291 Clinical Trials for Various Conditions
The goal of this research proposal is to identify a miRNA expression profile as a biomarker to diagnose and predict acute graft versus host disease (aGVHD) in patients who undergo allogeneic transplantation. This biomarker, once identified, will need validation in larger cohorts.
Acute Graft Versus Host Disease (GVHD) is a serious medical condition that is a common development after Bone Marrow Transplant (BMT). Acute GVHD happens when the donor cells attack and damage your tissues and organs after transplant. Acute GVHD often causes: Skin rashes, nausea, vomiting, abdominal pain, diarrhea (may have blood), liver damage that can cause inflammation in the liver or jaundice (yellowing of the skin or eyes), damage to other organs Steroids are the first line of treatment for acute GVHD. About a quarter of the patients that develop acute GVHD may not respond to steroid and have steroid refractory GVHD (SR-aGVHD). Patients with SR-aGVHD may need other medications. SR-aGVHD, is a potentially life threatening condition. There is no standard treatment and it may not respond to treatment. The goals of this study are to find out if Infliximab and basiliximab can treat SR-aGVHD. Participants in this study will receive combination therapy (2 drugs: infliximab and basiliximab) once a week for four weeks.
Acute graft versus host disease (GVHD) remains one of the most significant and potentially lethal complications of allogeneic bone marrow transplantation. Depending upon the type of transplant, the incidence of acute GVHD varies between 20 - 50% in related donor transplants, or as high as 70 - 90% in unrelated donor transplants. Acute GVHD affects the skin, liver and gastrointestinal (GI) tract and usually occurs within 20 - 40 days of the bone marrow infusion. Steroids are the standard initial treatment of acute GVHD, with approximately 50% of the patients either free of disease or requiring no further therapy. In the remaining patients, the GVHD either does not respond or it comes back during the tapering of steroids. These patients have a much worse prognosis with a mortality rate greater than 70%. Studies using additional agents such as antithymocyte globulin (ATG), monoclonal antibodies, and anti-lymphocyte globulin showed no improvement over the use of steroids alone. This leads the investigators to look for new immunosuppressive agents that can reduce the risk and severity of acute GVHD. The major purpose of this study is to evaluate the way the body uses and absorbs (the pharmacokinetic profile) a drug called anti tumor necrosis factor antibody (infliximab) for the treatment of acute GVHD. Infliximab is currently indicated for the treatment of immunologic-based diseases (rheumatoid arthritis, moderately to severely active Crohn's disease, and fistulizing Crohn's disease), assuming patients have had inadequate responses to conventional therapy. It is not approved for the treatment of GVHD. This is a Phase I pharmacokinetic study that is coordinated by the Pediatric Blood and Marrow Transplant Consortium (PBMTC). The study will be conducted in the Blood and Marrow Transplantation (BMT) program at Children's Healthcare of Atlanta - Egleston, Emory University Department of Pediatrics. The goal is to enroll 1 - 2 patients on this study; accrual will be via the BMT program. Eligible patients must be less than 18 years of age. Patients with newly diagnosed acute GVHD will be able to participate in the study. Patients will receive a single dose of infliximab in the clinic. Since this is a Phase I study, the patients will have blood samples drawn to measure the pharmacokinetics of the drug. A total of 16 blood samples will be drawn over 84 days. The samples will be labeled with a code, processed, frozen, and then sent in a batch to the PBMTC designated laboratory for testing. Patients will continue on any drugs they were getting for the prevention of GVHD. Additional doses of infliximab may be given. This decision will be based on the results of the blood testing.
This study is a Open Label Prospective Dose-Ranging Escalation and Expansion Trial to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the secondary treatment of acute Graft-versus-Host Disease (aGvHD) in hospitalized patients who are steroid-refractory.
The purpose of this study is to test whether the combination of the drugs called tacrolimus (Tac), methotrexate (MTX) and new dosing strategy of another drug called (rabbit Anti-thymocyte Globulin \[ATG\]) will help prevent the development and/or improve severity of acute and/or chronic GVHD.
In an effort to reduce graft versus host disease (GVHD) and enhance graft versus leukemia (GVL) effect post allogenic hematopoietic stem cell transplantation (AHSCT), recent research has focused on host immune cell depletion. Frame shifting anti-thymocyte globulin (ATG) backwards to earlier days before days 0 can result in deeper host and less graft T-cell depletion, leading to better immune reconstitution. Preliminary data where 80% of the ATG dose is given on days -6,-5,-4 and 20% given on day -1, showed effective prevention of severe acute GVHD, chronic GVHD and favorable early immune reconstitution. We hypothesize that our 2 step ATG dosing platform when combined with standard tacrolimus and mini methotrexate can prevent grade III-IV acute GVHD and chronic GVHD, resulting in improvement of GVHD/relapse free survival at one year post transplant.
This randomized placebo-controlled double-blind phase II trial tests whether fecal microorganism (microbiota) transplantation prevents severe acute graft versus host disease in adults undergoing allogeneic hematopoietic cell transplantation (HCT). Fecal microbiota transplantation involves receiving processed fecal material orally after allogeneic HCT in order to establish a healthy gut microbiota. Gut microbiota undergoes major alterations during allogeneic HCT because of antibiotic exposures, nutritional changes, and chemotherapy administration. Establishing a healthy gut microbiota via fecal transplantation may help prevent acute graft versus host disease in patients undergoing allogeneic HCT.
The prediction of severe acute GVHD before it occurs is of high importance for ensuing clinical decisions and overall success of allogeneic SCT. The key immunologic signatures associated with clinical outcomes after different graft versus host disease prophylaxis methods or peripheral blood stem cell transplant are largely unknown.
The primary purpose of the study is to assess the safety and pharmacokinetics (PK) of GDC-8264 in participants with acute graft-versus-host disease (aGVHD).
This phase I trial tests the safety and side effects of leflunomide in combination with steroids in treating patients with acute graft versus host disease who have undergone done stem cell transplant for blood cancers (hematologic malignancies). Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Leflunomide and steroids are immunosuppressive drugs that work in different ways to lower the body's immune response so that the new donor immune cells do not attack the body's normal cells. Giving leflunomide in combination with steroids may help treat acute graft versus host disease in patients after stem cell transplant for hematologic malignancies.
This is a multi-center study to compare the efficacy and safety of itolizumab versus placebo as first-line therapy for subjects with Grade III-IV aGVHD or Grade II with LGI involvement, in combination with corticosteroids
This is an open-label, randomized, Phase 3, multicenter trial, which has been designed to compare the efficacy and safety of T-Guard to ruxolitinib in patients with Grade III or IV Steroid-Refractory acute Graft-Versus-Host Disease (SR-aGVHD). The primary hypothesis is that T-Guard treatment will improve the Day 28 complete response (CR) rate in patients with Grades III and IV SR-aGVHD compared to ruxolitinib.
This phase Ib/II trial studies the side effects of PLX51107 in treating steroid-refractory acute graft versus host disease (GVHD). PLX51107 is a novel, potent non-benzodiazepine structured small molecule BET inhibitor with a unique binding mode selective for BRD4 inhibition and a more tolerable side effect profile. PLX51107 may work better in treating steroid-refractory acute GVHD.
This early phase I trial is to find out the effect of adding cord blood tissue-derived mesenchymal stromal cells (cb-MSCs) to ruxolitinib in treating patients with acute graft versus host disease that does not respond to steroid therapy (steroid-refractory). Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. cb-MSCs are a type of tissue helper cell that can be removed from donated umbilical cord blood tissue and grown into many different cell types that can be used to treat cancer and other disease, such as graft versus host disease. This trial aims to learn if adding cb-MSCs to ruxolitinib may help control steroid-refractory acute graft versus host disease.
This phase II trial studies how well ustekinumab works in preventing acute graft-versus-host disease after unrelated donor hematopoietic cell transplant. Sometimes the transplanted cells from a donor can attack the body's normal tissues (called graft-versus-host disease). Giving ustekinumab after the transplant may help prevent acute graft-versus-host disease by controlling the body's immune response. Funding Source- FDA OOPD.
The Balance study will assess the safety, tolerability, and efficacy of an investigational drug called ALPN-101 in adults with steroid-resistant or steroid-refractory acute graft versus host disease (aGVHD).
This is a single-center Phase I study to determine the maximum tolerated dose and safety of Neihulizumab for the treatment of Minnesota standard-risk aGVHD. Patients undergoing allogeneic transplant with either a myeloablative or non-myeloablative conditioning regimen, and recipients of all donor sources will be enrolled to this trial.
The purpose of this study is to evaluate the effectiveness of Fecal Microbiota Transplant (FMT) treatment in high-risk acute graft-versus-host disease (GVHD). This research study involves an experimental intervention called FMT.
The study is designed as an open-label, single arm Phase III, multicenter trial to evaluate the efficacy and safety of T-Guard treatment in patients with Steroid-Refractory acute Graft versus Host Disease (SR-aGVHD).
This is a phase 2 open-label trial designed to evaluate the efficacy of tildrakizumab in improving graft-versus-host disease (GVHD)-free relapse-free survival after myeloablative allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy.
The study compares two acute graft-versus-host disease (aGVHD) prophylaxis regimens: efprezimod alfa vs placebo with the standard GVHD prophylaxis of tacrolimus / methotrexate. The study compares two acute graft-versus-host disease (aGVHD) prophylaxis regimens: efprezimod alfa/tacrolimus / methotrexate (efprezimod alfa/Tac/MTX) versus placebo/tacrolimus / methotrexate (placebo/Tac/MTX) in the setting of myeloablative conditioning (MAC), matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation in participants with acute leukemia (AML/ALL) or myelodysplastic syndrome (MDS). The study agent, efprezimod alfa, will be administered through IV infusion on days -1, 14, and 28 at the dose of 480mg, 240 mg and 240mg, respectively. The placebo will be 100 ml normal saline intravenous (IV) solution.
The study's primary objective is designed to assess the safety and tolerability, and determine the maximum tolerated dose (MTD) of both itacitinib and tocilizumab when given in combination to patients with steroid-refractory acute graft versus host disease (SR-aGVHD). The study's secondary objectives are to: * Estimate the day 28 response rate (ORR) \[complete response (CR), very good partial response (VGPR), and partial response (PR)\] of the combination of itacitinib and tocilizumab for the treatment of SR-aGVHD * Estimate the time to response and duration of response * Estimate the incidence of primary disease relapse while on study treatment * Estimate the incidence of infections including viral reactivation, bacterial infections and fungal infections while on study treatment * Estimate the progression-free survival (PFS), overall survival (OS), non-relapse mortality, GVHD-related mortality of study subjects * Estimate the proportion of patients who successfully discontinue steroids by 6 months and 12 months after therapy initiation
Gastro-Intestinal Acute Graft Versus Host Disease (GI-aGVHD) is a complication of allogeneic stem cell transplant which is usually treated with steroids. You are being asked to take part in this study because you have recently been diagnosed with GI-GVHD. The standard of care for GI-aGVHD is steroids. When aGVHD does not respond to steroids it is described as steroid-refractory aGVHD. There is no standard therapy for steroid-refractory GI-aGVHD. This study is a Phase II study. The main goal of a Phase II study is to see the efficacy and what side effects are seen with FMT as a treatment for GVHD. Fecal Microbiota Transplantation (FMT) is the transfer of fecal material from a healthy donor to a patient in order to restore the diversity of the intestinal microbiota. FMT is currently indicated for the treatment of recurrent Clostridium Difficile infection. FMT is considered experimental in this study, meaning it is not approved by the FDA for the treatment of GVHD.
This Phase II open label study will evaluate the safety and efficacy of repeat doses of RGI-2001 in combination with standard of care treatment for the prevention of acute graft-vs-host-disease (aGvHD) in subjects following Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT). These subjects will be compared to contemporary controls.
Finding a donor remains a challenge for patients in need of an urgent hematopoietic stem cell transplantation (HSCT). The ability to obtain half matched stem cells from any family member represents a significant breakthrough in the field. Haploidentical haplo-HSCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post-transplant cellular immunotherapy. However, haplo-HSCT has a high risk of Graft versus Host Disease (GvHD) and poor immune reconstitution when GvHD is prevented by all existing methods of vigorous ex vivo or in vivo T-cell depletion. Different treatment approaches are currently being explored to mitigate complications such as graft rejection, severe GvHD, and prolonged immune suppression. Novel experimental utilization of T regulatory cells, alloreactive natural killer (NK) cells, and other T cell subsets hold great promise. Cellect Biotherapeutics' platform technology, ApoGraft, is based on the findings that GvHD can be prevented by Fas receptor mediated selective depletion of T cell subsets, ex vivo. The investigators hypothesize that the use of ApoGrafts for haplo-HSCT will be safe, and reduce rates of GVHD without affecting Graft-versus-Leukemia (GvL).
This trial will see if extended abatacept administration (combined with a standard regimen of tacrolimus and mycophenolate mofetil) will prevent acute and chronic graft-versus-host disease (GVHD) in children and adolescents receiving unrelated donor (URD) hematopoietic stem cell transplantation (HSCT), without compromising their engraftment or reconstitution of protective immunity to infection. The study will enroll 30 pediatric patients with serious non-malignant hematologic diseases (NMHD) undergoing URD HSCT. The trial will include patients with 7/8 donors and those with 8/8 (matched) donors. All participants will receive 8 doses of abatacept. Recruitment is expected to last for about 2 years and participants will be followed for up to 3 years.
This phase II trial studies how well a fecal microbiota transplant with or without total gut decontamination works in preventing graft versus host disease in patients exposed to broad-spectrum antibiotics. Fecal microbiota transplantation is the administration by enema of fecal matter (stool) that includes helpful bacteria from a normal, healthy donor. Total gut decontamination uses antibiotics to remove/reduce the amount of bacteria in the digestive system. It is not yet known if a fecal microbiota transplant with or without total gut decontamination works better in preventing graft versus host disease compared to standard immunosuppressive therapies (therapies that lower the normal function of the immune system).
The purpose of this study is to evaluate the efficacy of vedolizumab when added to background aGvHD prophylaxis regimen compared to placebo and background aGvHD prophylaxis regimen on intestinal aGvHD-free survival by Day +180 in participants who receive allo-HSCT as treatment for a hematologic malignancy or myeloproliferative disorder.
The purpose of this study is to examine the safety and efficacy of the addition of BMS-986004 to standard of care Sirolimus (SIR)-based immune suppression.
Bone marrow transplant (BMT) patients can develop graft-versus-host disease (GVHD), a serious and potentially fatal complication. The researchers have developed a blood test to identify patients most at risk for developing severe GVHD. Patients who consent to this study will have their blood tested up to two times after BMT to determine if they are at high risk for severe GVHD. The tests will be performed one week and two weeks after BMT. Patients who are high risk will be treated with a drug called alpha-1-antitrypsin (AAT) to see if it prevents the development of severe GVHD. Patients will receive 16 doses of AAT through a catheter placed into a blood vessel over eight weeks. AAT will be given either in the hospital or the outpatient clinic two times per week. Patients will be followed for the development of severe GVHD for up to four months from the BMT and will continue to be followed at routine clinic visits for up to one year after BMT.