The purpose of this study is to collect long-term follow-up data on delayed adverse events after administration of ciltacabtagene autoleucel (cilta-cel), and to characterize and understand the long-term safety profile of cilta-cel.

Type: Interventional

Start Date: Mar 2022

open study

The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in combination with standard of care options for the treatment of rrDLBCL. This study will be divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx with respect to progression-free survival (PFS) per Lugano response criteria by blinded independent review committee (BICR); and that ZV in combination with bendamustine rituximab (BR) is superior to BR with respect to PFS per Lugano response criteria by BICR. With protocol amendment 4 (effective: 04-April-2024), enrollment in Cohort B (study arms Bendamustine Rituximab [BR] and ZV + BR) is discontinued. No efficacy outcome analysis and hypothesis testing will be conducted for Cohort B.

Type: Interventional

Start Date: Jan 2022

open study

The purpose of this research is to examine the effects of two different exercise training regimens for managing depression and improving other health indicators among persons with multiple sclerosis (MS). The project will enroll persons with MS and major depressive disorder (MDD) between 18 and 64 years of age. The investigators will enroll a total of 146 participants. This is a Phase-II trial that compares the efficacy of an exercise training program (POWER-MS) compared with a stretching program (FLEX-MS) for immediate and sustained reductions in the severity of depression among persons with MS who have MDD.

Type: Interventional

Start Date: Apr 2023

open study

Background: Smith-Lemli-Opitz Syndrome (SLOS) is a genetic disorder. It can cause birth defects and developmental delays. There is no cure for SLOS or other inherited diseases related to cholesterol production or storage. The data gained in this study may help researchers find ways to measure how well future treatments work. Objective: To learn more about SLOS and related disorders and how these diseases affect participants and relatives. Eligibility: People of any age who have or are suspected to have SLOS or another inherited disease related to cholesterol production or storage. Relatives are also needed. Design: Participants will be screened with a medical record review. Participants will have visits every 6 to 12 months. They will have a physical exam. They will fill out a survey about their medical and behavioral history. They may have an eye exam. They may have a neurodevelopmental assessment. They may have a hearing test. Their outer and middle ears may be examined. Their ability to speak, understand speech, eat, and swallow may be assessed. They may get X-rays while they chew and swallow. Their functional ability and needs for adaptive devices or braces may be assessed. They may have a lumbar puncture. Photographs may be taken of their face and body. Participants who cannot visit the NIH and relatives will have a virtual visit once a year. They will talk about their medical history and symptoms. They give blood, urine, and skin samples at a lab near their home. They will fill out a survey about their medical and behavioral history. Participation will last for several years.

Type: Observational

Start Date: Jun 2021

open study

The goal of this clinical study is to learn more about the safety and effectiveness of the study drugs, KITE-363 and KITE-753, in participants with relapsed and/or refractory B-cell lymphoma.

Type: Interventional

Start Date: Oct 2021

open study

The purpose of this study is to assess the safety, tolerability, and recommended dose(s) of BMS-986340 as monotherapy and in combination with nivolumab, docetaxel, or Pumitamig in participants with advanced solid tumors. This study is a first-in-human (FIH) study of BMS-986340 in participants with advanced solid tumors.

Type: Interventional

Start Date: May 2021

open study

This research study will add an anti-cancer drug (called inotuzumab ozogamicin also known as "InO") to treatment for participants with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Doctors leading this study hope to learn if adding InO to standard induction treatment for Ph+ ALL will lead to quicker, complete molecular remission (where the disease is not detectable even with very sensitive testing techniques). The purpose of this research is to gather information regarding the effectiveness of InO in newly-diagnosed Ph+ ALL patients that have not yet received treatment.

