Ruxolitinib for Graft-Versus-Host Disease Prevention

Recruiting at 1 trial location

Overseen By Ramzi Abboud, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must be taking: Tacrolimus, Mycophenolate mofetil, Cyclophosphamide

Must not be taking: Investigational drugs, Antithymocyte globulin

Disqualifiers: Prior allogeneic transplant, HIV, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Ruxolitinib (also known as Jakafi, Jakavi, or Opzelura), with or without Abatacept, to help prevent graft-versus-host disease (GVHD) in individuals undergoing bone marrow transplants from partially matched donors. GVHD can occur after a transplant when new immune cells attack the body. The trial aims to determine if these drugs can reduce GVHD without affecting the transplant's positive effects on cancer. Individuals with certain blood cancers, such as leukemia or lymphoma, planning a transplant from a family member donor, might find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on investigational drugs or immunosuppressive doses of steroids, you may need to stop them before joining the trial.

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

Research has shown that ruxolitinib is generally safe for treating graft-versus-host disease (GVHD). In past studies, patients taking ruxolitinib had safety outcomes similar to those in another large study called REACH3, even if they had tried other treatments before. Two years after treatment, 76% of patients were still alive, and 68% did not experience worsening of their disease. This suggests that long-term use of ruxolitinib after a transplant can be safe.

For the combination of ruxolitinib and abatacept, research is ongoing. Early results indicate that using abatacept to prevent GVHD looks promising, but more safety information about this combination is still being collected.

Overall, both ruxolitinib alone and with abatacept seem well-tolerated, but more research is needed for the combination therapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for graft-versus-host disease (GVHD) because they offer innovative approaches to prevention. Ruxolitinib is unique because it targets the JAK1 and JAK2 pathways, potentially reducing the immune response that leads to GVHD. The addition of abatacept, which blocks a specific protein involved in T-cell activation, offers a dual approach by further dampening the immune response. Unlike standard treatments, which often rely on broad immunosuppressants, these treatments aim to precisely modulate immune activity, potentially leading to more effective prevention with fewer side effects.

What evidence suggests that this trial's treatments could be effective for preventing graft-versus-host disease?

Research has shown that ruxolitinib effectively treats graft-versus-host disease (GVHD). One study found that patients with acute GVHD who took ruxolitinib had about three times better response rates by day 28 compared to those on standard treatment. Additionally, 64.1% of patients treated with ruxolitinib were still alive after three years. In this trial, some participants will receive ruxolitinib alone, while others will receive a combination of ruxolitinib and abatacept, which blocks a specific immune signal. Although detailed results for this combination are still being gathered, early data suggest extra benefits when used with abatacept. Overall, ruxolitinib has shown strong results in managing GVHD. ^{2 3 4 5 6}

Who Is on the Research Team?

Ramzi Abboud, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with certain blood cancers who are in remission and have a closely related family member as a donor. They must be healthy enough for stem cell harvesting, not HIV or HTLV positive, and agree to use birth control. People can't join if they've had previous allogeneic transplants, active hepatitis or HIV, severe allergies to study drugs, or are pregnant.

Inclusion Criteria

I am scheduled for a specific type of stem cell transplant from a half-matched donor.

I can take care of myself and am up and about more than 50% of my waking hours.

My blood cancer is in a specific stage of remission.

Exclusion Criteria

Known hypersensitivity to study agents

I have or had active tuberculosis.

I am not taking high doses of steroids that weaken my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ruxolitinib starting on Day -3 and continuing until Day 180, with dose adjustments based on recovery criteria

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Expansion Phase

Continuation of Ruxolitinib treatment with dose adjustments based on patient recovery

Duration not specified

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The trial tests Ruxolitinib's ability to prevent graft-versus-host disease (GVHD) and cytokine release syndrome after receiving stem cells from half-matched donors. It aims to see if the drug can protect patients without harming the anti-cancer effects of the transplant.

How Is the Trial Designed?

