Study of Efficacy and Safety of Ruxolitinib in Chinese Participants With Corticosteroid-refractory Chronic Graft vs. Host Disease

A Single-arm Multi-center Study of Ruxolitinib in Chinese Participants With Corticosteroid-refractory Chronic Graft Versus Host Disease After Allogeneic Stem Cell Transplantation

The purpose of the study is to assess the efficacy and safety of ruxolitinib in Chinese adult and pediatric participants aged 12 years or older with corticosteroid-refractory chronic graft vs. host disease (SR-cGvHD).

This is a single arm, multi-center, open label study which will enroll approximately 50 participants and investigate the efficacy and safety of ruxolitinib administered in adult and adolescent (≥12 years old) Chinese participants with SR-cGvHD.

The total duration on study for an individual participant will be up to 164 weeks (approximately 3 years).

The study consists of following periods, with each cycle comprised of 4 weeks (28 days):

• Screening Period (Day -28 to Day -1)
• Treatment period (Day 1 to Cycle 39/EOT)
• Safety follow-up (Last dose +30 days)
• Long-term survival follow-up period (EOT to 156 weeks on study).

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.

• Male or female Chinese participants aged 12 or older at the time of informed consent

• Able to swallow tablets.- 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.

• Evident myeloid and platelet engraftment:

  • Absolute neutrophil count (ANC) >1,000/mm3 AND
  • Platelet count ≥25,000/mm3

Note: Use of growth factor supplementation and transfusion support is allowed during the trial, however, transfusion to reach a minimum platelet count for inclusion is not allowed during screening and at baseline.

• Participants with clinically diagnosed cGvHD staging of moderate to severe according to NIH Consensus Criteria (Jagasia et al 2015) prior to Cycle 1 Day 1.

  • 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 corticosteroids for the treatment of cGvHD for a duration of < 12 months prior to Cycle 1 Day 1, and have a confirmed diagnosis of corticosteroid refractory cGvHD defined per 2014 NIH consensus criteria (Martin et al 2015) irrespective of the concomitant use of a calcineurin inhibitor, as follows:

  • A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week (or equivalent) 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 equivalent) OR
  • Increase to prednisone dose to >0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent)

• Participants has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

For a full list of exclusion criteria, refer to Section 5.2. Key exclusion criteria include

• Participants who have received two or more systemic treatments for cGvHD in addition to corticosteroids ± CNI for cGvHD.
• Participants who have received ROCK2 inhibitors for cGvHD.
• Participants that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment

Note: Participants 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.
• SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive 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.

Other protocol-defined inclusion/exclusion may apply.