Safety and Efficacy of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation
Condition: Corticosteroid Refractory Acute Graft vs Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Ruxolitinib (RUX); Best Available Therapy (BAT)
Intervention description: Ruxolitinib was provided as 5 mg tablets for oral use.; BAT was based on the investigator's best judgment, taking into account the manufacturer's instructions, labeling, patient's medical condition, and institutional guidelines for any dose adjustment. The BAT in this study was identified by the investigator prior to patient randomization among the following treatments currently used in this setting: anti-thymocyte globulin (ATG), extracorporeal photopheresis (ECP), mesenchymal stromal cells (MSC), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), etanercept, or infliximab. No other types or combinations of BAT were permitted.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 310.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: GvHD (Graft versus Host Disease); INC424; ruxolitinib; best available therapy (BAT); corticosteroid-refractory acute graft vs. host disease; allogeneic stem cell transplantation; steroid refractory acute graft vs. host disease; Janus Kinase (JAK) inhibitor

Summary:

      Assess the efficacy and safety of ruxolitinib compared to Best Available Therapy (BAT) in
      patients with corticosteroid-refractory acute graft vs. host disease (aGvHD) after allogeneic
      stem cell transplantation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have undergone Allogeneic Stem Cell Transplanttaion (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 occurring
             after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs
             with aGvHD is encouraged but not required for study screening.

          -  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:

               -  Progressing based on organ assessment after at least 3 days compared to organ
                  stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for
                  the treatment of Grade II-IV aGvHD, OR

               -  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
                  corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,OR

               -  Patients who fail corticosteroid taper defined as fulfilling either one of the
                  following criteria:

          -  Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2
             mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day) , OR

          -  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.

        Exclusion Criteria:

          -  Has received more than one systemic treatment for steroid refractory aGvHD.

          -  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.

          -  Evidence of uncontrolled viral infection including Cytomegalovirus (CMV), Epstein-Barr
             Virus (EBV), Human Herpes Virus-6 (HHV-6), Hepatitis Virus (HBV), or Hepatitis C Virus
             (HCV) based on assessment by the treating physician.

          -  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.