Leflunomide + Steroids for Graft-versus-Host Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: City of Hope Medical Center
Must be taking: Steroids
Must not be taking: Investigational agents
Disqualifiers: Multiple HCT, Uncontrolled illness, HIV, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use other drugs for treating acute graft-versus-host disease during the study. It's best to discuss your current medications with the study team to see if they are allowed.
What data supports the effectiveness of the drug Leflunomide for treating graft-versus-host disease?
Research in rats has shown that Leflunomide can effectively prevent and treat graft-versus-host disease, a serious condition that can occur after a transplant. This suggests it might be useful in human cases as well.
12345Is the combination of Leflunomide and Steroids safe for treating Graft-versus-Host Disease?
The safety of steroids, including budesonide, for treating Graft-versus-Host Disease (GVHD) has been studied, showing a satisfactory safety profile with no severe intestinal infections reported. However, specific safety data for the combination of Leflunomide and steroids in GVHD is not provided in the available research.
678910How is the drug Leflunomide + Steroids unique for treating graft-versus-host disease?
Leflunomide, combined with steroids, is unique for treating graft-versus-host disease because it is an immunomodulating drug that has shown promise in preventing and treating this condition in animal models, and it has a background of being effective in autoimmune diseases and transplantation reactions. Its ability to work in synergy with other immunosuppressive agents and its lower toxicity compared to some alternatives make it a novel option for this condition.
134511Eligibility Criteria
Adults (18+) who've had a stem cell transplant for blood cancer and are now facing acute graft-versus-host disease can join. They must be able to take oral meds, have no severe organ issues unrelated to the disease, not be on dialysis or have uncontrolled infections, and agree to birth control if applicable. Prior leflunomide use or more than 72 hours of steroids for this condition disqualifies them.Inclusion Criteria
I am capable of having children and have not been surgically sterilized.
I have only used prednisone for acute GvHD for less than 72 hours.
Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
+17 more
Exclusion Criteria
I have received more than one bone marrow transplant from a donor.
I haven't had cancer other than my current one in the last 3 years.
I do not have severe organ problems not caused by GvHD.
+23 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive steroid therapy and leflunomide orally once daily on days 1-28, with tapering from day 29 to day 56 if responsive
8 weeks
Weekly visits for monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
Follow-up visits at 28 days, 56 days, 100 days, and 6 months
Participant Groups
The trial is testing the safety of combining leflunomide with steroids in treating acute graft-versus-host disease post-stem cell transplant. It's seeing if this combo helps manage immune responses better so that donor cells don't attack the patient's body.
1Treatment groups
Experimental Treatment
Group I: Treatment of aGVHD (steroid therapy, leflunomide)Experimental Treatment3 Interventions
Patients receive steroid therapy at the discretion of the treating physician. Beginning within 3 days of starting steroids, patients receive leflunomide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients who respond to leflunomide treatment will be tapered off from day 29 until day 56.
Leflunomide is already approved in European Union, United States, United Kingdom for the following indications:
🇪🇺 Approved in European Union as Arava for:
- Rheumatoid arthritis
- Psoriatic arthritis
🇺🇸 Approved in United States as Arava for:
- Rheumatoid arthritis
- Psoriatic arthritis
🇬🇧 Approved in United Kingdom as Arava for:
- Rheumatoid arthritis
- Psoriatic arthritis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Experiences with leflunomide in solid organ transplantation. [2022]Leflunomide (Arava), a drug widely used for treatment of rheumatoid arthritis, has a very promising background in experimental transplantation. Its activity in experimental models of chronic rejection, its synergy with calcineurin phosphatase inhibitors, and its inhibitory effects on herpes virus replication are compelling reasons to pursue its clinical evaluation in transplantation. We report the use of this drug over the past 3 years in various clinical situations.
[Lichenoid drug reaction to leflunomide]. [2018]Leflunomide (Arava) is an immunomodulator, recently introduced for systemic treatment of rheumatoid arthritis. We report the first case of lichenoid drug reaction due to this drug.
Prevention of the acute graft-versus-host disease (GVHD) in rats by the immunomodulating drug leflunomide. [2019]The grafting of immunocompetent allogeneic cells into MHC-discordant, genetically nonresponsive F1 hybrids of inbred rat strains consistently leads to an acute, lethal graft-versus-host disease (GVHD). The novel immunomodulating drug leflunomide, which has been shown to be efficacious in animal models of autoimmunity and adverse transplantation reactions, was studied in a rat model of GVHD. It was found that this drug not only was a powerful agent to prevent this otherwise terminal disorder, but was also proficient when used as a therapy of an established GVHD. Since leflunomide has been shown to be efficacious and safe in patients with chronic rheumatoid arthritis, it would also be reasonable to investigate this drug in clinical trials for bone marrow transplantation and GVHD in human beings.
