Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD

Inclusion Criteria 1. Patient is able and willing to provide written informed consent prior to any study related screening procedures are performed. 2. Age ≥ 18 years old at the time of informed consent 3. Have undergone allogeneic hematopoietic cell transplantation (HCT) from any donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood, or cord blood stem cells. 4. Adequate bone marrow function defined as: 4.1 Absolute neutrophil count (ANC) ≥ 750 /mm3 4.2 Platelet count ≥ 40,000 /mm3 4.3 Hemoglobin ≥ 8.0 g/dL without transfusion support Note: Use of growth factor supplementation (myeloid, erythroid or megakaryocytic) is permitted to meet eligibility criteria. 5. Patients with clinically diagnosed cGvHD staging of mild to severe according to NIH Consensus Criteria4 prior to Cycle 1 Day 1 and with confirmed steroid refractoriness or steroid dependence irrespective of the concomitant use of a calcineurin inhibitor, as follows: 5.1 Disease progression after administration of a minimum dose of 1.0 mg/kg/day or equivalent for at least 1 week at any time following diagnosis of cGvHD OR 5.2 Disease persistence despite continued treatment with prednisone \> 0.5mg/kg/d or equivalent for at least 4 weeks OR 5.3 Increase to prednisone \> 0.25 mg/kg/d after 1 unsuccessful attempt to taper the dose. 5.4 Recurrence of chronic GVHD after attaining a complete response 5.5 Progression of chronic GVHD after attaining a partial response 6. Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Exclusion Criteria 1. Prior or ongoing treatment with ruxolitinib for treatment of cGvHD for longer than 3 weeks prior to anticipated C1D1. 2. Prior treatment with fostamatinib or another SYK inhibitor for the treatment of acute or chronic GVHD. Prior use of fostamatinib for conditions other than GVHD is permitted. 3. Ongoing systemic therapy for cGvHD other than corticosteroids, calcineurin inhibitor, or mycophenolate mofetil, aside from fewer than 3 weeks of ruxolitinib. Prior ruxolitinib use for the indication of acute GVHD is permitted. 4. Patients with relapsed primary malignancy, or who have been treated for relapse after the allogeneic HCT was performed 5. SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Patients who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible. 6. History of progressive multifocal leuko-encephalopathy (PML) 7. Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. 8. Clinical evidence of active and clinically significant viral disease including HIV, CMV, HHV-6, HBV, HCV, or BK virus. 9. Patients on mechanical ventilation or have a resting O2 saturation \< 90% by pulse oximetry 10. Clinically significant and uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 3 months, or NYHA Class III or IV congestive heart failure. 11. Uncontrolled hypertension with systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg. 12. Creatinine clearance by Cockcroft-Gault of \< 15 mL/min and not on dialysis 13. Total bilirubin \> 3 times ULN, ALT \> 5 times ULN, or AST \> 5 times ULN 14. QTc ≥ 470 ms as calculated by the Fridericia Formula 15. Active pregnancy or breast feeding, or currently seeking active pregnancy 16. Any patient who, in the opinion of the investigator, may not be able to comply with study procedures