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

NCT07025538 | Suspended Phase 1 DMC FDA Drug

• 3 other identifiers: 24752NCI-2025-03045P30CA033572
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hematopoietic and Lymphatic System Neoplasm

Outcome Measures

Primary Outcomes (5)

• Incidence of unacceptable toxicity (UT) (Safety lead-in segment)

  UT in a given patient will be defined as any of the following that are assigned an attribution level of at least possibly related to ruxolitinib administration. 1) Any grade 3 or higher non-hematological adverse events, per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 toxicity criteria that last more than 5 days. 2) Prolonged myelosuppression, defined as ≥ grade 4 neutropenia or thrombocytopenia that persists for more than 7 days. 3) Hy's law cases. 4) Any other regimen-related cause of death. 5) Permanent discontinuation or dose reduction of ruxolitinib due to any drug-related toxicity (regardless of grade). In addition, septic UT is defined as: any grade 5 sepsis-related toxicity that is assigned an attribution level of at least possibly related to the addition of ruxolitinib to the conditioning regimen.

  From first dose of ruxolitinib to end of first cycle (Cycle length = 28 days)

• Chronic graft versus host disease (cGVHD) (Expansion cohort)

  Will be evaluated and scored according to National Institutes of Health (NIH) Consensus Staging.

  Up to 1 year post first dose of ruxolitinib

• Moderate-to-severe cGVHD free survival (GFS)

  GFS will be censored at the last follow-up if patients are alive and remain free of moderate-to-severe cGVHD. GFS will be assessed in both the safety lead-in segment and expansion cohort. Will be analyzed using the Kaplan-Meier curves.

  From date of starting first dose of ruxolitinib to first occurrence of moderate-to-severe cGVHD or death, whichever occurs first, assessed up to 12 months post first dose of ruxolitinib

• Patients completing at least 80% of planned ruxolitinib (Feasibility) (Expansion cohort)

  Patients who take at least one dose of ruxolitinib will be evaluable for feasibility. The point estimate and exact 95% confidence intervals (CIs) will be provided.

  Up to 1 cycle of ruxolitinib (Cycle length = 28 days)

• Tolerability of ruxolitinib (Expansion cohort)

  Patients who have ruxolitinib dose interruption, reduction, or early stopping due to adverse events attributable to ruxolitinib are deemed to be intolerable to ruxolitinib.

  Up to 12 cycles (Cycle length = 28 days)

Secondary Outcomes (12)

• Overall survival

  From enrollment to death, assessed at 1 and 2 years post-enrollment

• Immunosuppression-free survival

  From the date of enrollment to the date of death, use of immunosuppressive agents, whichever occurs first, assessed at 1 year post-enrollment

• Relapse

  From day of enrollment to first observation of disease relapse/progression, assessed at 1 and 2 years post-enrollment

• Non-relapse mortality

  From date of stem cell infusion until non-disease related death, assessed at 1 and 2 years post-enrollment

• cGVHD

  From day 100 through 1-year and 2- years post-transplant

Study Arms (2)

Arm I (ruxolitinib)

EXPERIMENTAL

Starting between days +105 and +130 post-HCT, patients receive ruxolitinib PO 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.

Other: Biomarker Analysis; Procedure: Biospecimen Collection; Other: Questionnaire Administration; Drug: Ruxolitinib

Arm II (SOC treatment)

ACTIVE COMPARATOR

Starting between days +105 and +130 post-HCT, patients receive 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.

Other: Best Practice; Other: Biomarker Analysis; Procedure: Biospecimen Collection; Other: Questionnaire Administration

Interventions

Best Practice OTHER

Receive SOC treatment

Also known as: standard of care, standard therapy

Arm II (SOC treatment)

Biomarker Analysis OTHER

Undergo GHVD biomarker analysis

Arm I (ruxolitinib); Arm II (SOC treatment)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (ruxolitinib); Arm II (SOC treatment)

Questionnaire Administration OTHER

Ancillary studies

Arm I (ruxolitinib); Arm II (SOC treatment)

Ruxolitinib DRUG

Given PO

Also known as: INCB 018424, INCB-018424, INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424

Arm I (ruxolitinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PRE-SCREENING: Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• PRE-SCREENING: Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• PRE-SCREENING: Age: ≥ 18 years
• PRE-SCREENING: Karnofsky performance status ≥ 80
• PRE-SCREENING: Patients must have undergone allogeneic hematopoietic cell transplantation with peripheral blood stem cells as graft source. Note: Patients receiving manipulated graft are not included
• PRE-SCREENING: Morphologic remission per day +30 bone marrow
• PRE-SCREENING: Any conditioning regimen (myeloablative, reduce intensity/non-myeloablative conditioning) is allowed
• PRE-SCREENING: Any GVHD prophylaxis (tacrolimus-sirolimus, tacrolimus-methotrexate, or post-transplant cyclophosphamide) is allowed
• PRE-SCREENING: Life expectancy of more than 6 months
• PRE-SCREENING: Absolute neutrophil count (ANC) \> 1000/mm\^3 (to be performed between day +70 and +100 after HCT unless otherwise stated)
• PRE-SCREENING: Hemoglobin ≥ 8.0 gm/dL (to be performed between day +70 and +100 after HCT unless otherwise stated)
• PRE-SCREENING: Platelets ≥ 50,000/mm\^3 (to be performed between day +70 and +100 after HCT unless otherwise stated)
• Note: Patients with lower counts can enroll if infection cytomegalovirus (CMV)/human herpesvirus 6 (HHV6), etc. is being treated actively

You may not qualify if:

• PRE-SCREENING: Prior chemotherapy \< 14 days prior to study biospecimen collection on day +100 post-HCT
• PRE-SCREENING: Previous use of ruxolitinib or other JAK-inhibitors is allowed but administration should be stopped for at least 14 days prior to enrollment. Note: Previous use of Jak inhibitors before enrollment (including the pre-HCT period) should be recorded
• PRE-SCREENING: History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• PRE-SCREENING: Active/progressive acute GVHD at the time of screening. Prednisone administration (flat dose of \< 0.25 mg/kg) is allowed. Patients receiving any other medication to control active/progressive GVHD will be excluded
• PRE-SCREENING: Patients with history of major adverse cardiovascular event (MACE)/other thrombosis (myocardial infarction \[MI\]/stroke and pulmonary embolism \[PE\]/deep vein thrombosis \[DVT\]) in the past 6 months
• PRE-SCREENING: Patients with a history of tuberculosis
• PRE-SCREENING: Clinically significant uncontrolled illness
• PRE-SCREENING: Active infection not responding to antibiotics
• PRE-SCREENING: Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• PRE-SCREENING: Females only: Pregnant or breastfeeding
• PRE-SCREENING: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• PRE-SCREENING: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Interventions

Practice Guidelines as Topic; Standard of Care; Specimen Handling; ruxolitinib

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Amandeep Salhotra

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2025
• First Posted: June 17, 2025
• Study Start: March 9, 2026
• Primary Completion (Estimated): June 22, 2029
• Study Completion (Estimated): June 22, 2029
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

US (1)