corticosteroid refractory chronic Graft vs Host Disease MedDRA version: 20.1 Level: PT Classification code 10072158 Term: Chronic graft versus host disease in intestine System Organ Class: 10021428 - Immune system disorders MedDRA version: 20.1 Level: PT Classification code 10072159 Term: Chronic graft versus host disease in skin System Organ Class: 10021428 - Immune system disorders MedDRA version: 20.1 Level: PT Classification code 10066261 Term: Chronic graft versus host disease System Org
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Male or female patients =12 years old at the time of signing the ICF ? 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) > 1000/mm3 and platelet count > 25,000/ mm3 ? Patients with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria (Jagasia 2015) prior to randomization: ? 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 ? Patients currently receiving systemic or topical corticosteroids for the treatment of cGvHD for a duration of 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks (or equivalent), OR ? Increase to prednisolone dose to >0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent) ? Patient must accept to be treated with only one of the following BAT options on Cycle 1 Day 1. (Additions and changes are allowed during the course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 132 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 162
Exclusion criteria
Exclusion criteria: ? Patients who have received two or more systemic treatments (BAT) for cGvHD in addition to corticosteroids ± CNI for cGvHD ? Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment ? Patients who were treated with prior JAK inhibitors for aGvHD; except when the patient 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 ? Patients 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. Patients who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible ? Any corticosteroid therapy for indications other than cGvHD at doses >1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of ruxolitinib versus Investigator’s choice Best Available Therapy (BAT) in patients with moderate or severe SR-cGvHD assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 visit.;Secondary Objective: Key Secondary: To compare the rate of failure free survival (FFS) and the change in the modified Lee cGvHD Symptom Scale score between treatment groups Other secondary: ? Best overall response (BOR) ? Estimate ORR at the end of Cycle 3 ? Duration of response ? Overall survival ? Non-relapse mortality (NRM) ? Proportion of patients with =50% reduction in the daily steroid dose at Cycle 7 Day 1 ? Proportion of patients who successfully tapered off all steroids at Cycle 7 Day 1 ? Cumulative incidence of Malignancy Relapse/Recurrence (MR) ? Change in FACT-BMT and EQ-5D ? To assess pharmacokinetics of ruxolitinib ? Safety and tolerability of ruxolitinib and BAT ? Medical resource utilization;Primary end point(s): overall response rate (ORR) on Cycle 7 Day 1 after randomization, defined as the proportion of patients in each arm 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. Scoring of response will be relative to the organ score at randomization.;Timepoint(s) of evaluation of this end point: Cycle 7 Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary: 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 Rate of patients with clinically relevant improvement of the modified Lee symptoms score at Cycle 7 Day 1. FFS will be used as the first key secondary endpoint for all regions except the US (ROW). The modified Lee symptom score will be used as the first key secondary endpoint for the US Other secondary: - Proportion of patients who achieved OR (CR+PR) at any time point (up Cycle 7 day 1 or the start of additional systemic therapy for cGvHD) - To estimate ORR at end of Cycle 3 Proportion of patients who achieved OR (CR+PR) at Cycle 4 Day 1. - Duration of Response Duration of response (DOR) is assessed for responders only - Overall survival, defined as the time from the date of randomization to the date of death due to any cause - Non-relapse mortality (NRM), defined as the time from date of randomization to date of death not preceded by underlying disease relapse/recurrence - Malignancy Relapse/Recurrence (MR) is defined as the time from date of randomization to hematologic malignancy relapse/recurrence - Change in FACT-BMT from baseline to each visit where measured. - Change in EQ-5D from baseline to each visit where measured - Pharmacokinetic parameters of ruxolitinib after a single dose and at steady state. Cmax, AUClast, and AUCinf. Other PK parameters are CL/F, Vz/F, Tmax and T1/2 - Safety and tolerability including myelosuppression, infections, and bleeding will be assessed by monitoring the frequency, duration, and severity of Adverse Events including occurrence of any second primary malignancies, infections, by performing physical exams, and evaluating changes in vital signs from baseline, routine serum chemistry, hematology results and coagulation | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Jordan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactMedical information
Novartis Sverige AB
Outcome results
None listed