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.
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: 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
Parallel
Best Practice
Other interventionReceive SOC treatment
Biomarker Analysis
Other interventionUndergo GHVD biomarker analysis
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Questionnaire Administration
Other interventionAncillary studies
Ruxolitinib
DrugGiven PO
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.
Chronic graft versus host disease (cGVHD) (Expansion cohort)
Will be evaluated and scored according to National Institutes of Health (NIH) Consensus Staging.
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.
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.
Overall survival
Will be evaluated in all patients (those who receive ruxolitinib as pre-emptive therapy and those who did not receive ruxolitinib due to low levels of blood biomarkers). Patients are considered a failure for this endpoint if they die, regardless of cause. Will be censored at last follow-up if the last known status is alive. Will be analyzed using the Kaplan-Meier curves.
Immunosuppression-free survival
Patients are considered failure to this endpoint if they die (regardless of cause) or need immunosuppression (for any reason including acute or cGVHD development). Immunosuppression-free survival will be censored at last follow-up if the last known status is alive and free of immunosuppression drug usage. Will be analyzed using the Kaplan-Meier curves.
Relapse
Deaths without relapse/progression are considered a competing risk event. Surviving patients with no history of relapse/progression are censored at time of last follow-up. Will be analyzed using the Kaplan-Meier curves.
Non-relapse mortality
Non-relapse mortality is defined as death occurring in a patient from causes other than relapse or progression. Will be censored at last follow-up if patients are alive and remain disease free. Will be analyzed using the Kaplan-Meier curves.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
