A Phase III Randomized Open-label Multi-center Study of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation (REACH 2) (CINC424C2301)

* Male or female patients aged 12 or older
* Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non- myeloablative, myeloablative, and reduced intensity conditioning are eligible
* Clinically diagnosed Grades II to IV acute GvHD as per standard criteria (Appendix 1) occurring after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
* Evident myeloid and platelet engraftment (confirmed within 48h prior to study treatment start):
o absolute neutrophil count (ANC) > 1000/mm3 AND
o platelets * 20,000/ mm3
o Note: Use of growth factor supplementation and transfusion support is allowed.
* Confirmed diagnosis of steroid refractory aGvHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:
o A] Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic steroid +/- CNI for the treatment of Grade II-IV aGvHD,
o OR B] Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic steroid +/- CNI for the treatment of Grade II-IV aGvHD,
o OR C] Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria: 1. Requirement for an increase in the corticosteroid dose to methylprednisolone *2 mg/kg/day (or equivalent prednisone dose *2.5 mg/kg/day), OR 2. Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum 7 days;see also section 5.2 in protocol

1. Has received more than one systemic treatment for steroid refractory aGvHD.
2. Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features (as defined by Jagasia, et al. 2015).
3. Failed prior alloHSCT within the past 6 months.
4. Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
5. Evidence of uncontrolled viral infection including CMV, EBV, HHV-6, HBV, or HCV based on assessment by the treating physician.
6. Presence of relapsed primary malignancy, or who have been treated for relapse after the alloHSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of
early malignancy relapse.
7. Previous participation in a study of any investigational treatment agent within 30 days of Screening or within 5 half-lives of the study treatment, whichever is greater.;see also protocol section 5.3