Ruxolitinib for Chronic Graft-versus-Host Disease
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Children's Hospital Medical Center, Cincinnati
Must be taking: Ruxolitinib
Must not be taking: Corticosteroids
Disqualifiers: Active infection, Malignancy, Thrombosis, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?While hematopoietic stem cell transplant (HSCT) is an effective therapy, graft versus host disease (GVHD) is the most significant complication after HSCT. Corticosteroids (or steroids) have been the mainstay of treatment for chronic GVHD for many decades now. Increasingly, newer immunosuppressive and immunomodulating agents are being studied in adults and children affected by cGVHD. Ruxolitinib is one of these promising newer agents, which has been shown to be effective in the treatment of cGVHD in both children and adults. Currently, ruxolitinib is generally added to a patient's treatment regimen after (or with) a course of high dose steroids.
The purpose of this study is to examine the effectiveness of upfront single agent ruxolitinib for cGVHD.
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 require that you are on a low dose of steroids or can reduce your steroid dose to a low level within a month. If you are on high-dose steroids, you may not be eligible.
What data supports the effectiveness of the drug Ruxolitinib for chronic graft-versus-host disease?
Research shows that Ruxolitinib is effective for patients with chronic graft-versus-host disease who do not respond to steroids, with a significant number of patients experiencing improvement in their condition. In one study, 89% of patients showed a positive response, and many were able to reduce or stop other medications.
12345Is Ruxolitinib safe for humans?
Ruxolitinib has been used in patients with graft-versus-host disease, and while it is generally tolerated, some serious side effects like infections, sepsis (a severe infection), and respiratory issues have been reported. These findings suggest that while it can be safe, there are risks of serious side effects that need to be monitored.
12678How is the drug Ruxolitinib unique in treating chronic graft-versus-host disease?
Ruxolitinib is unique because it is an oral drug that specifically targets the JAK1/JAK2 pathways, which are involved in the development of graft-versus-host disease. Unlike other treatments, it has shown promising results in patients who do not respond to standard steroid treatments.
89101112Eligibility Criteria
This trial is for individuals who have received a stem cell transplant and are now dealing with chronic graft versus host disease (cGVHD), which can affect various organs. Participants should not have previously used high-dose steroids or other immunosuppressants for cGVHD.Inclusion Criteria
I have not had systemic treatment for chronic GVHD but may have been treated for acute GVHD.
I have a new diagnosis of severe chronic graft versus host disease needing treatment.
I am between 12 and 30 years old.
+6 more
Exclusion Criteria
I currently have a serious infection.
I have not had a clot-related event like a heart attack or stroke in the last 6 months.
My blood counts are low and not improving with standard care.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive upfront single agent ruxolitinib for chronic graft-versus-host disease
12 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study is testing the effectiveness of Ruxolitinib as an initial, standalone treatment for cGVHD. The goal is to see if using this drug early on, without combining it with steroids, can help manage symptoms better.
1Treatment groups
Experimental Treatment
Group I: Ruxolitinib TreatmentExperimental Treatment1 Intervention
Ruxolitinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Jakafi for:
- Intermediate or high-risk myelofibrosis
- Polycythemia vera
- Steroid-refractory acute graft-versus-host disease
- Chronic graft-versus-host disease
- Vitiligo
🇪🇺 Approved in European Union as Jakavi for:
- Intermediate or high-risk myelofibrosis
- Polycythemia vera
- Steroid-refractory acute graft-versus-host disease
- Chronic graft-versus-host disease
- Non-segmental vitiligo
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cincinnati Children's Hospital Medical CenterCincinnati, OH
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Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
References
New Indication for Ruxolitinib. [2023]The kinase inhibitor ruxolitinib (Jakafi) is now approved to treat chronic graft-vs-host disease.
Ruxolitinib on acute graft-versus-host disease prophylaxis after modified donor lymphocyte infusion. [2023]To evaluate the effectiveness of ruxolitinib on acute graft-versus-host disease (aGVHD) prophylaxis and its impact on graft-versus-leukemia (GVL) effect in patients after modified donor lymphocyte infusion (mDLI).
Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease. [2021]Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval, .388 to .673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost.
Ruxolitinib in children with steroid-refractory acute graft-versus-host disease: A retrospective multicenter study of the pediatric group of SFGM-TC. [2021]We conducted a national multicenter retrospective study in France to evaluate the efficacy and tolerance of ruxolitinib in children with steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplant.
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.
Safety analysis of patients who received ruxolitinib for steroid-refractory acute or chronic graft-versus-host disease in an expanded access program. [2022]Outside of clinical trials and before commercial availability for acute and chronic graft-versus-host disease (GVHD), the Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was available to US patients with steroid-refractory GVHD through an open-label, multicenter expanded access program (EAP) sponsored by Incyte Corporation. To assess the safety of ruxolitinib, data on serious adverse events (SAEs) reported among patients in the EAP were collected. Patients ≥12 years old who received allogeneic hematopoietic cell transplantation for a hematologic malignancy and developed any-grade acute or chronic steroid-refractory GVHD received ruxolitinib at a starting dose of 5 mg twice daily (BID; acute GVHD) or 10 mg BID (chronic GVHD). At data extraction (May 8, 2020), 60 patients with acute GVHD and 549 with chronic GVHD were enrolled. In the acute and chronic GVHD cohorts, 41 (68.3%) and 186 (33.9%) patients, respectively, had ≥1 SAE. Sepsis (8.3%) and respiratory failure (6.7%) were the most common SAEs in the acute GVHD cohort, and pneumonia (4.9%), sepsis (3.8%), and lung infection (3.5%) in chronic GVHD. Infection SAEs were reported in 23.3% and 20.0% of patients with acute and chronic GVHD, respectively. Overall, these safety findings demonstrate the tolerability of ruxolitinib in steroid-refractory GVHD.
Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice-a prospective single-center trial. [2022]Knowledge on Ruxolitinib exposure in patients with graft versus host disease (GvHD) is scarce. The purpose of this prospective study was to analyze Ruxolitinib concentrations of GvHD patients and to investigate effects of CYP3A4 and CYP2C9 inhibitors and other covariates as well as concentration-dependent effects.
Ruxolitinib for the treatment of graft-versus-host disease. [2021]Introduction: Ruxolitinib is an oral selective JAK1/JAK2 inhibitor, initially approved by the FDA for the treatment of intermediate-2 or high-risk myelofibrosis and patients with polycythemia vera who have had an inadequate response or are intolerant to hydroxyurea.Areas covered: Accumulating evidence supports the role of JAK1/JAK2 pathways in the pathogenesis of graft-versus-host disease (GVHD), and preclinical studies have demonstrated promising efficacy of ruxolitinib in treatment/prevention of GVHD. Early clinical observations that ruxolitinib was effective in treatment of steroid-refractory (SR) acute and chronic GVHD led to the development of prospective clinical trials; Phase II REACH1 (NCT02953678), Phase III REACH2 (NCT02913261), and REACH3 (NCT03112603). Based on the data from the REACH1 trial, ruxolitinib was approved by the FDA in May 2019 for SR acute GVHD in adult and pediatric patients 12 years and older.Expert opinion: Ruxolitinib and other JAK1/JAK2 inhibitors hold promise in other treatment settings such as GVHD prevention and/or first-line therapy.
Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis. [2022]Ruxolitinib is a potent inhibitor of JAK1/2 with proven efficacy in myelofibrosis. In recent years, research in graft versus host disease (GVHD) has revealed the role of activation of JAK pathways in alloreactive lymphocytes. Some reports have shown significant responses in refractory GVHD patients.
Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. [2023]Ruxolitinib is a tyrosine kinase inhibitor targeting the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways. Ruxolitinib is used to treat myelofibrosis, polycythemia vera and steroid-refractory graft-versus-host disease in the setting of allogeneic stem-cell transplantation. This review describes the pharmacokinetics and pharmacodynamics of ruxolitinib.
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.
Efficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation. [2022]Corticosteroid-refractory graft-versus-host disease (SR-GVHD) remains a significant source of morbidity after allogeneic hematopoietic cell transplantation. No standard therapy exists in this setting; however, recent studies have demonstrated a very promising role for ruxolitinib, an oral Janus kinase 1/2 inhibitor. With increasing evidence of efficacy for SR-GVHD, limited data exist describing complications of ruxolitinib use, specifically infectious complications during use in SR-GVHD. In this study we report outcomes and infectious complications at our institution with ruxolitinib use. Overall, 43 patients were treated with ruxolitinib for SR-GVHD, 19 for acute SR-GVHD and 24 for chronic SR-GVHD. With respect to acute SR-GVHD, 15 patients had grade III acute GVHD and 4 patients had grade IV acute GVHD. At 28 days, a response rate of 84% was detected. With respect to chronic SR-GVHD, 16 patients had moderate refractory disease and 8 had severe refractory disease. At around 28 days, a 63% response rate was detected. Overall, 42% of patients (n = 18) treated with ruxolitinib had a documented infectious event. Infectious events were significantly more common among patients treated for acute SR-GVHD (P