Clinical trial NCT06462469: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Steroid-refractory Acute Graft Versus Host Disease
Keywords: SR-aGvHD
aGvHD
acute graft-versus-host disease
ruxolitinib
Chinese patients
corticosteroid-refractory
Grade II-IV
Grade II to IV
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-06-17
Enrollment: 54
Sex: ALL
Minimum age (years): 12
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Key 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 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:

  1. Progression 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 to IV aGvHD. OR
  2. 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 to IV. OR
  3. Participants 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 of 7 days.

Key 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

Primary outcomes:
measure: Overall Response Rate (ORR) at Day 28 per Investigators
timeFrame: Day 28
Secondary outcomes:
measure: Durable Overall response rate (ORR) at Day 56
timeFrame: Day 56
measure: Duration of Response (DOR)
timeFrame: From Week 1 to long term follow up Month 12
measure: Best overall response (BOR)
timeFrame: From week 1 to Day 28
measure: Overall survival (OS)
timeFrame: From the date of start of study treatment to date of death, up to approx. 12 months
measure: Non-relapse mortality (NRM)
timeFrame: From date of start of study treatment to date of death, up to approx. 12 months
measure: Event-free survival (EFS)
timeFrame: 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
measure: Failure-free survival (FFS)
timeFrame: 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
measure: Malignancy Relapse/Progression (MR)
timeFrame: From date of start of study treatment to hematologic malignancy relapse/progression, up to approx. 12 months
measure: Reduction of daily corticosteroids dose
timeFrame: Up to Day 56
measure: Cumulative incidence of chronic GvHD
timeFrame: From Week 1 to long term follow up of month 12
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Zhengzhou
country: China
facility: Novartis Investigative Site
state: Henan
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Dalian
country: China
facility: Novartis Investigative Site
city: Fuzhou
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Taian
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: