NCT07025538

Biomarker-Guided Ruxolitinib for the Prevention of Chronic Graft Versus Host Disease After Allogeneic Hematopoietic Cell Transplantation

Biomarker-Guided Feasibility/Efficacy Trial of Ruxolitinib in Patients With High-Risk of Chronic Graft-Versus-Host Disease Development After Allogeneic Hematopoietic Cell Transplantation

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies how well biomarker-guided ruxolitinib works for the prevention of chronic graft versus host disease (GVHD) in patients that have undergone allogeneic hematopoietic cell transplant (HCT). Allogeneic HCT is the most effective therapy for patients with high-risk blood and bone marrow malignancies. GVHD is a disease caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Symptoms include jaundice, skin rash or blisters, a dry mouth, or dry eyes. In chronic GVHD (cGVHD), symptoms occur more than three months after transplantation. Despite significant advances in how allogeneic HCTs are conducted, cGHVD remains a major limitation to the long-term success of the transplant and can impact patients' quality of life post-transplant. Checking GVHD biomarkers in patients' blood after allogeneic HCT may help doctors predict how likely the patient is to develop cGVHD. This information can be used to help guide patients with high levels to receive cGVHD preventative therapy with ruxolitinib. Ruxolitinib works by blocking some of the enzymes that are needed for the development of cGVHD, which may be an effective way to prevent cGVHD in patients with high levels of GVHD biomarkers.

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety and feasibility of ruxolitinib administration in patients with elevated levels of chronic GVHD biomarkers at day +100 after allogeneic hematopoietic cell transplantation (HCT). (Safety lead-in) II. Evaluate the efficacy of ruxolitinib in preventing chronic GVHD by assessing 1-year moderate-to-severe cGVHD-free survival (CGFS) defined as first occurrence of moderate to severe chronic GVHD or death, whichever occurs first, after the first dose of ruxolitinib. (Expansion cohort) SECONDARY OBJECTIVES: I. Assess the overall survival (OS) at 1 and 2 years from enrollment and immunosuppression-free survival at 1-year from enrollment. II. Estimate cumulative incidence of relapse and non-relapse mortality (NRM) at 1 and 2 years from enrollment. III. Cumulative incidence and grading of chronic GVHD of all grades and moderate-to severe at 1 and 2 years from enrollment. IV. Preliminary estimate of chronic GVHD-free and relapse-free (CRFS) at 1-year post-enrollment. V. Cumulative incidence of severe infections requiring hospitalization at 1 and 2 years from enrollment. VI. Quality of life assessment using Patient-Reported Outcomes Measurement Information System Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). VII. Further evaluation of safety of ruxolitinib for chronic GVHD prophylaxis. (Patients in the expansion cohort who are taking ruxolitinib only) EXPLORATORY OBJECTIVES: I. Assess levels of chronic GVHD biomarkers and other inflammatory cytokines at 6 months and 1-year post-HCT and correlate elevated levels of serum/plasma biomarkers of chronic GVHD with pre-HCT risk factors for GVHD and subsequent development of GVHD. II. Longitudinal evaluation of the presence and levels of T cells and other immune cell subsets. III. Assess changes in microbiome from the time of screening to 3 months after enrolment and at the time of cGVHD diagnosis. OUTLINE: Patients undergo blood sample collection and GHVD biomarker analysis on day +100 post-HCT. Patients with elevated levels of GVHD biomarkers are assigned to arm I and patients with low levels of GVHD biomarkers are assigned to arm II. ARM I: Starting between days +105 and +130 post-HCT, patients receive ruxolitinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo additional blood sample collection throughout the trial. ARM II: Starting between days +105 and +130 post-HCT, patients receive standard of care (SOC) treatment for up to 1 year in the absence of disease progression or unacceptably toxicity. Patients also undergo additional blood sample collection throughout the trial. After completion of study treatment, patients in arm I are followed up at 30 days, months 15, 18, and 24, and at the time of cGVHD diagnosis, if applicable. Patients in arm II are followed up at months 18 and 24 and at the time of cGVHD diagnosis, if applicable.

Conditions

• Hematopoietic and Lymphatic System Neoplasm

Interventions

Type	Name	Description
OTHER	Best Practice	Receive SOC treatment
OTHER	Biomarker Analysis	Undergo GHVD biomarker analysis
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Ruxolitinib	Given PO

Timeline

• Start date: 2026-03-09
• Primary completion: 2029-06-22
• Completion: 2029-06-22
• First posted: 2025-06-17
• Last updated: 2026-02-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study