Ruxolitinib for Acute Graft-versus-Host Disease

(MAGIC V Trial)

Recruiting at 11 trial locations

Overseen By Janna Baez, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: John Levine

Must not be taking: JAK inhibitors

Disqualifiers: Uncontrolled infection, Severe organ dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called ruxolitinib, a JAK inhibitor, for individuals with acute graft-versus-host disease (GVHD). GVHD can occur after a stem cell transplant when donor cells attack the body. The standard treatment involves high-dose steroids, which do not always work well and can cause serious side effects. Researchers aim to determine if ruxolitinib alone is as effective as steroids for less severe GVHD and if it can improve outcomes when combined with steroids for more severe cases. Individuals who have developed GVHD after a stem cell transplant and have not yet tried systemic treatment may be eligible. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken systemic ruxolitinib or any JAK inhibitor within 7 days of starting the study. Topical or non-absorbed steroids are allowed.

Is there any evidence suggesting that ruxolitinib is likely to be safe for humans?

Research has shown that ruxolitinib is generally safe for treating acute graft-versus-host disease (GVHD). In previous studies, many patients tolerated the treatment well. However, some experienced side effects, such as blood-related issues like low platelet counts (thrombocytopenia) and low red blood cell counts (anemia). One study found that about 46% of patients had severe side effects, but these patients had undergone extensive previous treatments, which might have influenced the results.

Ruxolitinib is also approved for other conditions, indicating that its safety is well understood. In trials involving ruxolitinib, researchers will closely monitor participants for side effects to manage any potential problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for GVHD?

Most treatments for acute graft-versus-host disease (GVHD) involve corticosteroids, which suppress the immune system broadly. But ruxolitinib works differently, targeting specific pathways involved in the inflammation process. Researchers are excited about ruxolitinib because it can be administered in varying doses tailored to risk levels, potentially reducing side effects associated with higher doses. Additionally, in the high-risk group, ruxolitinib is paired with corticosteroids, offering a combined approach that might enhance efficacy while minimizing the need for prolonged steroid use.

What evidence suggests that ruxolitinib might be an effective treatment for acute GVHD?

Research has shown that ruxolitinib effectively treats acute graft-versus-host disease (GVHD). Studies have found that it helps 61% of patients with steroid-resistant acute GVHD, indicating improvement with this treatment. Another study found that 64.1% of patients were still alive after three years, suggesting potential long-term benefits. In this trial, participants will receive different dosages of ruxolitinib, with some also receiving systemic corticosteroids. Combining ruxolitinib with steroids has proven effective without causing serious side effects, such as a drop in blood cells. These findings suggest that ruxolitinib could be a promising option for those dealing with GVHD. ^{1 2 6 7 8}

Who Is on the Research Team?

John Levine, MD, MS

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for patients with acute graft-versus-host-disease (GVHD) after a bone marrow transplant. It's open to those who have symptoms like skin rash, jaundice, or digestive issues post-transplant. The study uses the Minnesota risk system to classify participants into different treatment groups based on their GVHD severity.

Inclusion Criteria

I am in the standard risk group for GVHD without severe skin involvement.

I have severe GVHD after donor lymphocyte infusion for mixed chimerism or poor graft function.

I haven't had systemic treatment for acute GVHD, but I may have used topical or non-absorbed steroids.

Exclusion Criteria

GVHD that developed after DLI for relapse is not allowed without study PI or medical monitor approval

Patients who are pregnant or nursing

I have symptoms similar to chronic GVHD or overlap syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ruxolitinib-based treatment for acute GVHD, with doses of 5 mg or 10 mg twice daily for 56 days, followed by a short taper

8 weeks

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for treatment response and safety, including assessment of GVHD flares and overall survival

1 year

Periodic visits for assessment

Extension

Participants may continue to be monitored for long-term outcomes such as non-relapse mortality and relapse

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The trial is testing ruxolitinib as a potential first-line treatment for GVHD, comparing it to standard high dose steroids like methylprednisolone. Patients are divided into two groups: one receives ruxolitinib alone and the other gets ruxolitinib with steroids, depending on their risk level determined by the Minnesota system.

How Is the Trial Designed?

Group I: Minnesota Standard Risk lower dose Experimental Treatment 1 Intervention

Patients receive lower dose ruxolitinib orally (PO) twice daily (BID) for 56 days then begin taper PO once daily (QD) for 1 week in the absence of disease progression or unacceptable toxicity

Group II: Minnesota Standard Risk higher dose Experimental Treatment 1 Intervention

Patients receive higher dose ruxolitinib PO BID for 56 days then begin taper PO BID for 1 week, followed by PO QD for 1 week in the absence of disease progression or unacceptable toxicity.

Group III: Minnesota High Risk Experimental Treatment 2 Interventions

Patients receive higher dose ruxolitinib PO BID for 56 days then begin taper PO BID for 1 week, followed by PO QD for 1 week in the absence of disease progression or unacceptable toxicity. Patients also receive systemic corticosteroid (methylprednisolone or similar) for a minimum of 3 days, then taper dose every 3-5 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

John Levine

Lead Sponsor

Trials

4

Recruited

230+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 29 children with steroid-refractory acute graft-versus-host disease (aGVHD), ruxolitinib demonstrated a high overall response rate of 72.4%, with 19 patients achieving complete response by a median of 41 days after treatment initiation.

Ruxolitinib was well-tolerated, with no severe hematological adverse events reported, suggesting it is a promising second-line treatment option for this condition, although further validation in larger trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib in children with steroid-refractory acute graft-versus-host disease: A retrospective multicenter study of the pediatric group of SFGM-TC. Laisne, L., Neven, B., Dalle, JH., et al.[2021]

In a study of 156 patients with steroid-refractory acute graft-versus-host disease (aGvHD), treatment with MSC-FFM showed an overall response rate of 46% in adults and 64% in children, indicating its potential effectiveness in this challenging condition.

The median overall survival for patients treated with MSC-FFM was 5.8 months, significantly better than the 28 days reported for patients not receiving MSC treatment, highlighting the potential benefit of MSC-FFM in improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease. Bonig, H., Verbeek, M., Herhaus, P., et al.[2023]

Ruxolitinib prophylaxis showed a 41.2% incidence of acute graft-versus-host disease (aGVHD) in patients after modified donor lymphocyte infusion, indicating it can help reduce the severity of aGVHD in high-risk leukemia patients post-transplant.

Among the 17 patients studied, 58.8% achieved a complete response, suggesting that ruxolitinib may effectively maintain the graft-versus-leukemia (GVL) effect while managing aGVHD, despite a median follow-up of only 8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib on acute graft-versus-host disease prophylaxis after modified donor lymphocyte infusion. Tang, Y., Yang, D., Xie, R., et al.[2023]

In a study of 57 patients undergoing alternative donor transplantation for acute leukemia, early application of ruxolitinib significantly reduced the incidence of acute graft-versus-host disease (aGVHD) compared to the control group (22% vs. 50%).

Ruxolitinib was well tolerated, with no significant differences in overall survival or disease-free survival between the ruxolitinib and control groups, indicating its safety and efficacy in preventing aGVHD without compromising other health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib early administration reduces acute GVHD after alternative donor hematopoietic stem cell transplantation in acute leukemia. Zhang, B., Chen, L., Zhou, J., et al.[2021]

In an expanded access program involving 609 patients (60 with acute GVHD and 549 with chronic GVHD), ruxolitinib demonstrated a tolerable safety profile, with serious adverse events (SAEs) reported in 68.3% of acute and 33.9% of chronic GVHD patients.

