Axatilimab + Ruxolitinib for Graft-versus-Host Disease

Recruiting at 82 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

Trial Summary

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.

What data supports the effectiveness of the drug Axatilimab + Ruxolitinib for Graft-versus-Host Disease?

Ruxolitinib, a component of the treatment, is approved for chronic graft-versus-host disease and has shown effectiveness in both acute and chronic forms of the condition, especially in patients who do not respond to steroids. ^{1 2 3 4 5}

Is the combination of Axatilimab and Ruxolitinib safe for treating graft-versus-host disease?

Ruxolitinib, used for treating graft-versus-host disease, has been generally well-tolerated in patients, though some have experienced serious side effects like infections and respiratory issues. Safety data from various studies suggest it is generally safe, but patients should be aware of potential risks. ^{1 2 6 7 8}

What makes the drug Axatilimab + Ruxolitinib unique for treating graft-versus-host disease?

This treatment combines Axatilimab, a novel drug, with Ruxolitinib, a JAK1/2 inhibitor that has shown effectiveness in treating graft-versus-host disease by targeting specific pathways involved in the immune response. This combination may offer a new approach for patients who do not respond to standard treatments like corticosteroids. ^{1 2 3 4 9}

What is the purpose of this trial?

This study will be conducted to determine the preliminary efficacy of axatilimab in combination with ruxolitinib and to assess the contribution of axatilimab to the combination treatment effect in participants with cGVHD.

Research Team

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Eligibility Criteria

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

My blood cancer has returned or I've been treated for a comeback after a stem cell transplant.

I have had more than one stem cell transplant from a donor.

Pregnant or breastfeeding

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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 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]

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]

References

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

New Indication for Ruxolitinib. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Ruxolitinib on acute graft-versus-host disease prophylaxis after modified donor lymphocyte infusion. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis. [2022]

4. 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]

5. United States 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. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Ruxolitinib early administration reduces acute GVHD after alternative donor hematopoietic stem cell transplantation in acute leukemia. [2021]

7. Germany 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. [2022]

8. England 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. [2022]

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

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