Clinical trial NCT06824103: Study of Efficacy and Safety of Ruxolitinib in Chinese Participants With Corticosteroid-refractory Chronic Graft vs. Host Disease
Official title: A Single-arm Multi-center Study of Ruxolitinib in Chinese Participants With Corticosteroid-refractory Chronic Graft Versus Host Disease After Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Graft vs. Host Disease
Chronic Graft vs. Host Disease
Corticosteroid-refractory Chronic Graft vs. Host Disease
Keywords: cGvHD
GvHD
SR-cGvHD
ruxolitinib
INC424
Chinese adult
Pediatric
Corticosteroid
refractory
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2025-02-13
Enrollment: 50
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 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).

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Cycle 7 Day 1; each Cycle =28 days
Secondary outcomes:
measure: Failure-free Survival (FFS)
timeFrame: up to 3 years
measure: Best Overall Response (BOR)
timeFrame: at any point up to cycle 7 day 1 (each cycle is 28 days) or the start of additional systemic therapy for cGvHD, approx. 6 months
measure: ORR at end of cycle 3
timeFrame: end of cycle 3; each cycle = 28 days
measure: Duration of Response (DOR)
timeFrame: from first response until cGvHD progression, death, or the date of addition of systemic therapies for cGvHD, approx.36 months
measure: Overall Response (OS)
timeFrame: from the date of study treatment (ruxolitinib) initiation to the date of death due to any cause, approx. 36 months
measure: Non-Relapse Mortality (NRM)
timeFrame: from date of study treatment (ruxolitinib) initiation to date of death not preceded by underlying disease relapse/recurrence, approx. 36 months
measure: Malignancy Relapse/Recurrence (MR)
timeFrame: from date of study treatment to hematologic malignancy relapse/recurrence, approx. 36 months
measure: Reduction of daily corticosteroids dose at cycle 7 day 1
timeFrame: Cycle 7 Day 1; each cycle = 28 days
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: