View clinical trials related to Graft vs Host Disease.
Filter by:The purpose of this study is to evaluate the safety and tolerability of topical tacrolimus 0.05% twice a day in the treatment of ocular graft versus host disease (GVHD). A secondary objective is to compare the efficacy of topical tacrolimus 0.05% drops compared with topical methylprednisolone sodium succinate 0.5% drops in patients with ocular GVHD. 40 patients with ocular GVHD who meet the inclusion criteria of the study as determined by a screening visit will be divided into two equal groups. In addition to their current medication, one group will receive the topical tacrolimus 0.05% drops and the other group will receive the topical methylprednisolone sodium succinate 0.5% drops. The participants will then have two follow-up visits at the week 5 and week 10 markers after their screening visit. To evaluate the purpose of the study as well as the patient's safety, the following procedures will be performed at each visit: a comprehensive eye examination, tear break-up time (TBUT), Schirmer's test, intraocular pressure (IOP), fundoscopy and grading scores of lid margin and corneal fluorescein staining. The following questionnaires will be administered at each visit: Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE). Impression cytology specimens will be taken only at the screening visit and at the week 10 visit.
Objective: A common, serious and debilitating long term complication of hematopoietic stem cell transplant (HCST) is chronic graft-versus-host disease (GVHD). Ocular GVHD develops in up to 85% of patients with chronic GVHD. It is characterized by progressive keratitis sicca and cicatrizing ocular inflammatory surface disease with T cell mediated damage to conjunctival and corneal epithelium and lacrimal tissue. Various medical and surgical treatments have been used, such as various lubricating agents, steroid drops and ointments, cyclosporin drops, punctal plugs or cautery and partial tarsorrhaphy. However, in severe cases, none offer acceptable, long-lasting relief from pain, irritation, dryness and diminished vision associated with ocular GVHD. An alternative treatment that has previously been safely investigated is autologous serum eye drops (ASEDs). The objective of this study is to determine whether ASEDs are more effective than control (normal saline) in the treatment of severe chronic ocular GVHD in HSCT patients unresponsive to standard medical treatment. Study Population: Eighteen post-HSCT patients with severe ocular GVHD unresponsive to standard medical treatment are enrolled. Initially, 34 post-HSCT patients with severe ocular GVHD unresponsive to standard medical treatment were to be enrolled. However, only 18 are enrolled, as the IP will no longer be provided to participants. Design: This is a Phase 2, randomized, double-masked, controlled, crossover, single-center study to investigate ASEDs in participants with severe chronic ocular GVHD. During the initial crossover phase of the study, participants participated in a two-period, six-month, crossover study in which participants were randomized to one of two treatment sequence groups. The two groups were: 1) daily administration of ASEDs for the first three months and then crossover to control (normal saline) eye drops beginning at Month 3 through Month 6, or 2) daily administration of control (normal saline) eye drops for the first three months and then crossover to ASEDs beginning at Month 3 through Month 6. Participants in both groups applied the assigned drops four times per day for six months, as well as maintain their current standard ocular GVHD therapy. Following the initial crossover phase, beginning at the Month 6 visit, participants were provided ASEDs as open-label treatment on an as-needed basis until study completion. The participants were informed to discontinue use of the IP and send it back the NIH Pharmacy. During the first year, required clinic visits occurred at Baseline, Months 3, 6 and 12 with required telephone follow-up visits at Months 7 and 9. Following the Month 12 visit, participants were evaluated every six months, alternating telephone follow-up visits with clinic visits, until the last enrolled participant reaches his/her Month 12 visit. All study participants will now be scheduled for a final safety visit. At the discretion of the Investigator, participants who have not completed the Month 12 visit may have the most recent study visit constitute as the final safety visit, otherwise the participant will be scheduled for a final safety visit within 4 1/2 months. Participants who have already surpassed the Month 12 visit will be scheduled for a final safety visit within 4 1/2 months. Outcome Measures: The primary outcome is the proportion of participants experiencing a greater than or equal to 50% reduction in the combined score of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in the study eye from baseline to Month 3. A greater than or equal to 50% reduction in the combined score will be considered a treatment success. While the design is a crossover study, the primary outcome is assessed after the first period at Month 3. Secondary outcomes include changes in the combined score of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in both eyes from baseline to the end of each period, changes in the chronic ocular GVHD Composite Assessment Scale (CAS) score, objective testing, subjective testing and global chronic GVHD assessments in both eyes. Safety outcomes will be the number and severity of systemic and ocular toxicities and adverse events. The number of participants withdrawn from the study treatment due to vision loss, adverse events or treatment failure will also contribute to the assessment of safety.
