Steroid-refractory Acute Graft Versus Host Disease
Conditions
Keywords
SR-aGvHD, aGvHD, acute graft-versus-host disease, ruxolitinib, Chinese patients, corticosteroid-refractory, Grade II-IV, Grade II to IV
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.
Interventions
DRUGRuxolitinib
Ruxolitinib is taken orally daily at 10 mg BID, given as two 5-mg tablets.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 100 Years
Healthy volunteers
No
Inclusion 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 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: 1. 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 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 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 ≥ 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. 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 /
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) at Day 28 per Investigators | Day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Durable Overall response rate (ORR) at Day 56 | 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. |
| Duration of Response (DOR) | From Week 1 to long term follow up Month 12 | DOR is defined as the time from first response until aGvHD progression or the date of additional systemic therapies for aGvHD. |
| Best overall response (BOR) | From week 1 to Day 28 | 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. |
| Overall survival (OS) | From the date of start of study treatment to date of death, up to approx. 12 months | Overall survival (OS) is defined as the time from the date of start of study treatment to date of death due to any cause. |
| Non-relapse mortality (NRM) | From date of start of study treatment to date of death, up to approx. 12 months | 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. |
| Event-free survival (EFS) | 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 | 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. |
| Failure-free survival (FFS) | 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 | 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. |
| Malignancy Relapse/Progression (MR) | From date of start of study treatment to hematologic malignancy relapse/progression, up to approx. 12 months | 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. |
| Reduction of daily corticosteroids dose | Up to Day 56 | 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. |
| Cumulative incidence of chronic GvHD | From Week 1 to long term follow up of month 12 | Cumulative incidence of chronic GvHD (cGvHD) includes mild, moderate and severe occurrences. |
Countries
China
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed