protocol-indicated treatment: * Radiosurgery or radiotherapy * Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery) * Active infection requiring systemic treatment 5. Known or suspected clinically significant active bleeding including active hemoptysis 6. Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug - e.g. Crohn's disease, ulcerative colitis, chronic diarrhea (defined as \> 4 loose stools per day), malabsorption, or bowel obstruction 7. Central nervous system (CNS) metastasis, unless asymptomatic and radiologically (by MRI) and clinically stable (i.e., without evidence of disease progression) for at least 4 weeks (28 days) by repeat imaging (repeat imaging should be performed during study screening), with no evidence of new or enlarging brain metastases, and without requirement for steroid treatment for at least 28 days prior to the first dose of study drug or study therapy. (CT is acceptable if MRI is contraindicated 8. Any condition requiring systemic treatment with either corticosteroids (\> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment * In the absence of active autoimmune disease: Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intraarticular, intranasal, and inhalational) ≤ 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids ≤ 10 mg/day prednisone or equivalent daily (e.g. hormone replacement therapy needed in participants with hypophysitis) 9. Active, known or suspected autoimmune disease * Subjects with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders such as vitiligo, psoriasis or alopecia not requiring systemic treatment; or conditions not expected by the investigator to recur in the absence of an external trigger are permitted to enroll 10. Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with and interpretation of scheduled visits, treatment schedule, laboratory tests and other study requirements 11. Pregnant women are excluded from this study because HC-7366 is novel, first-in-class small molecule agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with HC-7366, breastfeeding should be discontinued if the mother is treated with HC-7366. These potential risks may also apply to other agents used in this study 12. Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this study 13. Participants who are receiving any other investigational agents
• Ability to understand and the willingness to sign a written informed consent document
• Male or female ≥ 18 years of age
• Confirmed diagnosis of clear cell RCC
• Stage IV metastatic RCC per American Joint Committee on Cancer
• Triplet Cohort (IO/IO): No prior systemic therapy for advanced RCC or prior adjuvant therapy allowed.
• Doublet Cohort: Participant must have progressed on at least one PD1 based doublet regimen (IO/IO or IO/TKI). Prior adjuvant therapy is allowed and does count as one line of systemic therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 )
• At least one measurable lesion as defined by RECIST 1.1 • A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion
• Has pathology-confirmed RCC. Extra tissue should be submitted if available for correlatives. Formalin-fixed paraffin-embedded tissue blocks are preferred to slides. Details pertaining to tumor tissue submission can be found in the Lab Procedures Manual.
• Willing and able to undergo bone and brain scans at baseline and continue to have scans performed if positive at screening.
• Adequate organ function within 28 days prior to first dose of protocol-indicated treatment, including: * White blood cell (WBC) ≥ 2,000 /μL * Absolute neutrophil count (ANC) ≥ 1,000/μL * Platelet count ≥ 100,000/μL * Hemoglobin (Hgb) ≥ 9.0 g/dL in prior 4 weeks. Blood transfusions are allowed to achieve this. * Serum creatinine ≤ upper limit of normal (ULN), or calculated creatinine clearance ≥ 30 mL/min (per the Cockcroft-Gault formula,) * Total bilirubin ≤ ULN (except subjects with Gilbert Syndrome, who must have total bilirubin \< 3.0 mg/dL) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
• Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment * "Women of childbearing potential" (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal * Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes * If menopausal status is considered for the purpose of evaluating childbearing potential, women \< 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential
• Women of childbearing potential (WOCBP) must agree to follow instructions for acceptable contraception prior to the study and from the time of signing consent, for the duration of the study participation and for 23 weeks after their last dose of protocol-indicated treatment * The effects of HC-7366 on the developing human fetus are unknown. For this reason and because first-in-class, first-in-human agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the study and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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 not azoospermic who are sexually active with WOCBP must agree to follow instructions for acceptable contraception prior to the study and from the time of signing consent, for the duration of the study participation, and for 31 weeks after their last dose of protocol-indicated treatment
• Participant s with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Participant s with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Participant s with previously treated brain metastases may be eligible provided they are radiologically (by MRI) and clinically stable (i.e., without evidence of disease progression) for at least 4 weeks (28 days) by repeat imaging (repeat imaging should be performed during study screening), with no evidence of new or enlarging brain metastases, and without requirement for steroid treatment for at least 28 days prior to the first dose of study drug or study therapy. (CT is acceptable if MRI is contraindicated)
• Participant s with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study
• Participant s 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 study, participant s should be class 2B or better Exclusion Criteria 1\. For the Triplet Cohort (Nivo/Ipi/HC-7366): * Prior systemic treatment including neoadjuvant or adjuvant therapy including an immune checkpoint inhibitor or TKI 2. For the Doublet Cohort (Nivo/HC-7366): * More than 3 prior lines of systemic therapy allowed * Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) ≤ 2 weeks before start of study drug or study therapy 3. ≤ 28 days before first dose of protocol-indicated treatment: * Major surgery requiring general anesthesia 4. ≤ 14 days before first dose of protocol-indicated treatment: * Radiosurgery or radiotherapy * Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery) * Active infection requiring systemic treatment 5. Known or suspected clinically significant active bleeding including active hemoptysis 6. Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug - e.g. Crohn's disease, ulcerative colitis, chronic diarrhea (defined as \> 4 loose stools per day), malabsorption, or bowel obstruction 7. Central nervous system (CNS) metastasis, unless asymptomatic and radiologically (by MRI) and clinically stable (i.e., without evidence of disease progression) for at least 4 weeks (28 days) by repeat imaging (repeat imaging should be performed during study screening), with no evidence of new or enlarging brain metastases, and without requirement for steroid treatment for at least 28 days prior to the first dose of study drug or study therapy. (CT is acceptable if MRI is contraindicated 8. Any condition requiring systemic treatment with either corticosteroids (\> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment * In the absence of active autoimmune disease: Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intraarticular, intranasal, and inhalational) ≤ 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids ≤ 10 mg/day prednisone or equivalent daily (e.g. hormone replacement therapy needed in participants with hypophysitis) 9. Active, known or suspected autoimmune disease * Subjects with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders such as vitiligo, psoriasis or alopecia not requiring systemic treatment; or conditions not expected by the investigator to recur in the absence of an external trigger are permitted to enroll 10. Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with and interpretation of scheduled visits, treatment schedule, laboratory tests and other study requirements 11. Pregnant women are excluded from this study because HC-7366 is novel, first-in-class small molecule agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with HC-7366, breastfeeding should be discontinued if the mother is treated with HC-7366. These potential risks may also apply to other agents used in this study 12. Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this study 13. Participants who are receiving any other investigational agents
DRUG: Nivolumab, DRUG: HC-7366, DRUG: ipilimumab
Phase 1b, HC-7366, SHARK, Kidney Cancer, Kidney
UT Southwestern
A Study of Eloralintide (LY3841136) in Participants With Persistent Obesity Who Are Treated With a Weekly Incretin (ENLIGHTEN-6)
The main purpose of this study is to evaluate the efficacy and safety of eloralintide compared with placebo in participants with persistent obesity or overweight, with or without type 2 diabetes, and on stable incretin background therapy. Participation in the study will last about 80 weeks.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Elaine.Konda@UTSouthwestern.edu
Amy Shah
ALL
18 Years to old
PHASE3
NCT07392190
STU20252255
Inclusion Criteria:
* Are on stable incretin therapy at screening
* With persistent obesity or overweight defined as:
* ≥30 kg/m2 OR
* ≥27 kg/m2 with at least one existing obesity related complication at screening:
* hypertension
* dyslipidemia
* obstructive sleep apnea
* cardiovascular disease (for example, ischemic cardiovascular disease, New York Heart Association Functional Class I-III heart failure), or
* type 2 diabetes
* Have a stable body weight (\<5% body weight change) at screening
Exclusion Criteria:
* Have a prior or planned surgical treatment for obesity (liposuction, cryolipolysis, or abdominoplasty allowed if performed \>1 year before screening)
* Have a prior or planned endoscopic procedure and/or device-based therapy for obesity (prior device-based therapy acceptable if device removal was more than 6 months prior to screening)
* Have type 1 diabetes
* Have taken any of the following antihyperglycemic medications within 90 days before screening:
* dipeptidyl peptidase-4 (DPP-4) inhibitors
* amylin analogs
* insulin
* Have had within 90 days prior to screening:
* heart attack
* stroke
* coronary artery revascularization
* unstable angina, or
* hospitalization due to congestive heart failure
* Have a history or diagnosis of New York Heart Association Functional Classification Class IV congestive heart failure DRUG: Eloralintide, DRUG: Placebo
Overweight, Obesity
Amylin receptor agonist
UT Southwestern
Imaging Acetadote Metabolism in Glioblastoma
This goal of this clinical trial is to evaluate how Acetadote affects metabolism in patients with glioblastoma. Drugs like Acetadote, which affect the level of damage in a cell (oxidative stress), may impact brain tumor metabolism and slow the growth of brain tumors. The investigators are evaluating how Acetadote affects glioblastoma metabolism by using MRI-based methods and by determining the changes in metabolism in brain tumor tissue resected from patients with a new diagnosis of glioblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Evan Noch
ALL
18 Years to old
EARLY_PHASE1
NCT07387666
STU20250529
Inclusion Criteria:
* 1\. Glioblastoma
* 2\. Newly diagnosed with no prior surgery, radiation, chemotherapy, or other tumor-treating agent
* 3\. Age ≥18 years
* 4\. KPS \> 70
* 5\. Adequate organ and marrow function as defined below:
* \- Bilirubin ≤1.5 times upper limit of normal
* \- AST and ALT ≤ 3 times ULN
* \- Creatinine ≤ 1.5 x ULN and/or GFR ≤ 60 mL/min
* -ANC ≥ 1000 cells/ul
* \- Platelet ≥ 100,000/ul
* \- Hemoglobin ≥ 9 g/dl
* 6\. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* 6a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* \- Has not undergone a hysterectomy or bilateral oophorectomy; or
* \- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
* 7\. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
* 1.Chemotherapy, radiotherapy, or other cancer therapy within 4 weeks prior to starting study treatment.
