Ruxolitinib vs Prednisone 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 2
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Allogeneic transplant is potentially curative for hematological malignancies but its use is limited by the development of GVHD. Ruxolitinib now has FDA approval for treatment of chronic GVHD that has failed 1-2 prior lines of therapy based on a prior large, randomized phase III study. Given this evidence of safety and efficacy in the early refractory setting (after prednisone failure), Ruxolitinib represents an ideal agent to test in the primary therapy setting. Here investigators propose a phase 2 randomized study to compare Ruxolitinib to prednisone as a first-line therapy in the treatment of chronic GVHD.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, no new immune suppressive therapy should be added within two weeks before joining the study.
What data supports the effectiveness of the drug Ruxolitinib for treating graft-versus-host disease?
Ruxolitinib has shown effectiveness in treating chronic graft-versus-host disease (GVHD), especially in patients who do not respond to steroids. Studies have reported high response rates, with many patients experiencing significant improvement and being able to reduce or stop steroid use.
12345Is Ruxolitinib safe for treating graft-versus-host disease?
Ruxolitinib has been shown to be generally safe for treating steroid-refractory graft-versus-host disease, with some patients experiencing side effects that were mostly manageable by adjusting the dosage. Common side effects were related to blood health, but they typically improved with treatment changes.
13567What makes the drug Ruxolitinib unique for treating graft-versus-host disease?
Ruxolitinib is unique because it is an oral medication that specifically inhibits JAK1/2 enzymes, which are involved in the immune response, making it effective for steroid-refractory graft-versus-host disease (SR-GVHD) where other treatments fail. It has shown high response rates but also carries a risk of viral reactivation, which is a consideration in its use.
468910Eligibility Criteria
This trial is for individuals with chronic graft-versus-host disease (GVHD) after an allogeneic transplant. Participants should need systemic therapy but haven't yet been treated, or their condition didn't improve with initial treatments.Inclusion Criteria
I am 18 years old or older.
I can care for myself but may need occasional help.
My blood counts and kidney function are within the required ranges.
Exclusion Criteria
I do not have active hepatitis B, C, or HIV.
I am not pregnant or breastfeeding.
I have or had active Tuberculosis.
I do not have serious or unmanaged heart problems.
My cancer has returned after a transplant.
I have been treated with immune suppressive therapy for chronic GVHD.
I do not have any infections that aren't under control.
Participant Groups
The study compares Ruxolitinib to Prednisone as a first-line treatment for chronic GVHD. It's a phase 2 randomized trial where participants are randomly assigned to receive either Ruxolitinib or Prednisone to evaluate effectiveness and safety.
2Treatment groups
Experimental Treatment
Active Control
Group I: Ruxolitinib Treatment ArmExperimental Treatment1 Intervention
Ruxolitinib is administered as 10 mg orally twice daily in 28-day cycles.
Group II: Prednisone Treatment ArmActive Control1 Intervention
Prednisone will be started at 1mg/kg/day based on patient current body weight in kilograms.
Prednisone is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Prednisone for:
- Allergic reactions
- Asthma
- Blood disorders
- Cancer
- Eye problems
- Immune system disorders
- Inflammatory conditions
- Multiple sclerosis
- Organ transplantation
- Rheumatoid arthritis
- Skin conditions
🇪🇺 Approved in European Union as Prednisone for:
- Allergic reactions
- Asthma
- Blood disorders
- Cancer
- Eye problems
- Immune system disorders
- Inflammatory conditions
- Multiple sclerosis
- Organ transplantation
- Rheumatoid arthritis
- Skin conditions
🇨🇦 Approved in Canada as Prednisone for:
- Allergic reactions
- Asthma
- Blood disorders
- Cancer
- Eye problems
- Immune system disorders
- Inflammatory conditions
- Multiple sclerosis
- Organ transplantation
- Rheumatoid arthritis
- Skin conditions
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who is running the clinical trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
Incyte CorporationIndustry Sponsor
References
Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease. [2023]Patients with steroid-refractory acute graft-versus-host disease (aGvHD) not tolerating/responding to ruxolitinib (RR-aGvHD) have a dismal prognosis.
Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease. [2021]Inhibition of the Janus-associated kinases (JAK) with ruxolitinib (RUX) reduces graft-versus-host disease (GVHD) in preclinical and clinical models. In total 19 allograft recipients with moderate/severe steroid-dependent chronic GVHD received RUX as ≥2nd line salvage. RUX was well tolerated, and led to complete/partial resolution of oral (92/7%), cutaneous (82/0%), hepatic (71/28%), gastro-intestinal (75/17%), musculoskeletal (33/67%), pulmonary (0/80%), scleroderma (0/75%), vaginal (0/75%), and ocular (0/100%) chronic GVHD. Overall 18 achieved partial response and 1 complete response according to NIH Consensus Criteria. Responses occurred early and were sustained which enabled discontinuation (68%) or reduction of steroids to physiologic doses (21%). We conclude that RUX is an effective steroid-sparing agent in chronic GVHD.
A Multicenter, Retrospective Study Evaluating Clinical Outcomes of Ruxolitinib Therapy In Heavily Pretreated Chronic GVHD Patients With Steroid Failure. [2023]Although ruxolitinib is emerging as the treatment of choice for steroid-refractory or -dependent chronic graft versus host disease (cGVHD) based on randomized control trial data, there is relatively little real-world data published on ruxolitinib for this indication. We wanted to evaluate the real-world efficacy and safety of ruxolitinib in cGVHD patients who have failed any previous systemic therapy for cGVHD. We retrospectively evaluated the efficacy of ruxolitinib in 115 heavily pretreated patients with steroid-refractory or -dependent chronic GVHD across 5 transplantation centers. The majority of the study population had severe cGVHD (60%) and received ruxolitinib at the fourth treatment line or beyond (82%, n = 96). The median duration of follow-up in this study population was 13 months. The overall response rate (ORR) was 48.6%, 54.9%, and 48.5% at 3, 6, and 12 months, respectively. Clinical benefit (an outcome metric combining ORR with steroid reduction) was observed in 58.7%, 64.8%, and 60.6% of patients at 3, 6, and 12 months, respectively. Approximately one third of patients (37.9%) were able to discontinue prednisone at 12 months, and 63.8% were able to taper prednisone to a daily dose
Ruxolitinib-induced reactivation of cytomegalovirus and Epstein-Barr virus in graft-versus-host disease. [2023]Steroid-refractory graft-versus-host disease (SR-GVHD) is a challenging complication of allogeneic hematopoietic stem cell transplantation, and leads to high morbidity and mortality rates. The orally administered, selective Janus-associated kinase 1/2 inhibitor ruxolitinib gives overall response rates (ORR) of more than 70 % in acute and chronic SR-GVHD. However, several studies have highlighted an elevated risk of cytomegalovirus (CMV) reactivation in patients with ruxolitinib-treated SR-GVHD.
Long-Term Follow-Up of Ruxolitinib in the Treatment of Steroid-Refractory Chronic Graft-versus-Host Disease. [2021]Chronic graft-versus-host disease (cGVHD) remains a major barrier to successful hematopoietic stem cell transplantation (HSCT). In cases refractory to first-line therapy with steroids, there is no standard of care for second-line therapy. As such, ruxolitinib is a promising drug in this scenario. We retrospectively analyzed the efficacy and safety of ruxolitinib in treating steroid-refractory cGVHD in 35 patients from 2 transplantation centers, with the longest follow-up described to date. The evaluated patients had a median of 3 organs affected (range, 1 to 7 organs), with most (64%) having moderate cGVHD. The median number of previous therapy lines was 2 (range, 1 to 6). The overall response rate was 89% (complete response, 26%) after a median of 4 weeks of therapy. The median follow-up was 43 months (range, 11 to 59 monts). At follow-up, of the 27 patients still alive, 18 (67%) were free of any immunosuppression, and 6 (22%) were receiving ruxolitinib as their sole immunosuppressive drug. Failure-free survival was 77.1% at 6 months, 68.6% at 12 months, 54% at 24 months, and 51.4% at 36 months. The median overall survival was not reached. Toxicities were mostly hematologic and resolved after dosage reduction in most cases. Overall, our data, which represent the cohort of patients with cGVHD treated with ruxolitinib with the longest follow-up to date, support the use of this drug as a safe and effective option for refractory cGVHD.
Ruxolitinib add-on therapy in steroid-refractory graft-vs-host disease following hematopoietic cell transplantation: A single institutional experience. [2023]Steroid-refractory graft-vs-host disease (SR-GVHD) remains a significant cause of mortality after allogeneic hematopoietic cell transplantation (HCT), and the trajectory of treatment response for that vary. In our case series, we introduced six cases experiencing SR-GVHD who achieved better disease control after applying ruxolitinib (RUX). Of the six cases, five of them achieved symptoms-free while one of them, unfortunately, died of invasive fungal infection. Three alive cases were weaned off the RUX treatment successfully, while the remaining were on a medication tapering program. We demonstrated mixed efficacy in patients with SR-GVHD, suggesting that the RUX add-on may be a useful therapeutic adjunct in combination with other immunosuppressants.
Role of Ruxolitinib in Steroid-Refractory Graft versus Host Disease in Patients Undergoing Allogeneic Stem Cell Transplant. [2022]The objective of this study was to evaluate the role of Ruxolitinib in steroid-refractory graft versus host disease. This retrospective descriptive study was conducted from January 2018 to December 2021. A total of 157 patients underwent allogeneic stem cell transplants during the study period. Of these, 20 patients having steroid-refractory GVHD treated with Ruxolitinib were selected for the study. The primary endpoint was the overall response rate to Ruxolitinib measured at 4 weeks and 24 weeks for acute and chronic GVHD, respectively. The secondary endpoints were overall survival and failure-free survival. Of these 20 patients, 7 (35%) had acute GVHD, and 13 (65%) had chronic GVHD. Of acute GVHD, 2 (10%) had grade II, 4 (20%) had grade III, and 1 (5%) had grade IV acute GVHD. Of 13 patients with chronic GVHD, 7 (35%) had moderate and 6 (30%) had severe chronic GVHD. In steroid-refractory acute GVHD, the overall response rate to Ruxolitinib was 85.7%, and in chronic GVHD, it was 84.6%. The failure-free survival was 80% and overall survival was 85%. Adverse events of any grade occurred in 16 (80%) patients with grade III/IV adverse events in 4 (20%) patients only. The study showed that Ruxolitinib is a safe and effective second-line therapy for acute and chronic steroid-refractory GVHD. Key Words: Ruxolitinib, GVHD, Allogeneic stem cell transplant.
Ruxolitinib Treatment of Steroid-Refractory Graft-versus-Host Disease in Children: A Case Series and Review of the Literature. [2023]Ruxolitinib has been increasingly used in the treatment of steroid-refractory graft-versus-host disease (SR-GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. However, there are limited data on the use of ruxolitinib in children.
Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults. [2022]Ruxolitinib, a JAK1/2 inhibitor, is used to treat chronic graft versus host disease (cGVHD) in adult allogeneic hematopoietic stem cell transplant patients, but experience in children is limited, perhaps because of lack of pediatric dosing information. In this report, we describe our pediatric and young adult dosing strategy experience in cGVHD.
Co-Administration with Voriconazole Doubles the Exposure of Ruxolitinib in Patients with Hematological Malignancies. [2022]Ruxolitinib is newly approved for glucocorticoid-refractory acute graft-versus-host disease (GVHD) in patients undergoing allo-geneic hematopoietic stem-cell transplantation (allo-HSCT), and voriconazole is commonly used in allo-HSCT recipients for the prophylaxis or treatment of invasive fungal infections (IFIs). Drug-drug interaction (DDI) may occur between them because their metabolic pathways overlap and can be inhibited by voriconazole, including cytochrome P450 (CYP) isozymes 3A4 and 2C9.