Type: Interventional

Start Date: Mar 2021

open study

This phase I trial identifies the side effects and best dose of DS-8201a and olaparib in treating patients with HER2-expressing cancers that have spread to other places in the body or cannot be removed by surgery or ovarian cancer that remains despite treatment with a platinum treatment (platinum resistant). Olaparib is a drug that blocks an enzyme involved in many cell functions, including the repair of deoxyribonucleic acid (DNA) damage. Blocking this enzyme may help keep tumor cells from repairing their damaged DNA, causing them to die. DS-8201a is an antibody-drug conjugate. This agent has two components: an antibody component and a chemotherapy component. The antibody component is attached to the chemotherapy molecules. Upon administration of DS-8201a, the antibody targets and binds to tumor cells that have abundant HER2 (human-epidermal growth factor receptor 2), which is a protein on the surface of some tumor cells. The chemotherapy then enters the cells and blocks DNA replication in the tumor cells with abundant HER2, causing them to die. Giving DS-8201a and olaparib may shrink or stabilize the cancer.

Type: Interventional

Start Date: May 2021

open study

This study will compare the effectiveness of osimertinib alone with the combination of osimertinib and chemotherapy (carboplatin and pemetrexed) in people with metastatic lung cancer that has a change (mutation) in the gene EGFR. Osimertinib alone is the usual treatment for metastatic EGFR-mutant lung cancer. Researchers think adding chemotherapy to osimertinib could possibly add to the anticancer effects of the usual treatment and help stop cancer from growing or spreading.

Type: Interventional

Start Date: May 2020

open study

This is a pilot study using cytotoxic T lymphocytes (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Gamma-capture system will be effective in decreasing specific viral load in patients with BK virus viremia and BK virus-associated symptoms post-allogeneic hematopoietic stem cell transplantation (HSCT), renal transplantation, and chemotherapy.

Type: Interventional

Start Date: Oct 2019

open study

Primary sclerosing cholangitis (PSC) is a rare liver disease that damages the liver's bile ducts. Bile ducts are tiny tubes that carry bile from the liver to the small intestine. Bile is a liquid produced by the liver that helps us absorb and use the nutrients in the food we eat. In people with PSC, the bile backs up into the liver and will damage it, causing scarring of the liver. The purposes of this study are to: - Collect medical and other data to learn more about PSC, how it progresses, and identify factors that may cause the disease to progress more quickly. - Ask questions about how PSC symptoms affect your child's life to learn more about its impact on your child's daily functioning - Children with PSC who are seen at one of the participating clinical sites in the Childhood Liver Disease Research Network (ChiLDReN) will be asked to contribute information, DNA, and other specimens. The information and specimens will be available to investigators to carry out approved research aimed at learning more about the possible causes and long-term effects of PSC.

Type: Observational

Start Date: Dec 2021

open study

Obstructive sleep apnea (OSA) and Chronic Obstructive Pulmonary Disease (COPD) are highly prevalent chronic respiratory diseases in the Veteran population. OSA co-occurring with COPD, known as Overlap Syndrome (OVS), is a complex chronic medical condition associated with grave consequences. OVS is highly prevalent in Veterans. Veterans with OVS may be at increased risk for cognitive deficits, poor sleep quality as well as a reduced quality of life (QoL). The overall objective is to study the effects of positive airway pressure therapy on clinical outcomes in patients with OVS.

Type: Interventional

Start Date: Dec 2020

open study

Pediatric weight management efficacy is impacted by failure to complete treatment protocols and, for those that do complete treatment, a return to unhealthy behaviors. This project tests whether treating pain, a common comorbid condition to pediatric obesity, will enhance treatment. This study will generate results that can be translated into immediate improvements in care for families seeking treatment for pediatric obesity.

Type: Interventional

Start Date: Aug 2019

open study

This is a study to assess the effect of dietary zinc supplementation to mitigate biomarkers of metal toxicity in exposed tribal populations.

Type: Interventional

Start Date: May 2019

open study

This trial studies how well the diagnostic deoxyribonucleic acid (DNA) methylation signature works in detecting thyroid cancer in patients with thyroid nodules. Using diagnostic testing, such as the diagnostic DNA methylation signature, may be a less invasive way to check for thyroid cancer.

Type: Observational

Start Date: Jan 2027

open study

This is a prospective study for the long-term follow-up (LTFU) of safety and efficacy for all pediatric and adult participants exposed to Gene-modified (GM) T-cell therapy participating in a previous Celgene sponsored or Celgene alliance partner sponsored study. Participants who received at least one infusion of GM T cells will be asked to enroll in this LTFU protocol upon either premature discontinuation from, or completion of the prior parent treatment protocol.