Group I: Regimen 2: Ruxolitinib + Abatacept Experimental Treatment 2 Interventions

* Ruxolitinib at 5 mg twice per day (BID) beginning on Day -3 and continuing until Day 180 followed by a taper (duration of taper depends on dose of ruxolitinib at Day 180). Once a patient's counts have reached ANC ≥ 1.5 K/cumm, hemoglobin ≥ 9.0 g/dL, and platelets ≥ 50 K/cumm, ruxolitinib dosing will escalate to 10 mg BID. * In addition, patients will receive abatacept 10 mg/kg IV over 30 minutes on days +5, +14, +28, and +56.

Group II: Regimen 1: Ruxolitinib Experimental Treatment 1 Intervention

-Ruxolitinib at 5 mg twice per day (BID) beginning on Day -3 and continuing until Day 180 followed by a taper (duration of taper depends on dose of ruxolitinib at Day 180). Once a patient's counts have reached ANC ≥ 1.5 K/cumm, hemoglobin ≥ 9.0 g/dL, and platelets ≥ 50 K/cumm, ruxolitinib dosing will escalate to 10 mg BID.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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 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 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]

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]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, was approved by the FDA for treating steroid-refractory acute graft-versus-host disease (GVHD) based on promising results from the Phase II REACH1 trial.

The drug shows potential not only for treating SR acute GVHD but also for preventing GVHD and possibly serving as a first-line therapy, highlighting its versatility in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of graft-versus-host disease. Ali, H., Salhotra, A., Modi, B., et al.[2021]

In a study of 74 patients with steroid-resistant acute graft-versus-host disease (SR-aGVHD) treated with ruxolitinib, the treatment led to satisfactory outcomes, particularly with elevated levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) indicating a positive response.

Ruxolitinib enhances the function of PMN-MDSCs through specific signaling pathways, including JAK/STAT and ROS-MAPK/NF-κB, suggesting that monitoring MDSC levels could be a useful way to evaluate treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK1/2 inhibitor ruxolitinib promotes the expansion and suppressive action of polymorphonuclear myeloid-derived suppressor cells via the JAK/STAT and ROS-MAPK/NF-κB signalling pathways in acute graft-versus-host disease. Cao, Y., Wang, J., Jiang, S., et al.[2023]

Ruxolitinib is a well-absorbed tyrosine kinase inhibitor with 95% bioavailability, primarily metabolized in the liver, and its pharmacokinetics can vary based on factors like gender and body weight.

The drug's effectiveness can be influenced by liver and renal function, necessitating dose adjustments, and while model-informed precision dosing could enhance treatment personalization, more research is needed before it can be routinely implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. Appeldoorn, TYJ., Munnink, THO., Morsink, LM., et al.[2023]

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]

Citations

1. hcp.jakafi.com hcp.jakafi.com/acute-graft-versus-host-disease/efficacy-reach2-efficacy

Efficacy in Phase 3 REACH2 Study Grade 2 patients on Jakafi (ruxolitinib) had ~3x higher ORR. 1 REACH2: For all grades studied, ORRs at day 28 were higher with Jakafi vs control therapy.

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

Ruxolitinib treatment outcomes in acute graft-versus-host ... The three-year OS was 64.1% (95% CI: 48.2–76.3). Ruxolitinib appears effective and safe in real-world practice. The presented data is in line with the results ...

3. 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 ... Overall survival and progression-free survival at 2 years were 76% and 68%, respectively. Prolonged administration of ruxolitinib following HCT ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2033122

Ruxolitinib for Glucocorticoid-Refractory Chronic Graft- ... As of the data cutoff, 31 patients (18.8%) who received ruxolitinib and 27 patients (16.5%) who received control therapy had died. Deaths were ...

5. nature.com nature.com/articles/s41409-024-02252-z

Ruxolitinib for the treatment of acute and chronic graft ... Ruxolitinib, a selective JAK 1–2 inhibitor, showed promising results in the treatment of SR-GvHD in adult trial, including patients >12 years old.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11358232/

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.