* 2\. Subjects must have recovered from prior treatment-related toxicities to grade 2 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism from prior immune checkpoint inhibitor treatment).
* 3\. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
* 4\. Brain metastases
* 5\. History of allergic or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to Acetadote.
* 6\. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
* 7\. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. DRUG: Acetadote
Glioblastoma, GBM, Brain and Nervous System
UT Southwestern
IMPACT-MACS: Adrenalectomy vs Semaglutide for Metabolic Outcomes in Mild Autonomous Cortisol Secretion (IMPACT-MACS)
The goal of this study is to learn how two treatments-adrenalectomy (surgical removal of an adrenal gland) and semaglutide (a medication used for weight management)-affect insulin resistance and cortisol regulation in adults with mild autonomous cortisol secretion (MACS). The study will also learn how these treatments impact body composition, blood pressure, cholesterol, inflammation, muscle strength, and quality of life. The main questions the study aims to answer are: 1. Does adrenalectomy or semaglutide improve insulin resistance more in people with MACS? 2. How do these treatments change cortisol patterns and other cardiometabolic risk factors? 3. Do people with MACS respond differently to semaglutide compared to matched adults without MACS? Participants will: 1. Receive either adrenalectomy or semaglutide if they have MACS, or semaglutide if they are matched controls 2. Complete clinic visits and phone visits over about 26-30 weeks 3. Undergo metabolic testing such as blood tests, urine steroid profiling, body composition scans, blood pressure monitoring, muscle strength testing, and questionnaires about health and well-being
Call 214-648-5005
studyfinder@utsouthwestern.edu, MartinTzeWah.Kueh@UTSouthwestern.edu
Oksana Hamidi
ALL
18 Years to old
NA
NCT07361874
STU20251717
Inclusion Criteria:
* Adults ≥18 years
* MACS groups: adrenal adenoma + DST cortisol \>1.8 µg/dL + no overt Cushing + eligible for adrenalectomy
* Willingness to postpone surgery 6 months if randomized
* Controls: no adrenal abnormalities + normal DST + BMI ≥27 + ≥2 cardiometabolic conditions
* Stable medication doses for ≥4 weeks
* Negative pregnancy test if applicable
Exclusion Criteria:
* Prior GLP-1 RA within 90 days
* Weight change \>5 kg in past 90 days
* Prior obesity/diabetes surgery
* Type 1 diabetes or other diabetes types
* Severe organ disease
* Recent pancreatitis
* Pregnancy, breastfeeding
* Contraindication to semaglutide
* Contraindication to surgery delay
* Chronic glucocorticoid use PROCEDURE: Intervention 1: Adrenalectomy, DRUG: Intervention 2: Semaglutide
Mild Autonomous Cortisol Secretion (MACS), Autonomous Cortisol Secretion (ACS), Subclinical Cushing's, Mild Autonomous Cortisol Excess
Mild Autonomous Cortisol Secretion, MACS, Adrenal incidentaloma, Adrenal adenoma, Subclinical Cushing, Hypercortisolism, Cortisol dysregulation, Adrenalectomy, Semaglutide, Weight loss, Body composition, Insulin resistance, GLP-1 receptor agonist, Hyperinsulinemic-euglycemic clamp, Cortisol dynamics, Visceral fat, cardiometabolic risk, randomized controlled trial
UT Southwestern
A Study of CX11 Tablets in Patients With Type 2 Diabetes Mellitus
This study is testing whether a new medication called CX11 works and is safe for participants with type 2 diabetes who have not reached good blood sugar control while taking a steady dose of metformin, with or without a steady dose of an SGLT2 inhibitor, for at least 90 days. The study is being done at multiple medical centers. Participants are assigned by chance (randomized) to different groups, and neither the participants nor the study staff know which group they're in (double-blind). The groups are compared side by side (parallel), and some participants will receive inactive pills (placebo) to help measure the true effect of the study drug. After screening, participants will be randomly placed into one of six groups, with equal chances of being in any group. Each group will receive a different dose of CX11 or a placebo. Treatment will last 24 weeks. After that, all participants will have a 2-week follow-up period to check on safety.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Emily.Zhang@UTSouthwestern.edu
Emily Zhang
ALL
18 Years to 75 Years old
PHASE2
NCT07340320
STU20252558
Inclusion Criteria
Participants who meet all of the following criteria will be eligible to participate in this study:
* Adults aged 18 to 75.
* Diagnosis of type 2 diabetes for at least 6 months.
* HbA1c between 7.0% and 10.5%.
* Body mass index (BMI) between 23 and 50 kg/m².
* Body weight stable for the past 3 months before joining.
* Stable dose of metformin (≥1000 mg/day), with or without SGLT2i, for ≥3 months.
* Women of childbearing potential (WOCBP): highly effective contraception ≥6 months prior to screening, throughout study, and 90 days post-last dose; negative pregnancy test within 24 hrs of first dose; no intent to donate sperm/ova
* Agrees to avoid grapefruit/grapefruit products
Exclusion Criteria
Participants who meet any of the following criteria will be excluded from this study:
* Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or systemic corticosteroids).
* Type 1 diabetes or a history of diabetic ketoacidosis.
* Use of any GLP-1 receptor agonist within the past 6 months, or any prior exposure to CX11.
* Use of insulin to control blood sugar within the past 12 months.
* More than one episode of severe low blood sugar, with awareness of hypoglycemia symptoms.
* Cardiovascular or cerebrovascular conditions within the past 6 months:
* Heart attack, coronary angioplasty, or bypass surgery (diagnostic angiography allowed).
* Valvular heart disease or prior heart valve repair surgery.
* Unstable angina.
* Transient ischemic attack (TIA) or stroke.
* Decompensated heart failure (NYHA Class III or IV).
* ECG abnormalities indicating significant safety risk, such as supraventricular tachycardia, torsades de pointes, second- or third-degree AV block, myocardial infarction, QTcF \> 450 ms in males or \> 470 ms in females, PR interval \> 220 ms.
* Poorly controlled hypertension at screening: systolic ≥ 180 mmHg or diastolic ≥ 100 mmHg.
* Pancreatic or gallbladder conditions:
* Acute or chronic pancreatitis.
* Symptomatic gallbladder disease (previous cholecystectomy is allowed).
* Pancreatic injury or risk factors that increase pancreatitis risk.
* Thyroid conditions:
* Poorly controlled abnormal thyroid function on a stable dose before screening.
* Clinically significant abnormal thyroid test results at screening.
* Personal or first-degree family history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) type 2A or 2B.
* Cancer history:
* Malignancy within the past 5 years, regardless of recurrence or metastasis. Exceptions: localized basal cell skin cancer, low-risk prostate cancer, cervical carcinoma in situ, or high-grade prostatic intraepithelial neoplasia.
* Gastrointestinal conditions or treatments that may affect drug absorption:
* Abnormal gastric emptying (e.g., gastric outlet obstruction).
* Severe chronic gastrointestinal disease, including active ulcer within 6 months.
* Crohn's disease, ulcerative colitis, or other inflammatory bowel diseases.
* Prior gastrointestinal surgery (except polypectomy and appendectomy).
* Long-term use of drugs that directly affect gastrointestinal motility (e.g., mosapride, cisapride).
* Liver disease:
* Active liver disease other than nonalcoholic fatty liver.
* Chronic active hepatitis B or C.
* Primary biliary cirrhosis.
* Eye disease:
* Uncontrolled or potentially unstable diabetic retinopathy or maculopathy.
* Abnormal lab results at screening:
* eGFR \< 60 mL/min/1.73 m² (CKD-EPI).
* ALT or AST \> 2.5 × upper limit of normal (ULN).
* Total bilirubin \> 1.5 × ULN (except known Gilbert's syndrome).
* Serum amylase or lipase \> 1.5 × ULN.
* Fasting triglycerides \> 5.7 mmol/L.
* TSH \> 1.5 × ULN or \< 1.0 × LLN.
* Calcitonin ≥ 20 ng/L.
* Hemoglobin \< 110 g/L (male) or \< 100 g/L (female).
DRUG: CX11, OTHER: Placebo
Type II Diabetes Mellitus
Type 2 Diabetes Mellitus, HbA1C, Percentage change in HbA1C, Change in Fasting Plasma Glucose, Change in body weight, Body weight loss, Hypoglycemics episodes, Hypoglycemia, Continuous Glucose Monitoring, Blood glucose, Health Survey Short Form-36, Diabetes treatment satisfaction questionnaire, Columbia-suicide severity rating scale
UT Southwestern
A Study of Eloralintide (LY3841136) in Participants With Obesity, or Overweight Without Type 2 Diabetes (ENLIGHTEN-1)
The purpose of this study is to evaluate the efficacy and safety of eloralintide in adults with obesity or overweight who do not have type 2 diabetes. The study has two phases: a main phase and an extension phase. Participation in the main phase of the study will last about 75 weeks. Participants with prediabetes will continue in the extension phase for another 2 years.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Lina.GonzalezDuarte@UTSouthwestern.edu
Amy Shah
ALL
18 Years to old
PHASE3
NCT07321886
STU20252251
Inclusion Criteria:
* Have Body Mass Index (BMI) at screening of the following:
* 30 kilogram per square meter (kg/m2) OR
* 27 kg/m2 with at least one of the following weight-related health conditions at screening:
* high blood pressure
* dyslipidemia
* obstructive sleep apnea, or
* heart disease
* Have a stable body weight (\<5% body weight change) for 90 days prior to screening.
* Have a history of at least one self-reported unsuccessful dietary effort to reduce body weight
Exclusion Criteria:
* Have a prior or planned surgical treatment for obesity (liposuction, cryolipolysis, or abdominoplasty allowed if performed \>1 year before screening)
* Have a prior or planned endoscopic procedure and/or device-based therapy for obesity (prior device-based therapy acceptable if device removal was more than 6 months prior to screening)
* Have type 1 diabetes or type 2 diabetes
* Have had within 90 days prior to screening:
* heart attack
* stroke
* coronary artery revascularization
* unstable angina, or
* hospitalization due to congestive heart failure
* Have a history or diagnosis of New York Heart Association Functional Classification Class IV congestive heart failure
* Have taken medications or alternative remedies intended for weight loss within 90 days of screening DRUG: Eloralintide, DRUG: Placebo
Obesity, Overweight
UT Southwestern
Phase II Trial of PSA Response-based Androgen Deprivation Therapy and Nodal Coverage for Prostate Cancer Early Salvage Radiotherapy (RANGER) ((RANGER))
This Phase II, single arm study evaluates a PSA-response-adapted approach to salvage radiotherapy after radical prostatectomy for prostate cancer. All participants will receive hypo-fractionated stereotactic radiotherapy to the prostate fossa. At 5 weeks, biochemical response will be assessed. responders will proceed to observation, while non responders will receive sequential pelvic nodal radiotherapy and 4 months of androgen deprivation therapy (ADT). The study aims to determine whether this response base approach achieves non inferior 2 year freedom from progression compared with historical outcomes using routine pelvic nodal radiotherapy and ADT in all patients.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aurelie Garant
MALE
18 Years to old
PHASE2
NCT07313241
STU20251220
Inclusion Criteria:
* Men aged ≥18 years with histologically confirmed prostate adenocarcinoma treated with prostatectomy in the localized setting within 10 years, with post-operative PSA (persistent or rising) of ≥0.05ng/mL.
* Radical prostatectomy ≥4 months prior to enrollment without nodal involvement (pN0 or pNx)
* Performance status ECOG 0-2
* No definite evidence of regional or distant metastatic disease by at least pelvic imaging within 90 days of registration. Equivocal findings are allowed at investigator discretion. Imaging is specified as follows:
* PSA\>=0.2ng/mL: positron emission tomography (PET) with FDA-approved advanced imaging agent for prostate cancer (e.g. PSMA) required.
* PSA \<0.2 n/gm: PET with above noted agents OR conventional CT or MRI at investigator discretion.
* All sexually active men must agree to use adequate contraception for the duration of study therapies and a period of 60 days thereafter. Should a female partner of a trial participant become pregnant or suspect she is pregnant while the subject is participating in this study, the patient should inform his treating physician immediately.
* Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
* Prior androgen deprivation therapy (ADT) \> 3 months OR anti-androgen therapy (AAT) of \> 30 days. For shorter courses of either, at least 30 day "wash out" period is required with confirmation of resolved castration of testosterone to \>50ng/mL.
* Ongoing testosterone replacement therapy (TRT) with refusal to discontinue (must be stopped with demonstration of detectable PSA ≥0.05ng/mL and non-castrate testosterone \>50ng/mL after 14 days of TRT cessation)
* Prior pelvic radiotherapy
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
* History of bladder neck or urethral stricture requiring procedural intervention.
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to actively interfere with the safety or efficacy assessments of this study in the investigator's view.
* Active inflammatory bowel disease requiring recurring systemic or steroid/enema therapy RADIATION: Prostate Fossa Radiotherapy, RADIATION: Pelvic nodal Radiotherapy, DRUG: Androgen Deprivation Therapy (ADT)
Prostate Cancer, Prostate
UT Southwestern; Parkland Health & Hospital System
A Study to Assess Adverse Events and How Intravenous (IV) Pivekimab Sunirine Moves Through the Body in Pediatric Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is an aggressive blood cancer, withwith few options for participants who relapse after treatment or who don't respond to treatment. This study will assess the adverse events and how pivekimab sunirine moves through the body in pediatric participants with relapsed or refractory (R/R) AML. Pivekimab sunirine is a drug being evaluated in the treatment of AML. This is an open label, single arm study, participants will be enrolled in 1 of the 3 cohorts based on their age and will receive pivekimab sunirine at a dose based on their weight. Around 18 pediatric participants with a diagnosis of AML will be enrolled in the study at approximately 30 sites around the world. Participants will receive intravenous (IV) pivekimab sunirine alone. The total study duration is approximately 28 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Caroline Smith
ALL
6 Months to 17 Years old
PHASE1
NCT07306832
STU20260749
Inclusion Criteria:
* Must have histologically confirmed acute myeloid leukemia (AML) meeting one of the following disease criteria:
* Second or greater relapse. OR
* Disease refractory to second or subsequent line of therapy (defined as resistant disease after at least one cycle of each treatment regimen).
* Must have myeloid leukemic blasts that are CD123-positive by flow cytometry as determined by the treating institution.
* Has \>= 5% myeloid leukemic blasts in bone marrow at time of relapse or refractory disease and prior to Screening for this study.
* Performance status by Lansky (\< 16 years old at evaluation) or Karnofsky (\>= 16 years old at evaluation) score \>= 50 or ECOG score \<= 2.
* May have status of central nervous system (CNS)1, CNS2, or CNS3 disease without clinical signs or neurologic symptoms suggestive of CNS leukemia, such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome. Participants receiving intrathecal therapy and no additional CNS-directed systemic therapy at study entry are eligible and may continue treatment as clinically indicated in accordance with institutional practice.
* For those participants who have not reached the age of consent, parent or legal guardian with the willingness and ability to provide informed consent and participant willing and able to give assent, as appropriate for age and country.
Exclusion Criteria:
* Known clinically significant cardiac disease.
* Down syndrome.
* Acute promyelocytic leukemia (APL) or juvenile myelomonocytic leukemia (JMML).
* Symptomatic central nervous system (CNS3) disease
* Prior history of any severity veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) of the liver.
* Prior history of hematopoietic stem cell transplant within 6 months prior to Screening without evidence of active GvHD at the time of screening and the participant is off medications to treat or prevent either post-transplant graft-versus-host disease (GvHD) or post-transplant rejection (except for a stable dose of corticosteroids).
* Have received prior Chimeric Antigen Receptor T-cell (CAR-T) therapy.
* Any other known current malignancy requiring therapy.
* Currently receiving anticancer therapy with antineoplastic intent, including radiotherapy, systemic therapy small molecules, monoclonal antibodies, other investigational agents, or high-dose chemotherapy with the exception of intrathecal therapy. DRUG: Pivekimab Sunirine
Acute Myeloid Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
Acute Myeloid Leukemia, Relapsed, Refractory, Pivekimab Sunirine, PVEK, Pediatric
Children’s Health
A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B (ATLAS-KIDS)
This is a parallel, Phase 3, two-arm, open-label study to evaluate the efficacy and safety of treatment with fitusiran prophylaxis administered to male pediatric participants (aged 1 to \<12 years) who have severe hemophilia A or B, with or without inhibitory antibodies to FVIII or FIX. Number of participants: Approximately 85 participants will be enrolled into the study: * Approximately 60 fitusiran-naïve participants with severe hemophilia A or B, with or without inhibitors (fitusiran-naïve arm), and * Approximately 25 participants with severe hemophilia A or B with inhibitors rolling over from the EFC15467\* dose confirmation study (roll-over arm). * Fitusiran has been investigated in the pediatric population in study EFC15467, which enrolled male participants aged 1 to \<12 years with hemophilia A or B with inhibitors to examine the safety and tolerability of fitusiran in the pediatric population. Participants will be enrolled into 1 of 2 arms: * Fitusiran-naïve: these participants have not previously received fitusiran, and they will undergo screening and study eligibility assessments. Once enrolled, they will go through a 24-week standard of care (SOC) period before starting fitusiran prophylaxis. * Roll-over participants from the EFC15467 study: only participants who are still on active treatment in study EFC15467 and consenting to study EFC17905 will be eligible to roll over. They will not need to undergo screening or further eligibility assessments. They will directly enroll into the fitusiran treatment period and continue treatment on their current fitusiran dose. The duration of fitusiran treatment will be up to 160 weeks for the fitusiran-naïve arm and up to 60 weeks for the roll-over arm.
Call 214-648-5005
studyfinder@utsouthwestern.edu, susan.corley@childrens.com
Jessica Garcia
MALE
1 Year to 11 Years old
PHASE3
NCT07285460
STU20252266
Inclusion Criteria:
Participants not previously exposed to fitusiran are eligible to be included in the study only if all of the following criteria apply:
* Participant must be 1 to \<12 years of age at the time of enrollment.
* Participants must have severe hemophilia A or B (FVIII \<1% or FIX ≤2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
* Participants must meet inhibitor or non-inhibitor status as defined below:
Inhibitor:
Requiring use of BPA for prophylaxis or BPA as on-demand therapy for any bleeding episodes for at least the last 3 months prior to screening, and meet one of the following Nijmegen-modified Bethesda assay results criteria:
* Inhibitor titer of ≥0.6 BU/mL at screening, OR
* Inhibitor titer of \<0.6 BU/mL at screening with medical record evidence of 2 consecutive titers ≥0.6 BU/mL, OR
* Inhibitor titer of \<0.6 BU/mL at screening with medical record evidence of 1 inhibitor titer ≥0.6 BU/mL and a history of anamnestic response, or severe allergic reaction (eg, anaphylaxis) or nephrotic syndrome
Non-inhibitor:
Requiring use of clotting factor concentrates (CFCs) for prophylaxis or CFCs as on-demand therapy for any bleeding episodes for at least the last 3 months prior to screening, and meet each of the following criterion:
* Nijmegen-modified Bethesda assay inhibitor titer of \<0.6 BU/mL at screening, AND
* No use of BPA to treat bleeding episodes for at least the last 3 months prior to screening
* Participants must have adequate peripheral venous access, as determined by the Investigator, to allow the blood draws required by the study protocol.
* Male: There are no contraceptive requirements for this study except where required by local regulations.
* Capable of giving signed informed consent/assent. A signed written informed consent must be obtained from parent(s)/legal guardian (hereafter referred to as the "parent"), as well as a written or oral assent obtained from participant, per local and national requirements.
Exclusion Criteria:
Participants not previously exposed to fitusiran are excluded from the study if any of the following criteria apply:
* Known co-existing bleeding disorders other than hemophilia A or B.
* Presence of clinically significant liver disease.
* History of antiphospholipid antibody syndrome.
* History of arterial or venous thromboembolism, unrelated to an indwelling venous access
* Any condition (eg, medical concern), which in the opinion of the Investigator, would make the participant unsuitable for dosing or which could interfere with the study compliance, the participant's safety and/or the participant's participation in the completion of the treatment period of the study.
* History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
* Subjects with a central or peripheral indwelling catheter, with a history of venous access complications (such as infections, thrombosis) leading to hospitalization and/or systemic anticoagulation therapy in the last 12 months.
* At screening, anticipated need of surgery during the study or planned surgery scheduled to occur during the study.
* Completion of a surgical procedure within 14 days prior to screening, or currently receiving additional BPA infusion for postoperative hemostasis.
* History of intolerance to SC injection(s).
* Current participation in ITI therapy.
* The use of emicizumab (Hemlibra®) or any non-factor bleed management treatment within 6 months prior to screening
* Prior gene therapy
* Current or future participation in another clinical study, scheduled to occur during this study, involving an investigational product other than fitusiran or an investigational device.
* AT activity \<60% at screening, as determined by central laboratory analysis.
* Co-existing thrombophilic disorder.
* Presence of an active Hepatitis C virus infection
* Presence of acute hepatitis A or Hepatitis E virus infection.
* Presence of acute or chronic hepatitis B virus infection.
* Platelet count ≤100 000/μL.
* Presence of acute infection at screening.
* Human immunodeficiency virus (HIV) positive with a CD4 count of \<400 cells/μL.
* Estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (using the Schwartz formula).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. DRUG: Fitusiran, BIOLOGICAL: Clotting factor concentrates (CFC) or bypassing agents (BPA), BIOLOGICAL: Antithrombin concentrate (ATIIIC)
Hemophilia
Children’s Health
DOC1021 Dendritic Cell Immunotherapy for Refractory Melanoma
The goal of this clinical trial is to learn if DOC1021 + pIFN will be safe and will lead to tumor responses in patients with refractory melanoma. DOC1021 is a dendritic cell immunotherapy derived from a patient's own blood cells and loaded with antigens from the patient's tumor in the form of tumor lysate and mRNA. The goal is to stimulate a T cell immune response that eliminates tumor cells. The study consists of two components: an initial phase I safety study to confirm safety/tolerability of the treatment regimen, and, subsequently, a single-arm phase II cohort to assess efficacy of the treatment regimen. All participants will: * Take filgrastim subcutaneously x 5 doses and subsequently undergo a leukapheresis collection * Receive two doses of DOC1021 under image guidance 2 weeks apart * Receive subcutaneous pIFN injections weekly for a total of 4 doses in parallel with the DOC1021 injections * Undergo an optional image-guided perinodal DOC1021 booster injection approximately 6 months after the first DOC1021 dose along with additional subcutaneous pIFN injections at time of the booster and the subsequent week for a total of 2 pIFN doses * Visit the clinic regularly to assess quality of life, symptoms, medication use, imaging, bloodwork, and to receive optional treatment with anti-PD1 agents
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sanjay Chandrasekaran
ALL
18 Years to old
PHASE1
NCT07288112
STU20260277
Inclusion Criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and avail-ability for the duration of the study
• Age 18 years or older
• Patients diagnosed with unresectable or metastatic melanoma and progressed following ≥1 prior systemic therapy including anti-PD-1 (i.e., refractory to anti-PD-1). Refractory defined as primary or secondary resistance as per SITC guidelines, except that confirmatory scan not required if clinical progression requiring surgery or radiation to relieve symptoms
• Willing and able to withhold anti-PD-1 treatment from the time of enrollment through \~6 weeks after the first DOC1021 administration
• One or more lesions available for biopsy or resection to yield at least 50 mg (e.g., 5 core biopsies) and preferably 100 mg of tumor for generating DOC1021 and at least 1 measurable target tumor lesion evaluable after DOC1021 by RECIST version 1.1.
• Brain metastases allowed if stable after prior treatment
• Ability to receive filgrastim (e.g. Neupogen), leukapheresis and perinodal injections of DOC1021 near regional nodes + weekly pIFN x 4 weeks.
• Females of reproductive potential must have a negative serum pregnancy test and agree to use effective contraception (as deter-mined appropriate for the patient by the investigator) during study treatment.
• Adequate kidney, liver, bone marrow function, and immune function, as follows:
• Hemoglobin ≥ 8.0 gm/dL (use of transfusion or other intervention to achieve is acceptable)
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Platelet count ≥ 75,000/mm3
• Calculated creatinine clearance (CrCl) \> 30 mL/min using Cockcroft and Gault formula: i. For males = (140 - age\[years\]) x (body weight \[kg\]) / (72 x serum creatinine \[mg/dL\]) ii. For females = 0.85 x value from male formula e. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) except in patients with Gilbert's disease for which total bilirubin must be ≤ 3 times ULN f. Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) ≤ 3 times the ULN (or ≤ 5.0 × ULN if liver metastases)
• Eastern Cooperative Group (ECOG) Performance Score 0 or 1
Exclusion Criteria:
• Patients who are pregnant or breastfeeding.
• Known active HIV or hepatitis infection. Patients with HIV that is well-controlled and have undetectable viral titers remain eligible. Patients with history of HCV adequately treated such that RNA viral load is negative also remain eligible.
• Any severe or uncontrolled medical condition or other condition that could affect participation in this study as determined by the investigator, including but not limited to uncontrolled or severe cardiac dis-ease, systemic autoimmune disorders requiring immunosuppression\*, autoimmune hyper/hypothyroidism, untreated viral hepatitis, autoimmune hepatitis (\*autoimmune disorders include but are not limited to rheumatoid arthritis, psoriasis and inflammatory bowel disease and immunosuppressive medications include DMARDs like methotrexate, TNF inhibitors, IL-6 receptor blockers, CD80/86 inhibitors, anti-CD20 and JAK inhibitors)
• Residual immune-related toxicities from prior immunotherapy \> Grade 1 severity. However, patients who experienced prior endocrine toxicity are eligible if well-controlled on replacement therapy.
• Treatment with another investigational drug or other experimental intervention within the last 30 days.
BIOLOGICAL: DOC1021, PROCEDURE: Tumor resection, DRUG: pIFN (peginterferon alfa-2a)
Refractory Melanoma, Melanoma, skin
Dendritic Cell Vaccine, Immunotherapy, Tumor Vaccine
UT Southwestern
A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck Cancer (OrigAMI-5)
The purpose of this study is to compare anti-tumor activity of amivantamab in addition to pembrolizumab and carboplatin versus pembrolizumab, 5-fluorouracil (FU), and platinum therapy (carboplatin or cisplatin) in participants with refractory/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). HNSCC is a type of cancer that develops in the head and neck regions, including the outer tissue layer of the mouth and throat. This study will focus on participants with HNSCC who are treatment-naive (have not received prior treatment) in the R/M setting.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yu Cao
ALL
18 Years to old
PHASE3
NCT07276399
STU20260092
Inclusion criteria:
* Be more than or equal to (\>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater)
* Have histologically or cytologically confirmed recurrent/metastatic (R/M) HNSCC that is considered incurable by local therapies: a. eligible primary tumor locations are the oral cavity, oropharynx, hypopharynx, or larynx; b. Must not have a primary tumor site of nasopharynx or primary tumor of unknown location; c. Must have documented local testing results per local regulations; d. Human papillomavirus (HPV) status must be known for participants with primary tumor location in oropharynx via p16 test, HPV DNA test, or high-risk HPV in situ hybridization (ISH). Any known p16, HPV DNA, or high-risk HPV ISH status of tumor must be negative
* Be treatment-naive for systemic therapy in the R/M setting
* Have an ECOG performance status of 0 or 1
* Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1
Exclusion criteria:
* Have an uncontrolled illness
* Have untreated brain metastases or history of known presence of leptomeningeal disease
* Have a history of clinically significant cardiovascular disease
* Inadequate organ or bone marrow function
* Known allergies, hypersensitivity, contraindications, or intolerance to excipients of: Amivantamab, Pembrolizumab, Carboplatin, Cisplatin, 5-FU and Hyaluronidase
BIOLOGICAL: Amivantamab, BIOLOGICAL: Pembrolizumab, DRUG: Carboplatin, DRUG: 5-Flurouracil, DRUG: Cisplatin
Squamous Cell Carcinoma of Head and Neck, Larynx, Lip, Oral Cavity and Pharynx
UT Southwestern
A Study Comparing JNJ-79635322 and an Anti-B-cell Maturation Antigen (BCMA)xCD3 Bispecific Antibody in Participants With Relapsed or Refractory Multiple Myeloma (TRIlogy-4)
The purpose of this study is to evaluate how well JNJ-79635322 works when compared with an anti-B-cell maturation antigen (BCMA)xCD3 bispecific antibody.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
ALL
18 Years to old
PHASE3
NCT07258511
STU20260692
Inclusion:
* Documented diagnosis of multiple myeloma (MM) as defined by the criteria below:
• MM diagnosis according to the international myeloma working group (IMWG) diagnostic criteria
• Measurable disease at screening as assessed by central laboratory * Received at least 3 prior lines of antimyeloma therapy including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-cluster of differentiation (CD)38 antibody * Documented evidence of progressive disease (PD) or failure to achieve a response to the last line of therapy based on investigator's determination of response by IMWG criteria * Toxicity related to previous anticancer therapy must have resolved to Grade 1 or better * Have an eastern cooperative oncology group (ECOG) performance status of 0 to 2 at screening and immediately before the start of study treatment administration Exclusion: * Active hepatitis of infectious origin * Known active or prior central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM * Suspected or known allergies, hypersensitivity, or intolerance to the excipients of JNJ-79635322 and Teclistamab * Major surgery, (example, requiring general anesthesia) within 2 weeks before first dose, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study * Received or plans to receive any live, attenuated vaccine within 4 weeks before the first dose of study treatment, or during study treatment
• MM diagnosis according to the international myeloma working group (IMWG) diagnostic criteria
• Measurable disease at screening as assessed by central laboratory * Received at least 3 prior lines of antimyeloma therapy including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-cluster of differentiation (CD)38 antibody * Documented evidence of progressive disease (PD) or failure to achieve a response to the last line of therapy based on investigator's determination of response by IMWG criteria * Toxicity related to previous anticancer therapy must have resolved to Grade 1 or better * Have an eastern cooperative oncology group (ECOG) performance status of 0 to 2 at screening and immediately before the start of study treatment administration Exclusion: * Active hepatitis of infectious origin * Known active or prior central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM * Suspected or known allergies, hypersensitivity, or intolerance to the excipients of JNJ-79635322 and Teclistamab * Major surgery, (example, requiring general anesthesia) within 2 weeks before first dose, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study * Received or plans to receive any live, attenuated vaccine within 4 weeks before the first dose of study treatment, or during study treatment
DRUG: JNJ-79635322, DRUG: Teclistamab
Multiple Myeloma
UT Southwestern
Phase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma (SURF303)
A Phase 2A/B study of Dabogratinib (TYRA-300) in Low Grade Upper Tract Urothelial Carcinoma
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
ALL
18 Years to old
PHASE2
NCT07265947
STU20260411
• Participants ≥ 18 years of age at the time of informed consent and willing and able to comply with all required study procedures
• Confirmed LOW RISK LG UTUC (both favorable and unfavorable) per AUA
• At least 5mm of marker lesion left behind
• Participants must have previous genomic report or archival/fresh tissue in addition to urine sample for retrospective genomic testing
• Identification of marker lesion(s) within 8 weeks prior to randomization (refer to Inclusion Criterion #2)
• If synchronous NMIBC, NMIBC must be fully resected and low-grade Ta or T1
• No prior BCG administration within 1 year of date of consent.
• No intravesical chemotherapy within 8 weeks prior to C1D1 (including UGN-101).
• No systemic chemotherapy within 3 months prior to C1D1
• ECOG 0-2
• Pathology consists of pure urothelial carcinoma
• Adequate bone marrow, liver, and renal function:
• i. Absolute neutrophil count (ANC) ≥1,500/mm3 ii. Platelet count ≥75,000/mm3 iii. Hemoglobin ≥10.0 g/dL
• i. Total bilirubin ≤ ULN ii. Alanine aminotransferase (ALT) ≤ ULN iii. Aspartate aminotransferase (AST) ≤ ULN
• Estimated glomerular filtration rate \>60 mL/min
• Serum Phosphate level ≤ ULN prior to starting treatment
• International normalized ratio (INR) ≤1.5 × ULN
Exclusion Criteria:
• Evidence or any features of high grade (HG) UTUC
• History of carcinoma in situ (CIS)
• History of prostatic urethral involvement
• Current or previous history of muscle invasive bladder cancer
• Current or previous history of lymph node positive and/or metastatic bladder cancer
• Evidence of squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma or small cell of the bladder
• Currently receiving systemic cancer therapy (cytotoxic or immunotherapy)
• Current or prior history of pelvic external beam radiotherapy for bladder cancer
• Current or history of receiving a prior FGFR inhibitor
• Systemic immunotherapy within 6 months prior to randomization
• Treatment with an investigational agent within 30 days or 5 half-lives from randomization, whichever is shorter; compounds with an unknown half-life will be default to 30 days.
• Prior treatment with an intravesical or intracavitary agent within 8 weeks of C1D1.
• Current evidence of central serous retinopathy or retinal pigmented epithelial detachment of any grade at time of baseline examination.
• Requiring use of medications that are potential inhibitors or inducers of CYP3A (prohibited list of medications)
DRUG: Dabogratinib (TYRA-300) 60mg, DRUG: Dabogratinib (TYRA-300) 80mg, DRUG: Dabogratinib (TYRA-300) TBD
Low Grade Upper Tract Urothelial Carcinoma, Urinary Bladder
Low-grade UTUC, Upper Tract Urothelial Carcinoma, Low Grade Upper Tract Urothelial Carcinoma, FGFR Gene Amplification, FGFR Gene Alteration, FGFR Gene Alterations, FGFR3 Mutation, FGFR3 Mutations, FGFR3 Gene Fusions
UT Southwestern
Phosphate Assessment in Chronic Kidney Disease Patients Study (PACK)
The proposed pilot feeding study aims to explore novel pathways in phosphate metabolism and identify new biomarkers, as well as to develop a compound index for assessing phosphate overload with high validity and reliability. Investigators will address the following specific aims: 1). To explore novel pathways of phosphate metabolism and assess the influence of CKD status on these metabolic pathways. 2). To identify novel biomarkers for phosphate overload that reflect changes in dietary phosphorus intake. 3). To develop a compound phosphate overload index that measures dietary phosphorus intake with high validity and reliability. This study will provide novel insights into phosphate metabolism and the assessment of phosphate overload in CKD patients. This investigation aims to provide preliminary data to further studies for the development of reliable biomarkers in CKD patients, which could contribute significantly to early interventions and improve health outcomes.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Paola.Lanza@UTSouthwestern.edu
Jing Chen
ALL
18 Years to old
NA
NCT07368946
STU-2024-1240
Inclusion Criteria:
* Men or women aged 18 years or older, of any race/ethnicity
* Women must either be post-menopausal or have no monthly menstrual cycle
* Estimated total daily energy expenditure (TDEE) of 1700 - 2700 calories
* eGFR \>15 ml/min/1.73m2 - \< 60 ml/min/1.73m2 for the CKD group (CKD Stage 3 or Stage 4)
* eGFR ≥ 60 ml/min/1.73m2 and negative urine protein on dipstick test for the non-CKD group
* English speaking
Exclusion Criteria:
* Pregnant, currently breastfeeding, or \<3 months postpartum
* Current dialysis or kidney transplant patient
* Current use of insulin or chemotherapy drugs
* Smokes cigarettes or uses e-cigarettes (vapes)
* Uses nicotine products or other recreational drugs
* Medical history of stroke or myocardial infarction (MI)
* Medical history of conditions that can affect phosphate metabolism (i.e., uncontrolled thyroid disorder, parathyroid disorder, or gastrointestinal malabsorption disorders \[Crohn's, ulcerative colitis, and celiac disease\], cirrhosis)
* Current use of certain medications that directly alter phosphate levels (i.e., phosphate binders; phosphate supplements, irregular use of iron)
* Regular use of laxatives
* Hypo- or hyperphosphatemia (serum phosphate \< 2.5 or \> 4.6 mg/dl)
* Hypo- or hypercalcemia (serum calcium \< 8.4 or \> 10.7 mg/dl)
* Severe anemia (hemoglobin \< 8 g/dl for women and \< 9 g/dl for men)
* Severe hyperglycemia (serum blood glucose \> 300 mg/dl)
* Body weight less than \<110 lbs (due to risk for phlebotomy-induced anemia)
* Received a blood transfusion in the last four months
* Extreme hypertension as demonstrated by a blood pressure \> 180/120 as the average of 3 blood pressures taken during the screening/baseline, or extremely low blood pressure \< 80/50
* Unwilling or unable to eat study meals
* Lack of access to a functional refrigerator or freezer
* Lack of access to a microwave or conventional oven
* On low potassium diet
* On low phosphate diet
* Specific dietary restrictions (i.e. vegetarian, vegan, ketogenic, etc.)
* Food allergies including but not limited to milk, egg, soy, nuts, shellfish, and wheat or gluten
* Allergic to sodium phosphate
* Unable or unwilling to complete urinary sample collection or food diaries
* Unable or unwilling to provide informed consent
* Unable to read or speak English
* Participant in other conflict clinical trial
* Unable to complete the study measurements
* Unsafe to participate in this study per investigator's judgement DIETARY_SUPPLEMENT: Dietary Phosphorus Intake
Chronic Kidney Disease (Stage 3-4), Chronic Kidney Disease Mineral and Bone Disorder
chronic kidney disease, study diet, feeding study, pilot, oral phosphate feeding
UT Southwestern
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Jordan.Roberts2@UTSouthwestern.edu
Markey McNutt
ALL
18 Years to 69 Years old
PHASE1
NCT07241234
STU20252082
Key
Inclusion Criteria:
* Diagnosis of PKU, defined as documented presence of 2 mutant alleles in the phenylalanine hydroxylase (PAH) gene, of which at least 1 is the R408W mutation, as determined during Screening per the genotyping performed by the study central genotyping laboratory.
* At least 1 plasma Phe concentration greater than (\>) 600 micromoles per liter (μmol/L) in the 52 weeks before providing informed consent.
* Average concentration of plasma Phe \> 600 μmol/L in Phe samples taken during Screening, with no individual assessment below 360 μmol/L. Any Phe samples taken after Day -20 will not be included.
* Body mass index (BMI) greater than or equal to (≥) 18.0 kilograms per meter square (kg/m\^2) to lesser than or equal to (≤) 35.0 kg/m\^2 and weight ≥ 50 kilograms (kg) at any time during the Screening Period.
* Documented approval from a dietitian confirming that the subject can maintain their diet consistent in protein and Phe intake throughout the study as outlined in the Diet Manual.
Key Exclusion Criteria:
* Prior exposure to AG-181.
* Receiving inhibitors of P-glycoprotein (P-gp) that have not been stopped for ≥ 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) before administration of the first dose of study drug.
* Receiving products that are strong inhibitors or strong inducers of cytochrome P450 CYP1A2, CYP2C8, or CYP3A that have not been stopped for ≥ 28 days before administration of the first dose of study drug.
* Receiving treatment with an acid-reducing agent, including but not limited to proton pump inhibitors and H2 blockers. Short-acting acid-reducing agents such as calcium carbonate are permitted.
* Any preexisting condition that could (in the opinion of the Investigator) interfere with gastrointestinal anatomy or motility that may disrupt the absorption, metabolism, and/or excretion of the study drug.
* Any preexisting condition that could (in the opinion of the Investigator) interfere with hepatic or renal function that may disrupt the absorption, metabolism, and/or excretion of the study drug.
* Inability to tolerate oral medication.
* Unwillingness to washout from tetrahydrobiopterin (BH4) supplementation (eg, sapropterin dihydrochloride, Kuvan), pegvaliase-pqpz (Palynziq), or any other PKU therapy by Day -30 during Screening. DRUG: AG-181
Phenylketonuria
UT Southwestern; Children’s Health
A Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician's Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer (Beacon-BTC)
This study is designed to 1) select a dose regimen for continued development and 2) evaluate nanvuranlat versus Physicians Best Choice (PBC) (FOLFOX, FOLFIRI, or Best Supportive Care (BSC)) in participants aged 18 years and over with BTC. Participants enrolling in Part A the trial will be randomly assigned to receive 1 of 3 nanvuranlat dose regimens or PBC. In Part B, participants will be randomly assigned to receive nanvuranlat or PBC. Participants will receive treatment every 2 weeks for as long as they do not experience safety issues, or their cancer gets worse, and the study doctor feels they should stop treatment. Health measurements including physical examinations, vital signs, ECGs, and safety laboratory tests will be performed to monitor safety, and tumor imaging will be performed to monitor cancer response to treatment. Other exploratory makers will be measured to better understand how nanvuranlat works.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years to old
PHASE3
NCT07265674
STU20252028
Inclusion Criteria:
\- Individuals are eligible to be included in the study only if all of the following criteria apply:
• At least 18 years of age inclusive at the time of signing the informed consent.
• Provides informed written consent according to local laws or regulations.
• Able and willing to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including peripheral blood and urine sampling during the study.
• Willing to participate in LAT1 testing and NAT2 and transporter genotyping. Note: For LAT1 testing, if the participant does not have archival tissue and a fresh biopsy is not in the best interest of the participant, they will still be eligible for the trial.
• Cancer must be metastatic, locally advanced and unresectable, or not amenable to treatment with local therapies that could offer a reasonable likelihood of clinical benefit.
• Histologic or cytologic diagnosis of BTC.
• Has BTC that is classified as either an IHC, EHC, or GBC based on surgical, clinical, or laparoscopic findings and/or radiological imaging (eg, CT, MRI).
• Has received 1 prior appropriate platinum (cisplatin, carboplatin, or oxaliplatin)-based therapy for advanced disease (locally advanced or metastatic) with or without a mAb targeting PD-1 or PD-L1.
• Disease progression during or within 6 months of neoadjuvant or adjuvant treatment with a platinum-containing regimen will count as having received 1 prior regimen.
• If a patient has a mutation/fusion of IDH1, FGFR2 or NTRK, or an amplified, mutated, or overexpressed form of HER2, or a recognized aberration in a validated "driver" of BTC, and was treated with an appropriate targeted agent, or the patient's tumor was determined to be MSI-H and an appropriate PD-1/PD-L1 mAb was administered, the targeted therapy or immunotherapy will NOT count as a separate line of treatment.
• ECOG PS of 0 or 1.
• Expected life expectancy of at least 90 days after the first day of treatment as per the site Investigator.
• At least 1 measurable lesion by RECIST v1.1 based on imaging (eg, CT, MRI) performed within 28 days prior to initiation of study intervention. Those who have received prior local therapy, including but not limited to embolization, chemoembolization, radiation therapy, and/or other appropriate ablative procedures to a measurable lesion that is within the treatment and shown ≥ 20% growth in size since posttreatment assessment.
• Resolution to ≤ Grade 1 by the NCI CTCAE v 5.0 (or higher) of all clinically significant toxic effects of prior chemotherapy or other treatments, except for alopecia and peripheral neuropathy (these must have resolved to ≤ Grade 2). If medical therapy is required for the treatment of a laboratory abnormality, the dose and laboratory value(s) should be stable.
• Adequate hematologic function:
• ANC ≥ 1.5 × 109/L. Myeloid growth factors must not have been administered within 7 days before the participant's first dose of study intervention.
• Hemoglobin ≥ 8.5 g/dL and no RBC transfusions during the 14 days before the participant's first dose of study intervention.
• Platelet count ≥ 100 × 109/L and no platelet transfusions during the 14 days before the participant's first dose of study intervention.
• Adequate baseline organ function, as demonstrated by the following:
• eGFR ≥ 50 mL/min as estimated by CKD-EPI 2021.
• Bilirubin ≤ 2 × ULN (local institution).
• AST and ALT ≤ 5 × ULN (local institution).
• Adequate coagulation function as defined by INR ≤ 1.5 OR a PT ≤ 1.5 × ULN AND an aPTT ≤ 1.5 × ULN if not receiving anticoagulation therapy. Note: Participants may receive subtherapeutic doses of warfarin while on study to maintain patency of venous devices but not with therapeutic doses of warfarin. Participants may be treated with low-molecular weight heparin.
• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and study follow up or for at least 9 months after the last dose of study intervention. Note: A woman is of nonchildbearing potential if she meets 1 of the following criteria: a) postmenopausal with at least 12 months of spontaneous amenorrhea; b) has had a bilateral oophorectomy; or c) has had a hysterectomy. Highly effective methods of contraception include: * Abstinence from sexual activity. * Hormonal contraception (eg, injection, implant, pill, patch, or vaginal ring as available in each country) associated with inhibition of ovulation (both estrogen and progestogen and progestogen only) in use for at least 30 days before administration of study intervention. * Intrauterine device in use for at least 30 days before administration of study intervention. * Intrauterine hormone-releasing system in use for at least 30 days before administration of study intervention. * Bilateral tubal occlusion/ligation at least 6 months before administration of study intervention. * Partner who has been vasectomized at least 6 months before administration of study intervention.
• Males and their female partners must use a highly effective method of birth control if female partner(s) is of childbearing potential, and males must not donate sperm during the study and for 9 months after the last dose of study intervention.
Exclusion Criteria:
* Individuals will be excluded from study participation if they meet any of the following criteria:
• Received systemic therapy or an investigational agent before washing out, as follows:
• \< 2 weeks prior to Cycle 1 Day 1 for systemic non-immune-based therapy
• \< 3 weeks prior to Cycle 1 Day 1 for immune-based therapy
• ≤ 5 half-lives or 3 weeks (whichever is longer) prior to Cycle 1 Day 1 for an investigational agent
• Received radiotherapy to metastatic sites within 2 weeks of Cycle 1 Day 1. Patients must have recovered from all radiation-related toxicities and not require corticosteroids. A 1 week washout is permitted for palliative radiation with a limited port ≤ 2 weeks of radiotherapy to non-CNS disease.
• Underwent hepatic radiation, chemoembolization, or radiofrequency ablation \< 4 weeks prior to Cycle 1 Day 1.
• Underwent major surgery \< 3 weeks before Screening and has not recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• Known active CNS metastases and/or carcinomatous meningitis. Those with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of PD for at least 4 weeks by repeat imaging), clinically stable, and without requirement of corticosteroid treatment for at least 14 days prior to first dose of study intervention. For those with a history of CNS involvement, repeat imaging should be performed during study screening. However, CNS imaging is not required prior to study entry unless there is clinical suspicion of CNS involvement.
• Clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart Association Class 3 or 4 heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• Resting QTcF \> 470 msec at screening.
• An additional active malignancy that is progressing or has required active treatment within the past 3 years. Cases involving a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, breast cancer, and melanoma in situ), organ-confined prostate cancer with no evidence of PD.
• Require strong inhibitors of P-gp, BCRP, OATP1B1, OATP1B3, OATP1A2, and OAT3 transporters unless they can be transferred to other medications within ≥ 5 half-lives of treatment.
• Require sensitive substrates of OATP1B1 and OATP1B3 unless they can be transferred to other medications within ≥ 5 half-lives of treatment.
• Known positive status for HIV, has not been treated with established appropriate antiretroviral therapy for at least 4 weeks, and has a hydrophobic interaction chromatography viral load \< 400 copies/mL and a CD4+ T-cell (CD4+) counts ≥ 350 cells/µL prior to enrollment. No HIV testing is required unless mandated by local health authority.
• Active or chronic HBV and active (not cured) HCV. Participants who are HBV carriers without active disease (HBV DNA titer \< 1000 copies/mL or 200 IU/mL) or cured HCV (negative HCV RNA test) with confirmed viral clearance that are not receiving ongoing treatment and without residual chronic liver disease may be enrolled.
• An uncontrolled intercurrent illness including, but not limited to medical illness; uncontrolled infection requiring therapy; psychiatric illness; alcohol or drug dependence; social situations or a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator or Medical Monitor.
• Requires therapeutic doses of warfarin (ie, requires monitoring). A washout period of 7 days before administration of a participant's first dose of study intervention is required for those in whom therapeutic doses of warfarin are discontinued. Note: Warfarin at a low daily dose to maintain patency for indwelling venous catheters is allowed. Low-molecular weight heparin and direct-acting oral anticoagulants, according to the inclusion requirements pertaining to coagulation test results, are allowed.
• Clinically significant edema or intracavitary fluid collections (eg, ascites, pleural effusion, pericardial effusions) resulting in moderate symptoms and/or requiring frequent drainage.
• Previously developed shock, anaphylaxis, or renal disorder due to SBECD.
• WOCBP who is pregnant, lactating, or discontinued lactation \< 12 weeks prior to Screening, or who plans to become pregnant or initiate lactation during the study.
• Known reaction or contraindication to any component of study intervention (ie, oxaliplatin, leucovorin \[including levoleucovorin\], and 5-FU \[FOLFOX\] and irinotecan, leucovorin, and 5-FU \[FOLFIRI\]).
• Known DPD deficiency. Screening for DPD deficiency is not mandated but should be considered in subjects who have had severe toxicity due to fluoropyrimidine-based therapy in the past.