Type: Interventional

Start Date: Jul 2018

open study

The purpose of this study is to investigate whether cells from a biopsy taken from the patient skin can be transformed into cardiomyocytes the changes in cardiomyocyte (heart muscle cells) when grown in a special culture medium outside of the body. The structure and function of these cells will then be studied to determine why some patients with breast cancer who are treated with chemotherapy including anthracycline (e.g. Doxorubicin) and anti-HER2 therapy (e.g. Herceptin) develop decreased heart function.

Type: Observational

Start Date: May 2016

open study

Demonstrate the impact of the Molecular Microscope Diagnostic System as the standard of care for heart transplant patients.

Type: Observational

Start Date: Jan 2016

open study

This phase II trial studies how well vismodegib, focal adhesion kinase (FAK) inhibitor GSK2256098, and capivasertib work in treating patients with meningioma that is growing, spreading, or getting worse (progressive). Vismodegib, FAK inhibitor GSK2256098, capivasertib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Type: Interventional

Start Date: Sep 2015

open study

The goal of this phase II study is to investigate the feasibility, toxicity and efficacy of a regimen incorporating a proven systemic regimen, carboplatin /paclitaxel, with conformal proton modality, followed by definitive surgery. In most combined-modality trials to date, chemotherapy regimens have included cisplatin, usually in conjunction with 5-fluorouracil. In designing the regimen, the investigators attempt to improve on the standard cisplatin/5-fluorouracil regimen in several ways. First, full-dose paclitaxel is added to the regimen. This agent has activity against advanced esophageal cancer and is also a potent radiosensitizer. Second, the substitution of carboplatin for cisplatin has resulted in reduced toxicity of various combination regimens similar to that used by CROSS trial and allows for easier administration in the outpatient setting.4 Third, for localized esophageal cancer, dose distribution patterns achievable with proton beam could potentially offer important clinical advantages relative to those achievable with x-rays (photons).19 Based on this, the investigators believe that this study should be conducted with the radiation modality that offers the best dosimetry achievable at our institution.

Type: Interventional

Start Date: Feb 2013

open study

Background: Human intestines are home to a complex gut flora, also called microbiome; this is a natural occurring community of bacteria, fungi, yeast, and viruses. Changes in the balances of the gut flora can lead to illnesses, such as diabetes, colorectal cancer, and inflammatory bowel diseases. Synbiotics are dietary supplements people take to maintain proper balances of their gut flora aiming to improve health. Objective: To find out if a synbiotic supplement can increase the type and amount of beneficial gut bacteria in healthy people as well as improve cardio-vascular protection markers. The supplement contains a natural sugar from human milk. Eligibility: Healthy people aged 18 years or older who eat a typical western diet. They must take no medications (with a few exceptions). Design: Participants will have 2 clinic visits. The first visit will start with screening. They will have a blood test and wait around 2 hours for the results of the blood test. The test will determine if they are eligible for the study. Eligible participants will have additional blood drawn during the screening visit. They will be given a kit to collect a stool sample at home with instructions. They may complete a 3-day food diary. They will meet with a nutritionist and a physician by phone, telehealth, or in person. The supplement is a powder that is mixed with water or another noncarbonated drink. Participants will drink 2 doses per day. Each dose will be 1 hour before or after a meal. The second visit will be about 8 weeks after the first. Participants may repeat the 3-day food diary and nutrition visit. The physical exam, blood tests, and stool sample will be repeated.

