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

Steroid-refractory Acute Graft Versus Host Disease Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06462469
• Other study ID #: CINC424C2416
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 30, 2024
• Est. completion date: November 5, 2026

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +41613241111
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 54
• Est. completion date: November 5, 2026
• Est. primary completion date: April 8, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 methylpredinisolone =2 mg/kg/day (or equivalent predinisone 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

Related Conditions & MeSH terms

• Graft vs Host Disease
• Steroid-refractory Acute Graft Versus Host Disease

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) at Day 28 per Investigators	The ORR at Day 28 defined as the percentage of participants demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, mixed response or nonresponse, according to standard criteria and assessed by investigators.	Day 28
Secondary	Durable Overall response rate (ORR) at Day 56	Durable ORR at Day 56 is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) at Day 28 and maintain a CR or PR at Day 56.	Day 56
Secondary	Duration of Response (DOR)	DOR is defined as the time from first response until aGvHD progression or the date of additional systemic therapies for aGvHD.	From Week 1 to long term follow up Month 12
Secondary	Best overall response (BOR)	Percentage of participants who achieved overall response (complete response (CR) + Partial response (PR) at any time point up to and including Day 28 and before the start of additional systemic therapy for aGvHD.	From week 1 to Day 28
Secondary	Overall survival (OS)	Overall survival (OS) is defined as the time from the date of start of study treatment to date of death due to any cause.	From the date of start of study treatment to date of death, up to approx. 12 months
Secondary	Non-relapse mortality (NRM)	Non-relapse mortality (NRM) is defined as the time from date of start of study treatment to date of death not preceded by hematologic disease relapse/progression.	From date of start of study treatment to date of death, up to approx. 12 months
Secondary	Event-free survival (EFS)	Event-free survival (EFS) is defined as the time from the date of start of study treatment to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.	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
Secondary	Failure-free survival (FFS)	Failure-free survival (FFS) is defined as the time 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.	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
Secondary	Malignancy Relapse/Progression (MR)	Malignancy Relapse/Progression (MR) is defined as the time from date of start of study treatment to hematologic malignancy relapse/progression. Calculated for participants with underlying hematologic malignant disease.	From date of start of study treatment to hematologic malignancy relapse/progression, up to approx. 12 months
Secondary	Reduction of daily corticosteroids dose	This includes the assessment of systemic corticosteroid use and daily dose, and the percentage of participants successfully tapered off all systemic corticosteroids until Day 56, by time intervals and overall.	Up to Day 56
Secondary	Cummulative incidence of chronic GvHD	Cumulative incidence of chronic GvHD (cGvHD) includes mild, moderate and severe occurrences.	From Week 1 to long term follow up of month 12