Clinical Research Directory

Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants

This study will provide follow-up evaluation and care of patients who have undergone allogeneic (donor) stem cell transplantation at the NIH Clinical Center. Patients are monitored for their response to treatment, disease relapse, and later-occurring effects of the transplant. Patients between 10 and 80 years of age who received a donor stem cell transplant at the NIH Clinical Center under an NHLBI protocol may be eligible for this study. Candidates must have had their first transplant at least 3 years before entering the current study. Participants are generally seen in the clinic every 12 months for some or all of the following procedures: * Periodic physical examinations, eye examinations, and blood and urine tests. * Bone marrow aspiration and biopsy: A sample of bone marrow is obtained for microscopic examination. The patient is given local anesthesia or conscious sedation. An area of the hipbone is numbed, a thin needle is inserted through the skin into the bone, and a small amount of marrow is withdrawn. * Tissue biopsy: A small piece of tissue or tumor is obtained for microscopic examination. Depending on the site of the biopsy, the tissue may be removed using a cookie cutter-like "punch" instrument, a needle, or a knife. The area is numbed and the tissue is removed with the appropriate tool. * Imaging tests to visualize organs, tissues, and cellular activity in specific tissues. For these tests, the patient lies on a table that slides into the scanner. They may include the following: 1. Nuclear scans use a sensitive camera to track a small amount of radioactive material (radioisotope) that is given to the patient by mouth or through a vein. The scan may show abnormal areas of tissue in the bones, liver, spleen, kidney, brain, thyroid, or spine. 2. Magnetic resonance imaging (MRI) uses a magnetic field and radio waves to examine small sections of body organs and tissues. 3. Computerized tomography (CT) uses x-rays and can be done from different angles to provide a 3-dimensional view of tissues and organs. 4. Positron emission tomography (PET) uses a fluid with a radioisotope attached to it to show cellular activity in specific tissues. The fluid is given through a vein and travels to the cells that are most active (like cancer cells), showing if there is an actively growing tumor. * Pulmonary (lung) function tests: The patient breathes into a machine that measures the volume of air the person can move into and out of the lungs. * Heart function tests may include the following: 1. Electrocardiogram (EKG) evaluates the electrical activity of the heart. Electrodes placed on the chest transmit information from the heart to a machine. 2. Echocardiogram (Echo) is an ultrasound test that uses sound waves to create an image of the heart and examine the function of the heart chambers and valves. 3. Multiple gated acquisition scan (MUGA) is a nuclear medicine test that uses a small amount of radioactive chemical injected into a vein. A special scanner creates an image of the heart for examining the beating motion of the muscle. Disease relapse or progression, or transplant-related problems may be treated with standard medical, radiation, or surgical therapy, or patients may be offered experimental therapy.

Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in Refractory Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Background: Chronic graft-versus-host disease (cGVHD) is an immune system disorder that can occur in people who have had a stem cell transplant. cGVHD can affect multiple organs and increase risk of disability and death. New treatments are needed to treat cGVHD after stem cell transplant. Objective: To test a drug (pacritinib) in people with moderate or severe cGVHD that has not responded to previous treatment. Eligibility: People aged 18 years and older with moderate or severe cGVHD that has not responded to 2 or more lines of previous treatment. Design: Participants will be screened. They will have blood and urine tests. They will have tests of their heart and lung function. They may also have a CT scan. Some may have other specialized tests. Participants will take the study drug at home every day. Pacritinib is a capsule taken by mouth. The study doctor will determine the dosage and schedule. Participants will keep a medication diary. They will record the date and time of each drug dose and any missed doses. Participants will visit the clinic every 2 weeks for the first 4 months. Then they will visit the clinic once every 4 weeks. They will have blood and urine tests. During some visits, other screening tests will be repeated, and participants will fill out questionnaires about their quality of life. Photographs may be taken of skin rashes and joints affected by cGVHD. Participants will give saliva samples. Optional biopsies may be taken of the skin and mouth. Participants will take pacritinib for 6 to 12 months if no side effects develop. Follow-up visits will continue for up to 2 years. ...

Chronic GVHD Response Measures Validation

The purpose of this study is to develop and validate endpoint measures that can accurately determine whether patients are responding to treatment for chronic Graft-versus-Host Disease (GVHD). Hopefully, this will also lead to being better able to predict which patients will respond to what therapies.

Pediatric cGVHD Symptom Scale

Background: Some children/adolescents who have had a stem cell transplant live with chronic graft-versus-host-disease (cGVHD). cGVHD is a side effect of the transplant that can cause multiple bothersome symptoms and negatively affect a child/adolescent squality of daily life. The questionnaires that measure thesymptoms caused by cGVHD are designed for adults. Children/adolescents may not describe their symptoms in the same way. The goal of this research is to improve the way we measure how bothersome these symptoms are for children/adolescents living with cGVHD. Objective: To develop a questionnaire (The Pediatric cGHVD Symptom Scale) for children/adolescents living with cGVHD to identify the symptoms they are experiencing and describe how bothersome those symptoms are to them. An additional goal is to design a parent/guardian companion questionnaire that can be used to capture the symptom experiences of very young children who may not be able to complete a questionnaire. Eligibility: Children/adolescents ages 5-17 who are receiving treatment for cGVHD after a stem cell transplant, and their parent/guardian.. Design: This study consists of 2 projects. Children/adolescents with cGVHD and their parent/guardianparticipants will be grouped by the child/adolescent s age: 5-7, 8-12, and 13-17. In project 1, participants will complete an age-appropriate questionnaire about cGVHD symptoms. The questionnaire will ask about the child/adolescent s physical functioning and emotional well-being. The parent/guardian will out fill out a companion questionnaire online. The child/adolescent will then review their completed questionnaire during an interview with a researcher and will be asked whether the questions about their symptoms were difficult to understand. The parent/guardian and child/adolescent will then be interviewed together to further explore their responses to the questionnaires. Interviews will be done in person, by phone, and online. . Based on what is learned through these interviews, the wording of the questionnaire will be improved for better comprehension and ease of response. In project 2, participants will complete this revised questionnairefor their age group along with some other questionnaires that ask about quality of life. Both the child/adolescent and parent/guardian will fill out the questionnaires online at three separate time points. In both projects, children/adolescents with cGVHD and their parent/guardian participants will be grouped by the child/adolescent s age: 5-7, 8-12, and 13-17. ...

Fecal Microbiota Transplantation for Steroid-Refractory Acute GI GVHD

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for various hematologic diseases. However, one of the major challenges of allo-HSCT is the occurrence of graft-versus-host disease (GvHD), particularly acute gastrointestinal GvHD (GI-GvHD). GvHD occurs when donor T cells recognize the recipient's tissue as foreign and mount an immune attack against it. Acute GI-GvHD is a common complication following allo-HSCT and a significant cause of mortality. If the initial steroid treatment for acute GvHD fails, mortality rates can reach as high as 81%. Recent studies have shown a strong association between reduced gut microbiota diversity and high mortality in patients with acute GI-GvHD, highlighting the critical role of the gut microbiome in regulating immune responses and maintaining intestinal homeostasis. Consequently, fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy aimed at restoring a healthy gut microbiome and improving clinical outcomes in patients with acute GI-GvHD. This study aims to evaluate the efficacy and safety of FMT in patients with steroid-refractory or steroid-resistant acute GI-GvHD. The findings of this research will contribute to establishing FMT as a potential and effective treatment option for managing severe acute GI-GvHD, thereby improving patient outcomes and reducing transplant-related mortality.