Graft versus Host Disease (GvHD), in both its acute and chronic forms, is the major intrinsic complication of allogeneic hematopoeitic stem cell transplant (allo-HSCT). Moreover, chronic GvHD may be regarded as a "late effect" of cancer therapy, and the severity of chronic GvHD is the chief determinant of long-term survival following allo-HSCT. Unfortunately, the investigators understanding (and thus management) of chronic GvHD is not optimal; a recent NIH Consensus Conference has defined inadequacies in virtually all facets of chronic GvHD management. Notably for this study, the lack of suitable biomarkers compromises diagnosis, staging and therapeutic response evaluation of chronic GvHD - and also hinders better understanding of the biology of this process. In particular, the activity of chronic GvHD is often difficult to discern, potentially causing either undertreatment, with the risk of morbidity and/or mortality due to uncontrolled chronic GvHD, or possibly overtreatment, with potent ISTs causing unnecessary toxicity. Obviously, the development of reliable biomarkers of chronic GvHD activity would be a very useful advance in addressing this problem, as well as other facets of management not addressed due to certain limitations, as detailed herein. Potentially, certain imaging technologies could address this problem. To date, imaging technology has been used only sporadically in chronic GvHD and is not an integral part of routine assessments. However, and despite its nonspecific nature, certain "inflammatory" features of some chronic GvHD cases, plus clinical similarity to certain autoimmune diseases in which functional imaging has been tested in research trials - (and perhaps notably), a limited experience in acute GvHD - the investigators postulate that Positron emission tomography - computed tomography (PET-CT) scans may be useful as a biomarker of disease activity in chronic GvHD. This protocol is an initial effort to that end.
The purpose of this study is to determine the safety and efficacy of sequential infusion of allogenic mesenchymal stem cells (MSC) expanded "in vitro" in treating patients with acute graft-versus-host disease refractory to first-line therapy.
The participant is invited to take part in this study because they have chronic Graft versus Host Disease (cGVHD) that is not responding to standard treatment with steroids. This research study is a way of gaining new knowledge about the treatment of patients with cGVHD. This research study is evaluating a drug called abatacept. Abatacept is a drug that alters and suppresses the immune system. Abatacept is approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe active rheumatoid arthritis in adults and of severe juvenile idiopathic arthritis (JIA) in patients who have failed prior therapy with disease-modifying anti-rheumatic drugs (DMARDs). These are autoimmune conditions, ie caused by an overactive immune system that attacks normal tissues and organs. It is currently being tested in a variety of other autoimmune conditions. In this case it is considered experimental. cGVHD is caused by the donor cells attacking various organs of the recipient. The investigators try to minimize this immune attack by using corticosteroids such as prednisone. In severe cases prednisone is not sufficient and other immunosuppressive medications are used in addition in order to more efficiently control cGVHD and to limit the dose and consequently the multiple side-effects of corticosteroids. This study is being done to determine if the use of abatacept is safe in patients with cGVHD and if it can facilitate a better control of cGVHD. During this study the participants will be evaluated for side effects from the treatment with abatacept, and for response of the cGVHD to the treatment. There will be two groups of participants in the study. The first group will be treated at a relatively low dose of abatacept. If this is found to be safe then the second group will be treated at a higher dose. Three to four tablespoons of blood will be drawn at every 2 week visit in order to determine your blood counts, kidney and liver function. Some of the blood will be used in a research lab in order to study measures of your immune system and how they might be affected by the treatment.
