Ruxolitinib treatment for acute graft-versus-host disease

Phase 2 Study of Ruxolitinib-Based Primary Treatment for Acute GVHD

This study is testing if ruxolitinib can help people with acute graft-versus-host disease who haven't improved with regular steroid treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 98 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (other)
• Drugs / interventions: ruxolitinib, prednisone
• Locations: 14 sites (Duarte, California and 13 other locations)
• Trial ID: NCT06936566 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of ruxolitinib, a JAK inhibitor, for treating acute graft-versus-host disease (GVHD) that occurs after allogeneic hematopoietic cell transplantation. The study aims to evaluate the effectiveness of ruxolitinib in patients who have not responded to standard steroid treatments. Participants will be classified into standard and high-risk cohorts based on the Minnesota risk system, which predicts responses to treatment. The trial will assess the safety and efficacy of ruxolitinib in managing symptoms of GVHD, which can include skin rash, jaundice, nausea, vomiting, and diarrhea.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with newly diagnosed acute GVHD classified as either standard or high risk according to the Minnesota risk system.

Not a fit: Patients who have previously received systemic treatment with ruxolitinib or other JAK inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from acute GVHD, potentially improving their outcomes and quality of life.

How similar studies have performed: Other studies have shown promising results with JAK inhibitors in treating GVHD, indicating that this approach may be effective.

Eligibility criteria

Inclusion Criteria:

* Standard risk cohort: Minnesota standard risk GVHD (except patients with grade I \[\<50% BSA rash\])
* High risk cohort: Minnesota high risk GVHD 3 GVHD that developed after DLI for mixed chimerism or poor graft function is allowed
* No prior systemic acute GVHD treatment. Topical or non-absorbed steroids are permitted.
* All donor types, HLA-matches, conditioning regimens, or GVHD prophylaxis strategies are acceptable
* ≥18 years of age
* Standard risk cohort: Hematopoietic engraftment with absolute neutrophil count (ANC) ≥ 1000/μL and platelet count ≥20,000. Use of growth factor supplementation and transfusions to maintain adequate hematologic parameters are allowed.
* High risk cohort: Hematopoietic engraftment with ANC ≥ 500/uL and platelet count ≥20,000. Use of growth factor supplementation and transfusions to maintain adequate hematologic parameters are allowed.

Exclusion Criteria:

* Systemic treatment with ruxolitinib or any other JAK inhibitor within 7 days of study entry
* Prior use of ruxolitinib to treat GVHD at any time
* Relapsed, progressing or persistent malignancy requiring withdrawal of systemic immunosuppression
* Relapse prior to development of GVHD unless subsequently in remission for at least 3 months
* GVHD that developed after DLI for relapse is not allowed without study PI or medical monitor approval
* Uncontrolled infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis)
* Severe organ dysfunction within 3 days of enrollment including requirement for dialysis, mechanical ventilation, continuous BiPAP, or continuous high flow oxygen by nasal cannula, or total bilirubin ≥ 3x upper limit of normal not due to GVHD.
* A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment (except for mild oral or ocular GVHD)
* Corticosteroids \>10 mg/day methylprednisolone (or other methylprednisolone equivalent, MPE) for any indication within 5 days before the onset of acute GVHD except for adrenal insufficiency or premedication for transfusions/IV meds
* Participation in clinical trials using experimental agents not approved by the FDA for any indication within 14 days of enrollment or five half-lives, whichever is longer provided any prior adverse events have improved to ≤grade 1
* Patients who are pregnant or nursing
* History of allergic reaction to ruxolitinib or any JAK inhibitor

Where this trial is running

Duarte, California and 13 other locations

• City of Hope Comprehensive Cancer Center — Duarte, California, United States (RECRUITING)
• Moffitt Cancer Center — Tampa, Florida, United States (NOT_YET_RECRUITING)
• Winship Cancer Institute, Emory University — Atlanta, Georgia, United States (RECRUITING)
• Kansas University Medical Center — Fairway, Kansas, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• Mayo Clinic — Rochester, Minnesota, United States (RECRUITING)
• Washington University — St Louis, Missouri, United States (NOT_YET_RECRUITING)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (RECRUITING)
• Ohio State University — Columbus, Ohio, United States (NOT_YET_RECRUITING)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (NOT_YET_RECRUITING)
• Vanderbilt University — Nashville, Tennessee, United States (RECRUITING)
• MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• Fred Hutchinson Cancer Research Center — Seattle, Washington, United States (RECRUITING)

Study contacts

• Principal investigator: John Levine, MD, MS — Icahn School of Medicine at Mount Sinai
• Study coordinator: Rachel Young, BA

Conditions: Acute Graft-versus-host Disease, Allogeneic Bone Marrow Transplantation, Adverse Effects