Type: Interventional

Start Date: Nov 2024

open study

Background: Prostate cancer may return after treatment in 30,000 to 50,000 people each year. There is no clear best way to treat these people. Better treatments are needed. Objective: To test a study drug (enzalutamide), both alone and combined with a second drug (PDS01ADC), in people with prostate cancer that returned after treatment. Eligibility: People aged 18 years and older with prostate cancer that returned after treatment. Design: Participants will be screened. They will have a physical exam, with blood tests. All their urine will be collected for 24 hours. They will have imaging scans of their chest, abdomen, pelvis, and bones. Their ability to perform everyday activities will be assessed. They may opt to give a stool sample. Participants will be treated in 4-week cycles. Enzalutamide is a pill taken by mouth once a day, every day. All participants will be given a supply of this drug to take at home. PDS01ADC is injected under the skin once a month, on the first day of each cycle. Half of the participants will receive both drugs. All participants will visit the clinic once a month. Each visit should last no more than 8 hours. Blood and urine tests will be repeated. All participants will receive the study treatment for 3 cycles. Some participants may need 3 more cycles of treatment with enzalutamide only. This re-treatment can be done only once. Participants will have a follow-up visit 1 month after they finish treatment. After that, they will have visits every 6 weeks for up to 5 years. Imaging scans and blood tests will be repeated. ...

Type: Interventional

Start Date: Apr 2024

open study

Background: Cancers of the nasal cavity or skull base are rare. They often are not diagnosed until they are at an advanced stage, and they often spread to other parts of the body. These cancers may have mutations in a gene called IDH2. Researchers want to find out if a drug (enasidenib) that targets the IDH2 mutation can help people with these cancers. Objective: To test enasidenib in people with cancers of the nasal cavity or skull base. Eligibility: People aged 18 years and older with rare cancers of the nasal cavity or the base of the skull. Their cancer must have an IDH2 gene mutation, and it must have recurred locally or spread to other parts of the body. These cancers can include sinonasal undifferentiated carcinoma; olfactory neuroblastoma; sinonasal large-cell neuroendocrine carcinoma; poorly differentiated sinonasal adenocarcinoma; or chondrosarcoma. Design: Participants will be screened. They will have a physical exam with blood and urine tests and tests of their heart function. They will have imaging scans of their brain, skull base, neck, chest, abdomen, and pelvis. A sample of tumor tissue will be collected. Enasidenib is a tablet taken by mouth with a glass of water. Participants will take the drug once a day, every day, in 28-day cycles. They will not have resting periods between cycles. Participants will visit the clinic on the first day of each cycle to receive the tablets they will need to take at home until the beginning of the next cycle. They will keep a diary to record the time of each dose they take. Participants may remain in the study as long as the drug is helping them....

Type: Interventional

Start Date: Mar 2024

open study

Background: Chronic hepatitis B virus (HBV) infection affects 292 million people worldwide; 887,000 die each year from cirrhosis, liver cancer, and related issues. Treatment options are limited. Objective: To test 2 drugs (VIR-2218 and peginterferon) in people with mild or inactive HBV infection. Eligibility: People aged 18 to 65 years with mild or inactive HBV infection. Design: Participants will be screened. They will have blood tests and an eye exam. They will have imaging scans of the liver to check the health of the liver. Participants will be in the study for over 2 years. VIR-2218 is an injection given under the skin of the stomach, upper arm, or thigh. Participants will come to the clinic to receive this injection once a month for 6 months. Peginterferon is also injected under the skin. Participants will have this shot once a week for 6 months. They may either inject themselves at home or come to the clinic to get the injections. Participants will get just the VIR-2218 for 3 months, then both shots for 3 months, then just the peginterferon for 3 months. Participants will have two 3-day stays in the hospital. Tests will include: Liver biopsy. A sample of tissue will be taken from their liver. After the procedure, participants will lie on their right side for 2 hours and then on their back for 4 hours. Fine needle aspiration. A small needle will be used to collect cells from the liver. After the last injection of peginterferon, follow-up visits will continue in the outpatient clinic every 4 to 12 weeks.

Type: Interventional

Start Date: Jan 2025

open study

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses. Objective: To test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL. Eligibility: People aged 3 to 39 with ALL or related B-cell lymphoma that has not been cured by standard therapy. Design: Participants will be screened. This will include: Physical exam Blood and urine tests Tests of their lung and heart function Imaging scans Bone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone. Lumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord. Participants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells. Participants will receive chemotherapy starting 4 or 5 days before the CAR treatment. Participants will be admitted to the hospital. Their own modified T cells will be returned to their body. Participants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years....

Type: Interventional

Start Date: Dec 2022

open study