Background: The gastrointestinal (GI) tract is commonly affected by acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) in patients who have undergone blood or marrow stem cell transplantation (BMT). Initially, patients are treated with systemic corticosteroids, which produce complete response rates in 35 percent. Although short courses of steroids are preferred to minimize adverse effects, many patients require systemic treatment chronically since GI GVHD can negatively impact quality of life and nutrition status. One option to minimize systemic steroid exposure is by nonabsorbable corticosteroids that act locally on the GI tract. Budesonide (Entocort EC, AstraZeneca, Wilmington, DE) is an FDA-approved oral topical corticosteroid for the treatment of mild to moderate active Crohn s disease involving the ileum and/or the ascending colon, and for maintenance of clinical remission of mild to moderate Crohn s disease involving the ileum and/or the ascending colon for up to 3 months. It has a high ratio of topical-to-systemic activity with minimally active metabolites, and undergoes extensive first-pass metabolism. Since both intestinal GVHD and Crohn s disease seem to share a similar pathogenic background, budesonide has been used in the BMT setting for GI GVHD, usually in combination with systemic corticosteroids (e.g. methylprednisolone) to improve clinical response and allow for more rapid tapering of systemic corticosteroid doses. First-pass metabolism is mediated mostly by the cytochrome P450 (CYP450) enzyme system. The liver is the major site of CYP450-mediated metabolism but the enterocytes of the intestinal epithelium are also an important site for drug metabolism. Budesonide undergoes significant metabolism by CYP enzymes with substantial first-pass metabolism. The potential for greater systemic availability of orally administered budesonide exists when it is given concurrently with triazole antifungals, which are commonly prescribed for prophylaxis or treatment of fungal infections after transplantation. Fluconazole and voriconazole are moderate and strong inhibitors of CYP3A4, respectively, and budesonide is a CYP3A4 substrate. Inhibition of CYP3A4 may impair the metabolism of budesonide, resulting in systemic concentrations of budesonide and subsequently, adverse effects such as hyperglycemia. If the presence of fluconazole or voriconazole does impair budesonide s metabolism, then dose adjustments to budesonide may be warranted. There are no prospective studies evaluating the effects of fluconazole or voriconazole on budesonide s pharmacokinetics in patients who have undergone BMT. The primary objective of the proposed study is to determine the effects of fluconazole and voriconazole on the trough (Cmin) and peak (Cmax) of budesonide in patients who have undergone BMT and who have GI GVHD. The primary endpoints are the Cmin and Cmax of budesonide. Secondary endpoints include the Cmin of voriconazole. Objectives: The proposed study seeks to determine the effects of fluconazole and voriconazole on the Cminand Cmax of budesonide. Eligibility: Adult and pediatric subjects (greater than or equal to 13 years of age and greater than or equal to 49 kg) who are registered to an NCI or NHLBI protocol who have undergone a bone marrow, cord, haplo-cord or peripheral blood stem cell transplantation who have GI GVHD as determined by the medical team and who require treatment with budesonide and are candidates for antifungal therapy are eligible for this study. Design: Each subject will serve as his or her own control to minimize the variation in absorption, distribution, metabolism and elimination of oral budesonide that can occur from subject to subject, due to genetic, anatomic or other unidentified differences. For example, genetic polymorphisms of CYP2C19, which is significantly involved in voriconazole s metabolism, could otherwise affect the results of the study (i.e. CYP2C19 poor metabolizers may experience higher voriconazole serum concentrations, which could results in greater CYP3A4 inhibition and higher budesonide exposure). In addition, the longitudinal cohort design of this study will be able to answer the research questions posed with fewer research subjects. Research subjects will be accrued into one of three cohorts depending on the antifungal prophylaxis (or lack thereof) the subject is receiving at study entry and the preference of the medical team for continued antifungal coverage after the initiation of budesonide and systemic corticosteroids. Subjects who are not currently receiving antifungal prophylaxis or who are on fluconazole at baseline are eligible for enrollment in Cohort 1. Subjects in Cohorts 2 and 3 are receiving voriconazole and fluconazole at study entry, respectively. In Cohort 1, if applicable, subjects will stop fluconazole on day -1...
Infusion of Mesenchymal Stem Cell (MSC) at day of recovery after bone marrow transplant (BMT) for patients with AL, AA and MM for acute Graft-versus-host Disease (GVHD) prophylaxis and treatment.
This research study is trying to determine the safest dose of Brentuximab Vedotin that can be given to patients with chronic GVHD and see if chronic GVHD improves.
This research study is a Phase I clinical trial, which tests the safety of an investigational combination of IL-2 plus donor anti-inflammatory Treg cells and also tries to define the appropriate dose of the investigational combination of IL-2 plus donor anti-inflammatory Treg cells to use for further studies. IL-2 is involved with cell signaling and regulation of white blood cells (WBCs). WBCs are part of the immune system. Treg cells are also part of the immune system; they are involved with anti-inflammatory responses. "Investigational" means that the combination of IL-2 and anti-inflammatory Treg cell infusion is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved the combination of IL-2 and anti-inflammatory Treg cell infusion for use in people with cGVHD. Chronic GVHD is a medical condition that may occur after you have received your bone marrow, stem cell or cord blood transplant from a donor. The donor's immune system may recognize your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host disease. Traditional standard therapy to treat cGVHD is prednisone (steroids). Participants on this trial have not responded to steroid therapy. The investigators are looking to assess the safety and optimal dose for the combination of IL-2 plus donor anti-inflammatory Treg cells, that may help control cGVHD by stopping the donor's immune system from 'rejecting' your body.
IL-2 add-back post allogeneic hematopoietic stem cell transplant (HSCT), combined with Sirolimus (SIR), Tacrolimus (TAC) will optimize Treg reconstitution and prevent graft versus host disease (GVHD).