Leflunomide for chronic sarcoidosis. [2019]Leflunomide (Arava) is a cytotoxic drug which has been used as a single agent or in combination with methotrexate for the treatment of rheumatoid arthritis. It appears to have less toxicity than methotrexate. The use of leflunomide for sarcoidosis patients has not been systematically evaluated.
Effects of a short course of leflunomide on T-independent B-lymphocyte xenoreactivity and on susceptibility of xenografts to acute or chronic rejection. [2019]Leflunomide is a novel immunosuppressive agent with promising activity for xenotransplantation. It is not clear yet which mechanisms of action of leflunomide are responsible for that.
Feasibility and response to budesonide as topical corticosteroid therapy for acute intestinal GVHD. [2022]Therapy of acute intestinal GVHD is still one of the main challenges after allogeneic transplantation. Increasing systemic immunosuppression (IS) is the first choice and includes corticosteroids and lymphocyte antibodies, often associated with severe side-effects. In inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, topical steroid therapy is used very successfully. Because of the similarity between these and acute intestinal GVHD we conducted a trial with oral budesonide (Budenofalk), a new topically active glucocorticoid, to treat patients with acute GVHD > or = grade II. After a diagnosis of aGVHD > or = grade II, 22 patients received increased IS, mainly systemic corticosteroids, and additionally budesonide 9 mg/day divided into three doses. Improvement in aGVHD, infectious side-effects, reduction of systemic IS and outcome were documented. Results were compared with the results of 19 control patients, who were treated only by increasing IS dose. In 17/22 patients (70%), treated with budesonide, the acute intestinal GVHD resolved and no relapse occurred after decreasing the systemic IS, while continuing budesonide. In only 8/19 patients in the control group did the acute intestinal GVHD resolve and 2/8 patients had a relapse of intestinal GVHD after decreasing IS, with an overall response of 33%. No severe intestinal infections occurred. We conclude that budesonide may be effective in acute intestinal GVHD as a topical corticosteroid and prospective, randomized studies should demonstrate its efficacy in allowing reduction of systemic immunosuppressive therapy, and its side-effects.
A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease. [2022]To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD).
Budesonide: a novel treatment for oral chronic graft versus host disease. [2004]This clinical trial aims to evaluate the efficacy of budesonide, a newly registered steroid with high potency and low bioavailability, for the treatment of chronic oral graft versus host disease (GVHD).
Comparison of budesonide and dexamethasone for local treatment of oral chronic graft-versus-host disease. [2019]The results of a prospective study of topical budesonide versus topical dexamethasone therapy for oral manifestations of chronic graft-versus-host disease (cGVHD) are presented.
Topical Corticosteroids a Viable Solution for Oral Graft Versus Host Disease? A Systematic Insight on Randomized Clinical Trials. [2021]Background and Objectives: This research attempts to provide a clear view of the literature on randomized clinical trials (RCTs) concerning the efficacy of topical dexamethasone, clobetasol and budesonide in oral graft versus host disease (GVHD). Materials and Methods: An electronic search of the PubMed, Web of Science and Scopus databases was carried out for eligible RCTs. Studies were included if they had adult patients with oral GVHD treatment with topical corticosteroids, and if the RCT study was published in English. The Cochrane Risk of Bias tool was used to assess the quality of these studies. Overall, three RCTs were included (an Open, Randomized, Multicenter Trial; a Randomized Double-Blind Clinical Trial; and an Open-Label Phase II Randomized Trial). Results: The trials involved 76 patients, of which 44 patients received topical dexamethasone, 14 patients received topical clobetasol and 18 patients received topical budesonide. Topical agents were most frequently used when oral tissues were the sole site of involvement. It appears that the best overall response is present for budesonide with no difference between the four arms, followed by clobetasol, and then by dexamethasone. The limitation of the current study is mainly represented by the fact that overall response was derived in two of the studies from other parameters. Moreover, both budesonide and clobetasol were used in only one study each, while two assessed dexamethasone. Conclusions: Based on the clinical trials, all three agents seem to be effective in treating oral GVHD and had a satisfactory safety profile. There is still a need for assessing high quality RCTs to assess the efficacy of these therapies on a larger cohort.
The effects of leflunomide on CD4(+)CD25 (+)Foxp3 (+) T regulatory cells in mice receiving allogeneic bone marrow transplantation. [2021]Leflunomide (LEF) is effective not only in different animal models of autoimmune diseases and the therapy of patients with rheumatoid arthritisbut also in graft rejection. The effect of LEF on CD4(+)CD25(+)T regulatory cells (Treg) was determined in a mouse model of allogeneic bone marrow transplantation.