Biomarker-Guided Feasibility/Efficacy Trial of Ruxolitinib in Patients With High-Risk of Chronic Graft-Versus-Host Disease Development After Allogeneic Hematopoietic Cell Transplantation
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: 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
• PRE-SCREENING: Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (to be performed between day +70 and +100 after HCT unless otherwise stated)
• PRE-SCREENING: Aspartate aminotransferase (AST) =\< 3.0 x ULN (to be performed between day +70 and +100 after HCT unless otherwise stated)
• PRE-SCREENING: Alanine aminotransferase (ALT) =\< 3.0 x ULN (to be performed between day +70 and +100 after HCT unless otherwise stated)
• PRE-SCREENING: Glomerular filtration rate (GFR) ≥ 50 ml/min (to be performed between day +70 and +100 after HCT unless otherwise stated)
• PRE-SCREENING: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed between day +70 and +100 after HCT unless otherwise stated)
⁃ If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• PRE-SCREENING: Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
⁃ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): Documented informed consent of the participant and/or legally authorized representative
⁃ Assent, when appropriate, will be obtained per institutional guidelines
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): Elevated serum/plasma levels of ST2, CXCL9, MMP-3, and OPN as indicated by moderate or severe risk of chronic GVHD in the test results
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): No use of ruxolitinib or other Jak inhibitors in the past 14 days
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): Morphologic remission per day +100 bone marrow
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): Adequate hematopoietic recovery (hemoglobin \[Hgb\] ≥ 8 g/dL, platelets \[PLT\] ≥ 50K/ mm\^3)
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): Negative serum or urine pregnancy test (female participants with childbearing potential only)
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): Absence of active infection not responding to antibiotics
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): Absence of progressive acute GVHD. Note: prednisone administration (flat dose of \< 0.25 mg/kg) is allowed. Patients receiving any other medication to control active/progressive GVHD will be excluded
• AFTER DAY +100 TEST RESULTS PATIENTS WITH MODERATE TO HIGH-RISK cGVHD (TREATMENT ARM): Absence of any clinically significant uncontrolled sickness
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): Documented informed consent of the participant and/or legally authorized representative
⁃ Assent, when appropriate, will be obtained per institutional guidelines
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): Low serum/plasma levels of ST2, CXCL9, MMP-3, and OPN as indicated by low risk of chronic GVHD in the test results
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): No use of ruxolitinib or other Jak inhibitors in the past 14 days
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): Morphologic remission per day +100 bone marrow
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): Adequate hematopoietic recovery (Hgb ≥ 8 g/dL, PLT ≥ 50K/ mm\^3)
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): Negative serum or urine pregnancy test (female participants with childbearing potential only)
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): Absence of active infection not responding to antibiotics
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): Absence of progressive acute GVHD. Note: prednisone administration (flat dose of \< 0.25 mg/kg) is allowed. Patients receiving any other medication to control active/progressive GVHD will be excluded
• AFTER DAY +100 TEST RESULTS PATIENTS WITH LOW-RISK cGVHD (CONTROL ARM): Absence of any clinically significant uncontrolled sickness