The most common SAEs included infections, with sepsis and respiratory failure being prevalent in acute GVHD, indicating that while ruxolitinib is generally well-tolerated, careful monitoring for infections is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety analysis of patients who received ruxolitinib for steroid-refractory acute or chronic graft-versus-host disease in an expanded access program. Schroeder, MA., Hari, PN., Blithe, A., et al.[2022]

In a study of 35 patients with steroid-refractory chronic graft-versus-host disease (cGVHD), ruxolitinib demonstrated a high overall response rate of 89%, with 26% achieving complete response after a median of 4 weeks of treatment.

The long-term follow-up showed that 67% of surviving patients were free of immunosuppression, indicating ruxolitinib's potential as a safe and effective second-line therapy for cGVHD, with manageable hematologic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Ruxolitinib in the Treatment of Steroid-Refractory Chronic Graft-versus-Host Disease. Ferreira, AM., Szor, RS., Molla, VC., et al.[2021]

In a study of 53 pediatric patients with graft-versus-host disease (GVHD), ruxolitinib demonstrated a high overall response rate of 75.5%, with 80.6% efficacy in chronic GVHD (cGVHD) cases compared to 64.7% in acute GVHD (aGVHD).

Ruxolitinib treatment allowed 39% of patients to discontinue steroids and 22.2% to reduce their steroid dosage, although it was associated with a high incidence of adverse events (94.1%) in the aGVHD group, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Ruxolitinib for Acute/Chronic Graft-versus-Host Disease in Children: A Retrospective Study. Yang, W., Zhu, G., Qin, M., et al.[2022]

In a study of 20 patients with steroid-refractory graft versus host disease (GVHD) treated with Ruxolitinib, the overall response rate was high, with 85.7% for acute GVHD and 84.6% for chronic GVHD, indicating its efficacy as a second-line therapy.

Ruxolitinib demonstrated a favorable safety profile, with 80% of patients experiencing adverse events, but only 20% having severe (grade III/IV) events, suggesting it is a safe option for patients who do not respond to steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Ruxolitinib in Steroid-Refractory Graft versus Host Disease in Patients Undergoing Allogeneic Stem Cell Transplant. Javed, H., Chaudhry, Q., Shahbaz, N., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12283849/

Ruxolitinib treatment outcomes in acute graft-versus-host ... The three-year OS was 64.1% (95% CI: 48.2–76.3). Ruxolitinib appears effective and safe in real-world practice. The presented data is in line with the results ...

2. nature.com nature.com/articles/s41392-024-01987-x

Ruxolitinib plus steroids for acute graft versus host disease In a study involving aGVHD patients with fibrosis, ruxolitinib at 5 mg/day was found to be effective without causing severe cytopenia, whereas ...

3. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04731-1

Real-world data suggest effectiveness of the allogeneic ... A recent real-world analysis of outcomes for 64 adult RR-aGvHD patients not treated with MSCs reports survival of 20%, 16% and 10% beyond 6, 12 and 24 months, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473050224002362

The role of ruxolitinib in the management of acute GVHD Conclusion. Ruxolitinib has an ORR of 61 % for SR-aGVHD, making it a safe and effective therapy choice in real-world settings.

5. ashpublications.org ashpublications.org/blood/article/145/20/2312/536227/Low-rates-of-chronic-graft-versus-host-disease

Low rates of chronic graft-versus-host disease with ruxolitinib ... Overall survival and progression-free survival at 2 years were 76% and 68%, respectively. Prolonged administration of ruxolitinib following HCT ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00809

Final Analysis From the Randomized Phase III REACH2 Trial Numerically higher chronic GVHD rates were noted with ruxolitinib than with BAT from 12 months; however, 95% confidence intervals overlapped.

7. astctjournal.org astctjournal.org/article/S1083-8791(18)31084-X/fulltext

Safety Analysis of Patients Who Received Ruxolitinib for ... Patients in the RUX EAPs were heavily pretreated, and more than half of the patients reported GI GVHD. SAEs were reported in almost half of the patients (46.4%) ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1917635

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus ... Adverse events up to day 28 were mainly cytopenias, particularly thrombocytopenia and anemia.