Ruxolitinib vs Prednisone for Graft-versus-Host Disease

Overseen By Jo Hill

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

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. ^{1 2 3 4 5}

Is 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. ^{1 3 5 6 7}

What 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. ^{4 6 8 9 10}

Research Team

Farhad Khimani, MD

Principal Investigator

Moffitt Cancer Center

Eligibility 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 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 (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 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, 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]

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 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]

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 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 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]

References

1. England 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

A Multicenter, Retrospective Study Evaluating Clinical Outcomes of Ruxolitinib Therapy In Heavily Pretreated Chronic GVHD Patients With Steroid Failure. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Ruxolitinib-induced reactivation of cytomegalovirus and Epstein-Barr virus in graft-versus-host disease. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Ruxolitinib in the Treatment of Steroid-Refractory Chronic Graft-versus-Host Disease. [2021]

6. Singapore pubmed.ncbi.nlm.nih.gov

Ruxolitinib add-on therapy in steroid-refractory graft-vs-host disease following hematopoietic cell transplantation: A single institutional experience. [2023]

7. Pakistan pubmed.ncbi.nlm.nih.gov

Role of Ruxolitinib in Steroid-Refractory Graft versus Host Disease in Patients Undergoing Allogeneic Stem Cell Transplant. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Ruxolitinib Treatment of Steroid-Refractory Graft-versus-Host Disease in Children: A Case Series and Review of the Literature. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Co-Administration with Voriconazole Doubles the Exposure of Ruxolitinib in Patients with Hematological Malignancies. [2022]