Ruxolitinib vs Prednisone for Graft-versus-Host Disease

Recruiting at 2 trial locations

Overseen By Sarah Starr

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Disqualifiers: Cardiovascular disease, Relapse malignancy, Hepatitis, HIV, 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: 6 months

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare two treatments, Ruxolitinib (a JAK inhibitor) and Prednisone (a corticosteroid), to determine which is more effective as a first-line treatment for chronic graft-versus-host disease (GVHD). GVHD occurs when donor cells attack the recipient's body after a bone marrow transplant. Participants must have chronic GVHD and require a first systemic treatment as determined by their doctor. The trial will assess whether Ruxolitinib serves as a suitable alternative to Prednisone in these cases. Candidates who have not previously received treatment for chronic GVHD and can take oral medications may qualify for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ruxolitinib, the treatment being tested, is generally well-tolerated. Earlier studies found that many patients with chronic graft-versus-host disease (GVHD) who took ruxolitinib experienced positive results. Although some serious side effects, such as low white blood cell counts and low platelet counts, have been reported, these were uncommon.

The FDA has already approved ruxolitinib for treating chronic GVHD when other treatments have failed, indicating it has passed safety checks for that use. Now, researchers are testing it as a first treatment option for GVHD, studying its safety for this new application. As this study is in the early stages, it is important to consult a healthcare provider if considering participation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GVHD?

Ruxolitinib is unique because it targets the JAK1 and JAK2 pathways, which play a key role in the inflammatory process involved in graft-versus-host disease (GVHD). Unlike the standard treatment of prednisone, which broadly suppresses the immune system, ruxolitinib offers a more precise approach by interrupting specific signaling pathways that drive inflammation. Researchers are excited about ruxolitinib because it has the potential to reduce symptoms more effectively while minimizing some of the side effects associated with traditional steroid treatments like prednisone.

What evidence suggests that this trial's treatments could be effective for chronic GVHD?

This trial will compare Ruxolitinib with Prednisone for treating graft-versus-host disease (GVHD). Research has shown that Ruxolitinib, which participants in this trial may receive, is effective for treating chronic GVHD. In one study, 78.3% of patients responded positively to Ruxolitinib. Patients taking Ruxolitinib also tend to experience fewer severe cases of chronic GVHD, and many can stop using corticosteroids while on Ruxolitinib. This evidence suggests that Ruxolitinib could be a promising treatment option for people with GVHD. ^{3 4 5 6 7}

Who Is on the Research Team?

Farhad Khimani, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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 agree to use birth control during the study.

I can take pills by mouth.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I do not have active hepatitis B, C, or HIV.

My cancer has returned after a transplant.

Participants with psychiatric illness/social situations that would limit compliance with study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Ruxolitinib or Prednisone as first-line therapy for chronic GVHD

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Prednisone
• Ruxolitinib

Trial Overview 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.

How Is the Trial Designed?

Group I: Ruxolitinib Treatment Arm Experimental Treatment 1 Intervention

Ruxolitinib is administered as 10 mg orally twice daily in 28-day cycles.

Group II: Prednisone Treatment Arm Active Control 1 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

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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

Published Research Related to This Trial

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]

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 14 pediatric patients with steroid-refractory graft-versus-host disease (SR-GVHD) treated with ruxolitinib, the overall response rate was 64.3%, indicating that ruxolitinib is an effective treatment option for children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

While ruxolitinib showed promising efficacy, 64.3% of patients experienced adverse effects, including cytopenia and infections, suggesting that while it is effective, monitoring for side effects is important in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib Treatment of Steroid-Refractory Graft-versus-Host Disease in Children: A Case Series and Review of the Literature. Yan, WL., Zhao, FY., Gu, ME., et al.[2023]

In a study involving 12 patients with hematological malignancies, the co-administration of voriconazole significantly increased the plasma levels of ruxolitinib, indicating a moderate drug-drug interaction that could enhance ruxolitinib's effects.

Due to this interaction, it is recommended to reduce the dose of ruxolitinib when given with voriconazole to avoid potential toxicity, highlighting the importance of drug monitoring for optimizing treatment in patients with acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-Administration with Voriconazole Doubles the Exposure of Ruxolitinib in Patients with Hematological Malignancies. Zhao, Y., Chen, P., Dou, L., et al.[2022]

In a study of 115 patients with steroid-refractory or -dependent chronic graft versus host disease (cGVHD), ruxolitinib demonstrated an overall response rate of approximately 48.6% at 3 months, indicating its efficacy in a heavily pretreated population.

After 12 months of treatment, 37.9% of patients were able to discontinue prednisone, and 63.8% could taper their dosage to less than 0.1 mg/kg, highlighting ruxolitinib's potential to reduce steroid dependency in cGVHD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Retrospective Study Evaluating Clinical Outcomes of Ruxolitinib Therapy In Heavily Pretreated Chronic GVHD Patients With Steroid Failure. White, J., Elemary, M., Linn, SM., et al.[2023]

Ruxolitinib (RUX) was well tolerated and led to significant improvements in chronic graft-versus-host disease (GVHD) symptoms in 19 allograft recipients, with high response rates in various affected areas, such as oral (92%) and cutaneous (82%) regions.

The treatment allowed for a reduction or discontinuation of steroid use in 68% of patients, demonstrating RUX's effectiveness as a steroid-sparing agent in managing chronic GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease. Khoury, HJ., Langston, AA., Kota, VK., et al.[2021]

In a study of 20 pediatric and young adult patients with chronic graft versus host disease (cGVHD), ruxolitinib showed a 70% overall response rate, with 2 patients achieving complete response and 12 achieving partial response after a median of 48 days.

The dosing strategy of ruxolitinib was effective in inhibiting JAK signaling, as indicated by decreased phosphorylation of STAT5 in lymphocytes, although some patients experienced side effects like neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults. Wang, YM., Teusink-Cross, A., Elborai, Y., 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]

Ruxolitinib, a selective JAK1/2 inhibitor, shows high overall response rates (over 70%) in treating steroid-refractory graft-versus-host disease (SR-GVHD), with response rates of 48% for acute and 58% for chronic cases among 57 patients studied.

However, initiating ruxolitinib treatment significantly increases the risk of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation, indicating the need for careful monitoring of viral loads in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib-induced reactivation of cytomegalovirus and Epstein-Barr virus in graft-versus-host disease. Lebon, D., Dujardin, A., Caulier, A., et al.[2023]

Citations

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

Ruxolitinib treatment outcomes in acute graft-versus-host ... Two-thirds of the patients were able to discontinue CSs, and two-thirds were estimated to be alive at three years from the initiation of ruxolitinib treatment.

2. hcp.jakafi.com hcp.jakafi.com/acute-graft-versus-host-disease/efficacy-early-intervention-results

Early Intervention Results Learn about the results of early intervention with Jakafi® (ruxolitinib) in patients with steroid-refractory acute graft-versus-host disease (aGVHD).

3. sciencedirect.com sciencedirect.com/science/article/pii/S2531137925001038

Long-term follow-up results of ruxolitinib as salvage ... Most patients presented with severe chronic graft-versus-host disease (15/23; 65.2%). The overall response rate was 78.3% (18/23) after a median treatment ...

4. 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 ... Prolonged ruxolitinib administration after allogeneic HCT is associated with low rates of clinically significant chronic GVHD.

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

Ruxolitinib plus steroids for acute graft versus host disease Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38916742/

Efficacy and safety of ruxolitinib in the treatment of chronic ... Overall, ruxolitinib was relatively well-tolerated and showed outcomes comparable to the REACH3 trial in a heavily pretreated patient population.

7. 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.