chronic graft versus host disease MedDRA version: 20.0 Level: LLT Classification code 10064677 Term: Graft versus host disease in intestine System Organ Class: 100000004870 MedDRA version: 20.0 Level: LLT Classification code 10075161 Term: Graft versus host disease in GI tract System Organ Class: 100000004870
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female subjects age =28 days and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • SR-cGvHD subjects with a prior cGvHD treatment with a JAK1- or a JAK2- or a JAK1/2-inhibitor, except when the subject achieved complete or partial response and has been off JAK inhibitor treatment for at least 4 weeks prior to Cycle Day 1 or up to 5 times the half-life of the prior JAK inhibitor, whichever is longer. * Subjects who initiated systemic calcineurin inhibitors (CNI; cyclosporine or tacrolimus) within 3 weeks prior to start of ruxolitinib on Cycle 1 Day 1. Note: systemic CNI are allowed when initiated > 3 weeks from start of ruxolitinib. • Failed prior alloSCT within the past 6 months • Significant respiratory disease including subjects who are on mechanical ventilation or who have a resting oxygen saturation 1 mg/kg/day methylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of the screening visit. • History of progressive multifocal leukoencephalopathy (PML). • Presence of severely impaired renal function Other protocol-defined inclusion/exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the activity of ruxolitinib added to standard dose corticosteroids +/- CNI in pediatric subjects with moderate or severe treatment naivecGvHD or SR-cGvHD measured by overall response rate (ORR) at Cycle 7 Day 1 based on all subjects in the study;Secondary Objective: - To assess pharmacokinetics (PK) of ruxolitinib in treatment-naïve cGvHD and SR-cGvHD pediatric subjects - To evaluate the safety of ruxolitinib ? ? - To assess duration of response (DOR) - To estimate ORR at end of Cycle 3 - To assess best overall response (BOR) - To estimate the failure free survival (FFS) - To assess cumulative incidence of malignancy relapse/recurrence (MR) - To assess non-relapse mortality (NRM) - To assess overall survival (OS) - To assess a reduction of at least = 50% in daily corticosteroid use at Cycle 7 Day 1 - To assess a reduction to a low dose corticosteroid dose at Cycle 7 Day 1 - To assess graft failure;Primary end point(s): Overall Response Rate ORR defined as the proportion of subjects demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response;Timepoint(s) of evaluation of this end point: Cycle 7 Day 1 (Day 168) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Ruxolitinib concentrations by timepoint 2. Duration of response (DOR) assessed for responders only. DOR is defined as the time from first response until cGvHD progression, death, or the date of addition of systemic therapies for cGvHD 3. Proportion of subjects who achieve OR (CR+PR) at Cycle 4 Day 1 4. Proportion of subjects who achieved OR (CR+PR) at any time point 5. Composite time to event endpoint incorporating the following FFS events: i) relapse or recurrence of underlying disease or death due to underlying disease, ii) non-relapse mortality, or iii) addition or initiation of another systemic therapy for cGvHD 6. Malignancy relapse/recurrence (MR) is defined as the time from date of treatment assignment to hematologic malignancy relapse/recurrence. Calculated for subjects with underlying hematologic malignant disease 7. Non-relapse mortality (NRM), defined as the time from date of treatment assignment to date of death not preceded by underlying disease relapse/recurrence. 8. Overall survival, defined as the time from the date of treatment assignment to the date of death due to any cause 9. Proportion of subjects with = 50% reduction from baseline in daily corticosteroid dose at Cycle 7 Day 1 10. Proportion of subjects with reduction from baseline in daily corticosteroid dose to = 0.2 mg/kg/day methylprednisolone (or equivalent dose of = 0.25 mg/kg/day prednisone or prednisolone) at Cycle 7 Day 1 11. Proportion of subjects with reduction from baseline in daily corticosteroid dose to = 0.2 mg/kg/day methylprednisolone (or equivalent dose of = 0.25 mg/kg/day prednisone or prednisolone) at Cycle 7 Day 1;Timepoint(s) of evaluation of this end point: 1. Cycle 7 Day 1 (from baseline to Day 168) 2. From baseline up to endof study treatment, up to 36 months 3. Cycle 4 Day 1 (Day 84) 4. Until Cycle 7 Day 1 (Day 168) or the start of additional systemic therapy for cGvHD 5. From baseline up to 35 days after end of study treatment, up to 37 mont | — |
Countries
Argentina, Brazil, Canada, Chile, Czechia, Czech Republic, Germany, Greece, India, Italy, Japan, Korea, Republic of, Lithuania, Russian Federation, Saudi Arabia, Slovakia, Slovenia, Spain, Switzerland, Taiwan, Thailand, Turkey
Contacts
Public ContactDRA information desk
Novartis Slovakia s.r.o.
Outcome results
None listed