Study of Efficacy and Safety of Ruxolitinib in Patients With Grade II to IV Steroid-refractory Acute Graft vs. Host Disease

Official title

A Single-arm, Multi-center Study of Ruxolitinib for the Treatment of Chinese Patients With Grade II-IV Corticosteroid-refractory Acute Graft Versus Host Disease

Overview

The purpose of this study is to assess the efficacy and safety of ruxolitinib therapy in Chinese adults and adolescents (≥ 12 years old) with Grade II-IV steroid-refractory acute graft versus host disease (SR-aGvHD).

Detailed description

Participants will start with a screening period to assess the eligibility; only participants who meet all the inclusion and none of the exclusion criteria will start study treatment from Day 1 to Week 24 or end of treatment. Following safety follow up visits, participants will receive the long-term follow-up until Month 12.

Interventions

• Drug Ruxolitinib
  Ruxolitinib is taken orally daily at 10 mg BID, given as two 5-mg tablets.

Primary outcome measures

• Overall Response Rate (ORR) at Day 28 per Investigators [Time frame: Day 28]

Secondary outcome measures (10)

• Durable Overall response rate (ORR) at Day 56 [Time frame: Day 56]
• Duration of Response (DOR) [Time frame: From Week 1 to long term follow up Month 12]
• Best overall response (BOR) [Time frame: From week 1 to Day 28]
• Overall survival (OS) [Time frame: From the date of start of study treatment to date of death, up to approx. 12 months]
• Non-relapse mortality (NRM) [Time frame: From date of start of study treatment to date of death, up to approx. 12 months]
• Event-free survival (EFS) [Time frame: From the date of start of study treatment to the date of hematologic disease relapse/progression, graft failure, or death, up to approx. 12 months]
• Failure-free survival (FFS) [Time frame: From the date of start of study treatment to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment, up to approx. 12 months]
• Malignancy Relapse/Progression (MR) [Time frame: From date of start of study treatment to hematologic malignancy relapse/progression, up to approx. 12 months]
• Reduction of daily corticosteroids dose [Time frame: Up to Day 56]
• Cumulative incidence of chronic GvHD [Time frame: From Week 1 to long term follow up of month 12]

Eligibility criteria

Inclusion criteria

• Male or female Chinese participants aged 12 or older at the time of informed consent. Written informed consent from participant, parent or legal guardian.
• 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.
• Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy.
• Evident myeloid and platelet engraftment (confirmed within 48 hours prior to study treatment (ruxolitinib) start):
• Confirmed diagnosis of steroid refractory aGvHD defined as participants administered systemic corticosteroids (methylprednisolone at least 1 mg/kg/day \[or equivalent prednisone dose at least 1.25 mg/kg/day\]), given alone or combined with calcineurin inhibitors (CNI) and either:

• Progression based on organ assessment after at least 3 days compared to organ stage at the time of initiation of systemic corticosteroid +/- CNI for the treatment of Grade II to 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 systemic corticosteroid +/-CNI for the treatment of Grade II to IV. OR
• Participants who fail corticosteroid taper defined as fulfilling either one of the following criteria:

• Requirement for an increase in the corticosteroid dose to methylprednisolone ≥ 1 mg/kg/day (or equivalent prednisone dose ≥ 1.25 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 of 7 days.

Exclusion criteria

• Has received more than one systemic treatment for steroid refractory aGvHD. Participants who received JAK inhibitor therapy for any indication after initiation of current alloSCT conditioning.
• Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features.
• Failed prior alloSCT within the past 6 months. Presence of relapsed primary malignancy after the alloSCT was performed.
• Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
• SR-aGvHD occurring after non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
• Presence of significant respiratory disease, severely impaired renal function, clinically significant or uncontrolled cardiac disease, unresolved cholestatic and liver disorders (not attributable to aGvHD). Disorders and/or current therapy with medications that interfere with coagulation or platelet function.

Other protocol-defined inclusion / exclusion criteria may apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 17 centers

• Novartis Investigative Site — Guangzhou
• Novartis Investigative Site — Guangzhou
• Novartis Investigative Site — Zhengzhou
• Novartis Investigative Site — Wuhan
• Novartis Investigative Site — Changchun
• Novartis Investigative Site — Xian
• Novartis Investigative Site — Chengdu
• Novartis Investigative Site — Hangzhou
• … and 9 more centers

Identifiers

NCT: NCT06462469 · CINC424C2416

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