HCMV-miRNA Monitoring After Allogeneic Hematopoietic Stem Cell Transplantation Using PSTM-qPCR

Human cytomegalovirus (HCMV) infection is one of the most common and serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Standard monitoring uses HCMV DNA testing, but this method may not detect the virus early enough to guide timely treatment. This multicenter observational study will evaluate a new high-performance microRNA (miRNA) detection technology (PSTM-qPCR) for monitoring HCMV infection in allo-HSCT patients. Approximately 300 patients and their donors will be enrolled across several major transplant centers in China. Blood samples will be collected before and after transplantation to test for both HCMV-miRNA and HCMV-DNA. The study will compare the sensitivity and timing of miRNA detection with conventional DNA testing and explore whether miRNA can serve as an early biomarker of infection and related complications. The goal is to improve early diagnosis and management of HCMV infection, reduce infection-related complications, and ultimately improve survival outcomes in patients undergoing allo-HSCT.

Ruxolitinib Plus Etanercept vs Ruxolitinib for Steroid-Refractory Severe Acute GVHD

This is a prospective, multicenter, randomized controlled trial designed to evaluate whether the combination of ruxolitinib and etanercept provides superior efficacy compared with ruxolitinib monotherapy in patients with severe corticosteroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Acute graft-versus-host disease (aGVHD) is one of the most common and life-threatening complications following allo-HSCT. Although corticosteroids remain the standard first-line treatment, many patients do not respond adequately. For patients with severe steroid-refractory aGVHD, the prognosis is extremely poor, with high short-term mortality and very low long-term survival. Ruxolitinib, a JAK1/2 inhibitor, has been approved for the treatment of SR-aGVHD, but response rates remain suboptimal, particularly in patients with gastrointestinal involvement. Etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, has shown activity in GVHD by targeting inflammatory pathways. Previous observational studies from our center suggested that combining ruxolitinib with etanercept may improve response rates, especially in gastrointestinal and hepatic GVHD, without significantly increasing relapse risk. In this trial, approximately 122 patients with grade III-IV SR-aGVHD will be randomized 1:1 to receive either ruxolitinib alone or ruxolitinib plus etanercept. The primary endpoint is the overall response rate (ORR) at day 28. Secondary endpoints include durable response, best overall response, failure-free survival, overall survival, cumulative incidence of relapse, non-relapse mortality, incidence of chronic GVHD, and safety outcomes. This study seeks to provide new clinical evidence for an optimized treatment strategy for patients with severe SR-aGVHD, aiming to improve outcomes in this high-risk population.

Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure

Background: \- Some sickle cell disease or beta-thalassemia can be cured with transplant. Researchers want to test a variation of transplant that uses low dose radiation and a combination of immunosuppressive drugs. They want to know if it helps a body to better accept donor stem cells. Objectives: \- To see if low dose radiation (300 rads), oral cyclophosphamide, pentostatin, and sirolimus help a body to better accept donor stem cells. Eligibility: \- People 4 and older with beta-thalassemia or sickle cell disease that can be cured with transplant, and their donors. Design: * Participants and donors will be screened with medical history, physical exam, blood test, tissue and blood typing, and bone marrow sampling. They will visit a social worker. * Donors: * may receive an intravenous (IV) tube in their groin vein. * will receive a drug injection daily for 5 or 6 days to move the blood stem cells from the bone marrow into general blood circulation. * will undergo apheresis: an IV is put into a vein in each arm. Blood is taken from one arm, a machine removes the white blood cells that contain blood stem cells, and the rest is returned through the other arm. * Participants: * may undergo red cell exchange procedure. * will remain in the hospital for about 30 days. * will receive a large IV line that can stay in their body from transplant through recovery. * will receive a dose of radiation, and transplant related drugs by mouth or IV. * will receive blood stem cells over 8 hours by IV. * will take neuropsychological tests and may complete questionnaires throughout the transplant process. * must stay near NIH for 4 months. They will visit the outpatient clinic weekly.

Chimeric Natural Killer Receptor-Universal T Cells for Refractory GVHD

This is a single arm, open-label, multi-center, pilot studies (Investigator Initiated Trial, IIT) to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of universal T-cells engineered with chimeric natural killer receptor (CNK-UT) to treat the patients with steroid-refractory/resistant or steroid-dependent GVHD.