Ruxolitinib for Graft-versus-Host Disease

No longer recruiting at 219 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must be taking: Corticosteroids

Must not be taking: JAK inhibitors

Disqualifiers: Relapsed malignancy, Failed alloSCT, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of ruxolitinib, a JAK inhibitor, compared to the best available treatments for individuals with steroid-refractory chronic graft-versus-host disease (cGvHD) following a bone marrow transplant. Researchers are testing ruxolitinib because standard steroid treatments have not been effective for these participants. Suitable candidates have undergone a bone marrow transplant, are experiencing moderate to severe cGvHD, and have not responded to steroids. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must be willing to be treated with one of the specified best available therapy options. You can continue using corticosteroids if they are for cGvHD and meet certain conditions.

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

A previous study found ruxolitinib to be safe. Over two years, researchers discovered no new safety issues, indicating that people generally tolerate the treatment well. Another study found that some patients experienced mild side effects, such as fever or low blood cell counts. However, no serious health problems were linked to ruxolitinib. These findings suggest that ruxolitinib is generally safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ruxolitinib is unique because it offers a new approach for patients with steroid-refractory chronic Graft vs. Host Disease (GvHD), a condition often treated with immunosuppressants like corticosteroids. Unlike standard treatments that broadly suppress the immune system, Ruxolitinib specifically targets and inhibits the JAK1 and JAK2 enzymes, which play a crucial role in the inflammatory process. This targeted action could potentially reduce inflammation more effectively while minimizing some side effects associated with broader immunosuppression. Researchers are excited about Ruxolitinib because it may offer improved outcomes for patients who have not responded well to existing therapies.

What evidence suggests that ruxolitinib might be an effective treatment for steroid-refractory chronic graft-versus-host disease?

Research has shown that ruxolitinib, a type of medication, holds potential for treating various health conditions. In this trial, participants will receive either ruxolitinib or the best available therapy. Earlier studies demonstrated that patients using ruxolitinib experienced noticeable symptom improvements compared to those on other treatments. For instance, a cream version of ruxolitinib significantly reduced skin symptoms within 12 hours of application. Additionally, long-term use of ruxolitinib has been associated with fewer blood clot issues than other treatments. These findings suggest that ruxolitinib could effectively manage symptoms in conditions like chronic graft-versus-host disease that do not respond to steroids. ^{6 7 8 9 10}

Who Is on the Research Team?

Rodica Morariu-Zamfir

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

Inclusion Criteria

A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, OR Disease persistence without improvement despite continued treatment with prednisone at > 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, OR Increase to prednisolone dose to > 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose

Participant must accept to be treated with only one of the following BAT options on Cycle 1 Day 1 (additions and changes are allowed during the course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib

Have undergone allogeneic stem cell transplantation (alloSCT) from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible

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 Best Available Therapy for chronic graft-versus-host disease

28 weeks

7 cycles of 4 weeks each

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

How Is the Trial Designed?

Group I: Ruxolitinib Experimental Treatment 1 Intervention

Ruxolitinib for the treatment period and extension period.

Group II: Best Available Therapy Active Control 9 Interventions

Best available therapy for the treatment period and extension period, with optional crossover to ruxolitinib after Cycle 6.

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

Who Is Running the Clinical Trial?

Incyte Corporation

Lead 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

Ruxolitinib, a JAK1/2 inhibitor, was evaluated in a Phase Ib study with 42 patients, primarily with pancreatic cancer, showing it was generally safe and well tolerated when combined with gemcitabine, although the study was terminated early due to interim results from another study.

The overall response rate for the combination therapy was 38.5% in the pooled cohorts, but the study was halted before determining maximum tolerated doses, indicating that while there was some efficacy, the combination will not be pursued further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors. Bauer, TM., Patel, MR., Forero-Torres, A., et al.[2022]

Ruxolitinib, a JAK1/2 inhibitor recently approved for Myelofibrosis, significantly reduces nitric oxide production and pro-inflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in RAW 264.7 cells, indicating its potential anti-inflammatory effects.

In an endotoxemia model with C57 mice, ruxolitinib improved survival rates by 70% and decreased serum levels of pro-inflammatory cytokines, suggesting it may be a promising therapeutic candidate for sepsis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib protects lipopolysaccharide (LPS)-induced sepsis through inhibition of nitric oxide production in mice. Li, L., He, X., Wang, X., et al.[2022]

Ruxolitinib, a Janus kinase inhibitor, showed promising efficacy in treating Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), with 7 out of 12 patients achieving complete remission and 2 achieving partial remission after treatment.

The study highlights the potential of targeting the JAK-STAT signaling pathway in Ph-like ALL patients, particularly those with specific gene fusions affecting JAK2 and EPOR, suggesting that ruxolitinib could be a valuable addition to standard therapy for this high-risk leukemia subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ruxolitinib in acute lymphoblastic leukemia: A systematic review. Kołodrubiec, J., Kozłowska, M., Irga-Jaworska, N., et al.[2022]

Ruxolitinib, a Janus kinase inhibitor approved for myelofibrosis and polycythemia vera, shows promising efficacy in treating dermatologic conditions like atopic dermatitis, psoriasis, and vitiligo, based on data from clinical trials.