DRUG: Nanvuranlat, OTHER: Physician's Best Choice
Advanced Biliary Tract Cancer, Biliary Tract Cancer (BTC), Liver, Other Digestive Organ
Intrahepatic cholangiocarcinoma (IHC), Extrahepatic cholangiocarcinoma (EHC), Gallbladder carcinoma (GBC)
UT Southwestern
A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer (KLK2-PASenger)
The purpose of this study is to find out whether treatment with pasritamig and docetaxel prolongs radiographic progression free survival (rPFS) (the length of time from start of treatment until disease worsens as determined by scans or death due to any cause) when compared to treatment with docetaxel in participants with metastatic castrate-resistant prostate cancer (mCRPC; a cancer of prostate, a male reproductive gland found below the bladder, that grows despite low levels of male hormones).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years to old
PHASE3
NCT07225946
STU20260209
Inclusion criteria:
* Have histologically confirmed adenocarcinoma of the prostate
* Have disease that is metastatic at the time of screening by computed tomography (CT) or magnetic resonance imaging (MRI) and 99m\^Tc bone scan as determined by the investigator
* Participants must receive ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) analog throughout the treatment or have had prior bilateral orchiectomy, and have serum testosterone less than or equal to (\<=) 50 nanogram per deciliter (ng/dL) (\<= 1.73 nanomoles per Liter \[nmol/L\]) at screening
* Have progressed by PSA or CT/MRI or 99m\^Tc bone scan on at least 1 novel androgen receptor pathway inhibition (ARPI) but no more than 2 different ARPI for any stage of disease. Must have discontinued ARPI before randomization into the study
* Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1
Exclusion criteria:
* Known history of either brain or leptomeningeal prostate cancer metastases
* Participants with known breast cancer gene 1/2 (BRCA 1/2) mutations (germline or somatic) who have not received treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor, unless not available or contraindicated
* Prior or concurrent second malignancy (other than the disease under study)
* Received cytotoxic chemotherapy for prostate cancer in any setting
* Received prior treatment with human kallikrein 2 (KLK-2) directed therapies
DRUG: Pasritamig, DRUG: Docetaxel, DRUG: Prednisone/Prednisolone
Prostatic Neoplasms, Castration-Resistant, Prostate
UT Southwestern
A Safety, Tolerability, and Biomarker Trial of VS-041 in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF)
A Safety, Tolerability, and Biomarker Trial of VS-041 in Participants with Heart Failure with Preserved Ejection Fraction (HFpEF)
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Serrano@UTSouthwestern.edu
Alvin Chandra
ALL
50 Years to old
PHASE1
NCT07219511
STU20252022
Inclusion Criteria:
Participants must meet all inclusion criteria to be eligible for trial participation.
• Males or females ≥ 50 years of age at the time of signing the informed consent.
• Diagnosis of HFpEF as defined by European Society of Cardiology or American College of Cardiology/American Heart Association criteria
• NYHA Functional Class II or III
• LVEF ≥ 50% demonstrated by echocardiography (ECHO) performed at Screening with evidence of heart failure
• Elevated NT-proBNP at Screening
• NordicPRO-C6™ ≥ 11 ng/mL at Screening.
• Stable dose of all concomitant HF medications for at least 4 weeks prior to Screening.
• Body weight of at least 110 lbs (50 kg) and body mass index (BMI) within the range ≥ 18 to \< 45 kg/m2.
• Males must agree to the contraception requirements and females must be of non-childbearing potential
• Able to understand and willing to sign a written informed consent form (ICF).
• Willing and able to comply with trial procedures and restrictions listed in the ICF and in this protocol.
Exclusion Criteria:
• Female trial participant who is pregnant or breastfeeding.
• Known hypersensitivity to VS-041.
• Cardiovascular disease other than HFpEF
• Active intercurrent illness such as acute bacterial or viral infection.
• History of illicit drug or alcohol abuse or addiction that in the opinion of the PI could affect participation.
• Active chronic viral infection such as Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) at Screening.
• Acute decompensated HF within 30 days of Screening
• Lung disease within 12 months prior to Screening
• History of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.
• History of any other condition including psychiatric disorders that, in the opinion of the PI, may preclude the participant from following and completing the protocol.
• Have participated within the last 6 months in a clinical study involving an investigational product.
• Any other reason which, in the opinion of the PI, would prevent the participant from participating in the trial.
DRUG: VS-041, OTHER: Placebo
Heart, Heart Failure With Preserved Ejection Fraction (HFpEF)
Heart Failure with Preserved Ejection Fraction, HFpEF
UT Southwestern
A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation (TRANSPIRE)
In this study, researchers will learn more about a drug called felzartamab in people who have received a kidney transplant and later developed a condition called microvascular inflammation (MVI). MVI is a type of injury to small blood vessels in the transplanted kidney and may be a sign of rejection by the body. It can lead to serious kidney problems over time. In many cases, MVI is caused by antibodies that attack the transplanted kidney. But in some people, MVI happens without these antibodies. This type of MVI is called isolated MVI. There are currently no approved treatments for isolated MVI. The main goal of the study is to learn about the effect felzartamab has on inflammation in the transplanted kidney. The main question researchers want to answer is: • How many participants have no signs of active inflammation in the transplanted kidney after 24 weeks of treatment with felzartamab? Researchers will also study how felzartamab affects kidney function, immune activity, and overall health. They will monitor safety through kidney biopsies, lab tests, and by recording adverse events throughout the study. Adverse events are health problems that may or may not be caused by the study drug. The study will be done in 2 parts as follows: * Participants will be randomly assigned to receive either felzartamab or a placebo. A placebo looks like the study drug but contains no real medicine. * In Part A, participants will receive their assigned drug for 24 weeks. Neither the researchers nor the participants will know who is receiving felzartamab or placebo. * Part B will last another 28 weeks. All participants will receive felzartamab and both participants and researchers will know this. * All treatments will be given by intravenous (IV) infusion at the study site. * Participants will have kidney biopsies at the start of the study, at Week 24, and at Week 52 to help measure changes in inflammation. * Participants will stay in the study for about 1 year.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Elaine.Bonilla@UTSouthwestern.edu
David Wojciechowski
ALL
18 Years to 74 Years old
PHASE2
NCT07219043
STU20252037
Key
• Adequate: 10 or more non-sclerotic/evaluable glomeruli and two muscular arteries
• Minimally Adequate: at least 7 non-sclerotic/evaluable glomeruli and one muscular artery * For participants who received any prior treatment for antibody-mediated rejection (AMR), MVI, or TCMR as outlined in Exclusion Criterion 5, the biopsy must be performed at least 6 weeks after completing (or stopping) prior treatment. * Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors). * DSA: Human leukocyte antigen (HLA) Class I and II antigen-specific DSA-negative (preformed and de novo DSA) as determined by the local laboratory's definition of positivity using single-antigen bead-based assays within 3 months prior to randomization. Key
• Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or plasma exchange (PLEX).
• Complement system inhibitors (e.g., eculizumab).
• Proteasome inhibitors (e.g., bortezomib).
• The anti-interleukin-6 receptor (anti-IL-6R) tocilizumab.
• Any B cell-depleting therapy (including anti-CD20 agents \[e.g., rituximab\]) within 3 months prior to randomization.
• Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization. Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria:
* MVI (MVI ≥2), donor specific antibody (DSA)-negative that is either complement activation (C4d) negative or C4d positive (biopsy-confirmed) without T cell-mediated rejection (TCMR) per central reading, as defined by the Banff 2022 criteria.
* Biopsy must be within 3 months (preferably within 1 month) prior to randomization and meet adequate criteria (option a preferred over option b):
• Adequate: 10 or more non-sclerotic/evaluable glomeruli and two muscular arteries
• Minimally Adequate: at least 7 non-sclerotic/evaluable glomeruli and one muscular artery * For participants who received any prior treatment for antibody-mediated rejection (AMR), MVI, or TCMR as outlined in Exclusion Criterion 5, the biopsy must be performed at least 6 weeks after completing (or stopping) prior treatment. * Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors). * DSA: Human leukocyte antigen (HLA) Class I and II antigen-specific DSA-negative (preformed and de novo DSA) as determined by the local laboratory's definition of positivity using single-antigen bead-based assays within 3 months prior to randomization. Key
Exclusion Criteria:
* Transplant: Blood type (ABO)-incompatible transplant.
* History of multiple organ transplants including en bloc and dual kidney transplants.
* Presence of HLA donor-specific antibodies.
* Acute, rapid decline in renal function, defined as a participant likely to require renal replacement therapy within the next 30 days as determined by the Investigator.
* Prior AMR or TCMR treatment (with the exception of corticosteroids) within 3 months prior to randomization is excluded as listed below. Participants who received any of these treatments between 3 and 6 months prior to randomization must have both a renal biopsy (IC3) and DSA testing at least 6 weeks after completing (or stopping) treatment in order to confirm continuing MVI≥2 and DSA negative status and to determine eligibility:
• Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or plasma exchange (PLEX).
• Complement system inhibitors (e.g., eculizumab).
• Proteasome inhibitors (e.g., bortezomib).
• The anti-interleukin-6 receptor (anti-IL-6R) tocilizumab.
• Any B cell-depleting therapy (including anti-CD20 agents \[e.g., rituximab\]) within 3 months prior to randomization.
• Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization. Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
DRUG: Felzartamab, DRUG: Placebo
Microvascular Inflammation
Kidney Transplant, Kidney Transplant Rejection
UT Southwestern