Fostamatinib Disodium in Preventing Chronic Graft Versus Host Disease in Patients with Hematologic Malignancies after Donor Stem Cell Transplant

Inclusion Criteria

• Patients who have undergone allogeneic stem cell transplantation for the treatment of any hematological malignancy are eligible
• Peripheral blood stem cells, bone marrow, or umbilical cord blood may be used as the stem cell source
• Patients must have received transplantation from an human leukocyte antigen (HLA)-matched (6/6 loci at A, B, and DRB1) or mismatched (3-5/6) donor (related or unrelated); class I and II typing is to be performed by standard methods at our institution
• Patients who have undergone a non-myeloablative stem cell transplant must have > 65% donor lymphoid hematopoiesis within 30 days of study enrollment
• Patients without cGVHD are defined as having no signs or symptoms of GVHD with chronic features diagnosed at any time prior to enrollment
• In patients without cGVHD, transplant must have occurred 80-150 days before the start of study drug
• Patients with steroid refractory chronic GVHD are defined as having persistent signs and symptoms of chronic GVHD despite the use of prednisone at >= 0.5 mg/kg/day for at least 2 weeks in the preceding 24 months (or equivalent doses of alternate corticosteroids) without complete resolution of signs and symptoms
• Patients with steroid refractory chronic GVHD must be on stable doses of corticosteroids and other immunosuppressive medications for 2 weeks prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Karnofsky performance status (KPS) >= 60
• Must be able to tolerate routine oral voriconazole, posaconazole or isavuconazole as fungal prophylaxis therapy
• Written informed consent

Exclusion Criteria

• Participation in a clinical trial evaluating another preventative or treatment strategy for chronic GVHD or ongoing participation in a clinical trial for therapy of acute GVHD; prior completion of experimental therapy for acute GVHD is permissible if the experimental agent was used > 30 days prior to enrollment
• Evidence of any active uncontrolled infection (bacterial, viral or fungal) or evidence of natural exposure to hepatitis B, hepatitis C or human immunodeficiency virus (HIV) without demonstration of polymerase chain reaction (PCR) negativity for said virus; vaccination to hepatitis B is not an exclusion criterion
• Any evidence of ongoing gastrointestinal or hepatic acute GVHD or evidence of greater than ongoing stage I cutaneous acute GVHD at time of enrollment; ongoing, tapering therapy for resolved acute GVHD is permissible
• Patients with steroid refractory cGVHD cannot have prior exposure to any new immunosuppressive medication in the preceding 2 weeks prior to enrollment
• Patients with steroid refractory cGVHD cannot have history of the following therapies at any time in the post-transplant period: B-cell depleting biologic agents within the past 18 months, BTK/SYK/JAK/PI3K inhibitors within the past 2 weeks, CD19 chimeric antigen receptor (CAR) T-cell therapies at any time post-transplant
• Patients may have received no more than one donor lymphocyte infusion (DLI), DLI must have been administered > 6 weeks prior to enrollment on study, and no plans for a DLI in the upcoming 30 days
• Any major cardiovascular event within 6 months of study initiation, including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, pulmonary embolism, heart failure uncontrolled by medications or New York Heart Association class III or IV heart failure
• Uncontrolled or poorly controlled hypertension, defined as systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg, whether or not the subject is receiving anti-hypertensive treatment; subjects may be rescreened if the blood pressure is successfully and promptly controlled within 5 days using conventional anti-hypertensive therapy to achieve optimal blood pressure control (< 140/90 mmHg)
• Active hemolytic anemia
• Arterial or venous thrombosis requiring active anticoagulation; (if a patient has a history of arterial or venous thrombosis and has completed anticoagulation therapy, then he/she is not excluded)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3.0 x upper limit of normal (ULN)
• Total bilirubin > 1.5 x ULN
• Alkaline phosphatase > 2.5 x ULN
• Neutrophil count < 1.5 x 10^9/L or platelet count < 75 x 10^9/L
• Pregnancy or lactation