A Study of Ruxolitinib vs Best Available Therapy (BAT) in Patients With Steroid-refractory Chronic Graft vs. Host Disease (GvHD) After Bone Marrow Transplantation (REACH3)
Condition: Graft-versus-host Disease (GVHD)
MeSH terms: Graft vs Host Disease
Intervention: Ruxolitinib; Extracorporeal photopheresis (ECP); Low-dose methotrexate (MTX); Mycophenolate mofetil (MMF); mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus); Infliximab; Rituximab; Pentostatin; Imatinib; Ibrutinib
Intervention description: Ruxolitinib twice daily at the protocol-defined starting dose.; Best available therapy (BAT) will be selected by the investigator for each participant. BAT may not include experimental agents (ie, those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. The BAT in this study will be among the following treatments currently used in this setting (no other types or combinations of BATs are permitted in this study).; Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.; Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.; Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.; Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.; Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.; Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.; Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.; Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Intervention MeSH terms: Mycophenolic Acid; Sirolimus; Infliximab; Rituximab; Methotrexate; Everolimus; Imatinib Mesylate; Pentostatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 330.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Graft-versus-host disease (GvHD); Chronic GvHD (cGvHD); steroid-refractory; ruxolitinib; Janus kinase inhibitor

Summary:

      The purpose of this study is to assess the efficacy of ruxolitinib against best available
      therapy in participants with steroid-refractory chronic graft-versus-host disease (SR cGvHD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have undergone allogeneic stem cell transplantation (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

          -  Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) > 1000/mm^3
             and platelet count > 25,000/ mm^3

          -  Participants with clinically diagnosed moderate to severe cGvHD according to NIH
             Consensus Criteria prior to randomization:

               -  Moderate cGvHD: At least one organ (not lung) with a score of 2, 3 or more organs
                  involved with a score of 1 in each organ, or lung score of 1

               -  Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3

          -  Participants currently receiving systemic or topical corticosteroids for the treatment
             of cGvHD for a duration of < 12 months prior to Cycle 1 Day 1 (if applicable), and
             have a confirmed diagnosis of steroid-refractory cGvHD defined per 2014 NIH consensus
             criteria irrespective of the concomitant use of a calcineurin inhibitor (CNI), as
             follows:

               -  A lack of response or disease progression after administration of minimum
                  prednisone 1 mg/kg/day for at least 1 week, OR

               -  Disease persistence without improvement despite continued treatment with
                  prednisone at > 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, OR

               -  Increase to prednisolone dose to > 0.25 mg/kg/day after 2 unsuccessful attempts
                  to taper the dose

          -  Participant must accept to be treated with only one of the following BAT options on
             Cycle 1 Day 1 (additions and changes are allowed during the course of the study, but
             only with BAT from the following BAT options): extracorporeal photopheresis (ECP),
             low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus
             or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib

        Exclusion Criteria:

          -  Participants who have received 2 or more systemic treatment for cGvHD in addition to
             corticosteroids ± CNI for cGvHD

          -  Patients that transition from active aGvHD to cGvHD without tapering off
             corticosteroids ± CNI and any systemic treatment

             * Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e.,
             physiologic replacement dose) of corticosteroids are allowed.

          -  Participants who were treated with prior JAK inhibitors for aGvHD; except when the
             participant achieved complete or partial response and has been off JAK inhibitor
             treatment for at least 8 weeks prior to Cycle 1 Day 1

          -  Failed prior alloSCT within the past 6 months from Cycle 1 Day 1

          -  Participants with relapsed primary malignancy, or who have been treated for relapse
             after the alloSCT was performed

          -  Steroid refractory cGvHD occurring after a non-scheduled donor lymphocyte infusion
             (DLI) administered for preemptive treatment of malignancy recurrence. Participants who
             have received a scheduled DLI as part of their transplant procedure and not for
             management of malignancy relapse are eligible

          -  Any corticosteroid therapy for indications other than cGvHD at doses > 1 mg/kg/day
             methylprednisolone or equivalent within 7 days of Cycle 1 Day 1