Axatilimab + Ruxolitinib for Graft-versus-Host Disease

Recruiting at 92 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Incyte Corporation

Must not be taking: Corticosteroids, JAK inhibitors

Disqualifiers: Pancreatitis, Thromboembolic events, 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 evaluate the effectiveness of a new drug combination, axatilimab (an experimental treatment) and ruxolitinib, for treating individuals with moderate to severe chronic graft-versus-host disease (cGVHD), a condition where donor cells attack the recipient's body after a stem cell transplant. The trial will compare three groups: one group will receive both axatilimab and ruxolitinib, another will receive only ruxolitinib, and the third will be treated with corticosteroids alone. Suitable candidates for this trial are those who have required systemic therapy for new and moderate to severe cGVHD following one stem cell transplant. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received systemic corticosteroids or started certain treatments like CNIs or mTOR inhibitors within 2 weeks before the trial begins, and you must not have used a JAK inhibitor within 8 weeks before joining.

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

Previous studies have shown that ruxolitinib is generally well-tolerated by patients, with no unexpected side effects. Its safety profile aligns with earlier research findings. Most patients experienced either complete or partial improvements, indicating the treatment's effectiveness with minimal issues.

Research has shown that the FDA has already approved axatilimab for treating chronic graft-versus-host disease (GVHD), confirming its well-known safety. When combined with other treatments, axatilimab has benefited patients with severe GVHD, further supporting its safe use.

Overall, both treatments have been generally safe for people with chronic GVHD. While combining treatments can sometimes be risky, current evidence indicates that each drug can be used safely. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of axatilimab and ruxolitinib for treating graft-versus-host disease (GVHD) because it offers a novel approach to managing this challenging condition. Unlike the standard of care, which typically involves corticosteroids, axatilimab targets the CSF-1 receptor, which plays a key role in inflammation and immune response. This mechanism is different from ruxolitinib, which inhibits JAK1 and JAK2 pathways to reduce immune activity. By combining these two drugs, there's potential for a more effective treatment that addresses both inflammation and immune system overactivity, offering hope for better outcomes in GVHD patients.

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

Research has shown that combining axatilimab and ruxolitinib can help treat chronic graft-versus-host disease (cGVHD). In this trial, participants in Treatment Group A will receive this combination, which demonstrated a 69% improvement rate in previous studies. Axatilimab blocks a protein that causes inflammation, while ruxolitinib reduces swelling and immune reactions. Participants in Treatment Group B will receive ruxolitinib alone, which has also proven effective for cGVHD, with a 70% improvement rate in some studies. Overall, these treatments have shown promising results for people with cGVHD. ^{1 2 3 4 6}

Who Is on the Research Team?

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older who have been newly diagnosed with moderate to severe chronic Graft-Versus-Host Disease (cGVHD) and need systemic therapy. They should not be dependent on platelet transfusions, have a certain level of white blood cells and platelets, and must commit to preventing pregnancy or fathering children.

Inclusion Criteria

Willingness to avoid pregnancy or fathering children

I have had one stem cell transplant from any donor.

I have a new severe reaction from a transplant that needs treatment.

Exclusion Criteria

I have a history of pancreatitis.

Pregnant or breastfeeding

I do not have serious heart problems like uncontrolled high blood pressure or recent heart attacks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive axatilimab in combination with ruxolitinib or corticosteroids alone

6 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years and 30 days

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Axatilimab
• Corticosteroids
• Ruxolitinib

Trial Overview The study tests the safety and effectiveness of Axatilimab in combination with Ruxolitinib compared to standard treatments like corticosteroids for cGVHD. It aims to see if adding Axatilimab improves treatment outcomes.

How Is the Trial Designed?

Group I: Treatment Group C Experimental Treatment 1 Intervention

Corticosteroids alone will be administered at a protocol defined starting dose.

Group II: Treatment Group B Experimental Treatment 1 Intervention

Ruxolitinib will be administered at a protocol defined starting dose.

Group III: Treatment Group A Experimental Treatment 2 Interventions

Axatilimab will be administered at a protocol defined starting dose plus ruxolitinib at a protocol defined starting dose.

Axatilimab is already approved in United States for the following indications:

Approved in United States as Axatilimab for:

• Chronic Graft-Versus-Host Disease

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 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 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 29 patients with graft versus host disease (GvHD), Ruxolitinib exposure was found to be significantly higher than in myelofibrosis patients, indicating altered drug metabolism in GvHD.

Increased Ruxolitinib levels were linked to reduced drug clearance and the use of CYP3A4 or CYP2C9 inhibitors, suggesting that higher trough concentrations may indicate a risk of toxicity and necessitate careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice-a prospective single-center trial. Isberner, N., Kraus, S., Grigoleit, GU., et al.[2022]

Ruxolitinib (Jakafi) has received approval for the treatment of chronic graft-vs-host disease, indicating its efficacy in managing this condition.

The approval of ruxolitinib highlights its role as a kinase inhibitor, which works by targeting specific pathways involved in the immune response, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indication for Ruxolitinib. Aschenbrenner, DS.[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 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 8 patients with acute or chronic graft versus host disease (GVHD) who were unresponsive to standard treatments, ruxolitinib demonstrated a high overall response rate of 85%, with 50% achieving complete response.

Ruxolitinib was well-tolerated, indicating it could be a promising rescue therapy for patients suffering from refractory GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis. Sarmiento Maldonado, M., Ramírez Villanueva, P., Bertín Cortes-Monroy, P., et al.[2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06388564

NCT06388564 | A Study to Evaluate the Safety and ... A Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease.

2. targetedonc.com targetedonc.com/view/axatilimab-plus-ruxolitinib-belumosudil-may-yield-benefit-in-cgvhd

Axatilimab Plus Ruxolitinib/Belumosudil May Yield Benefit ... In a retrospective cohort of patients with severe chronic GVHD, combination axatilimab with other GVHD therapies led to clinical benefit.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11713947/

Axatilimab - PMC The best overall response rate at any point during the study was 69% (27 of 39 patients; 95% CI: 52%-83%). This response rate was similar among ...

4. mskcc.org mskcc.org/cancer-care/clinical-trials/24-318

A Phase 2 Study of Axatilimab Plus Ruxolitinib in Adults ... Ruxolitinib blocks JAK proteins, which may reduce inflammation (swelling) and immune system reactions related to GVHD. Axatilimab blocks a protein called CSF-1R ...

5. onclive.com onclive.com/view/axatilimab-shakes-up-cgvhd-treatment-and-looks-to-move-to-earlier-line-in-paradigm

Axatilimab Shakes Up cGVHD Treatment and Looks to ... In REACH3, the overall response rate (ORR) through week 24 was 70% in the ruxolitinib arm (n = 165) compared with 57% in the best available ...

6. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-more-50-abstracts-accepted-presentation-2025

Press Release Additionally, we look forward to sharing the results from axatilimab in graft-versus-host disease (GVHD) and tafasitamab in follicular lymphoma ...