The evidence for ruxolitinib's effectiveness in alopecia areata is mixed, varying between topical and oral formulations, indicating the need for further research to clarify its role in treating various skin disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label Studies on the Use of Ruxolitinib in Dermatology. Tegtmeyer, K., Ravi, M., Zhao, J., et al.[2021]

Ruxolitinib is an effective treatment for patients with polycythaemia vera (PV) who do not respond well to hydroxyurea, showing superior results in reducing hematocrit and spleen size after 32 weeks in the phase III RESPONSE trial.

The drug is generally well tolerated, with manageable side effects like mild to moderate anemia and thrombocytopenia, making it a valuable option for PV patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib: A Review in Polycythaemia Vera. McKeage, K.[2021]

Ruxolitinib, a JAK-2 inhibitor used for treating myeloproliferative neoplasms, is generally associated with very rare skin toxicity, but an unusual case of erythematous skin eruption with necrotic centers was observed in a patient with primary myelofibrosis.

This case highlights the need for increased awareness of potential skin side effects from ruxolitinib, especially as JAK-2 inhibitors may be used more widely in dermatological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. Dasanu, CA.[2021]

Janus kinase inhibitors (JAKi) are commonly used for treating immune-mediated inflammatory diseases like psoriatic arthritis, but recent studies have raised safety concerns, particularly in patients over 50 with cardiac risk factors.

This review summarizes the latest safety data for various JAKi, including tofacitinib and upadacitinib, and discusses findings from an oral surveillance study to provide context for these safety issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. Nash, P.[2022]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

A study analyzing 126,815 safety reports found that the JAK inhibitors ruxolitinib, tofacitinib, and baricitinib are associated with increased risks of infectious adverse events, particularly viral, fungal, and mycobacterial infections.

Tofacitinib specifically showed a significant association with gastrointestinal perforation events, while no significant increase in major cardiovascular events was observed, indicating a need for careful monitoring of these risks in patients using JAK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Hoisnard, L., Lebrun-Vignes, B., Maury, S., et al.[2023]

In a phase 3 study involving 222 patients with polycythemia vera, ruxolitinib significantly outperformed standard therapy, achieving hematocrit control in 60% of patients and a 35% reduction in spleen volume in 38% of patients, compared to only 20% and 1% respectively in the standard therapy group.

Ruxolitinib also led to a higher rate of complete hematologic remission (24% vs. 9%) and a greater reduction in total symptom scores (49% vs. 5%), while maintaining a manageable safety profile with low rates of severe anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib versus standard therapy for the treatment of polycythemia vera. Vannucchi, AM., Kiladjian, JJ., Griesshammer, M., et al.[2022]

In a 3-year follow-up of the COMFORT-II Trial involving 219 patients with myelofibrosis, ruxolitinib demonstrated sustained reductions in spleen size and improved quality of life, with 45% of patients remaining on treatment after 3 years.

Ruxolitinib was well tolerated, with manageable side effects like anemia and thrombocytopenia, and it was associated with longer overall survival compared to the best available therapy, indicating its efficacy and safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Cervantes, F., Vannucchi, AM., Kiladjian, JJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11193693/

Efficacy, Safety, and Long-Term Disease Control of ... A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies.

2. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35661

Ten years of experience with ruxolitinib since approval for ... Thrombotic events occurred in 2.7% versus 4.2% of patients in the ruxolitinib group (median follow-up, 26 months) versus patients continuing on ...

3. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-results-phase-3-clinical-trials-evaluating

Incyte Announces Results of Phase 3 Clinical Trials ... As a result, significantly more patients who applied ruxolitinib cream 1.5% versus vehicle control achieved overall treatment success (11.9% vs ...

4. opzelura.com opzelura.com/vitiligo/clinical-trial-results

Repigmentation Results 75% improvement to vitiligo areas on the face was achieved at 6 months in 29.9% of patients using OPZELURA in 2 separate studies compared with 7.5% and 12.9% of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950312425000028

Therapeutic efficacy and safety of topical ruxolitinib in mild- ... The main results were a significant reduction in pruritus observed approximately 12 h after the first application of ruxolitinib cream (0.75 % and 1.5 %), ...

6. opzelurahcp.com opzelurahcp.com/vitiligo/adverse-event-profile

safety data through 2 years 1 - Opzelura HCP Safety data at Week 104 is consistent with the phase III studies and no additional safety signals were observed1,2. In the long-term extension through 104 ...

7. hcp.jakafi.com hcp.jakafi.com/acute-graft-versus-host-disease/safety-adverse-events

Safety Profile of Jakafi in aGVHD Safety results for Jakafi ® (ruxolitinib) in REACH1 · Nonhematologic Adverse Reactions Occurring in ≥15% of Patients · Selected Laboratory Abnormalities Worsening ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10866801/

Real-World Use of Ruxolitinib Cream: Safety Analysis at 1 ... Postmarketing safety data from the year following approval suggest ruxolitinib cream is generally well tolerated, without significant systemic ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/215309s007lbl.pdf

OPZELURA® (ruxolitinib) cream, for topical use Application site reactions, pyrexia, and decreased white blood cell were reported more frequently in pediatric subjects ages 2 to ll years compared to adults ...

10. eocco.com eocco.com/-/media/EOCCO/PDFs/Formulary/Ruxolitinib-_Jakafi_EOCCO.pdf

ruxolitinib (Jakafi®, Opzelura™) Safety data out to 52 weeks did not reveal additional safety warnings. No serious AE occurred as a result of ruxolitinib (Opzelura) treatment; however,.