Study of efficacy and safety of ruxolitinib vs. best available therapy (BAT) in patients with corticosteroid refractory chronic graft versus host disease after bone marrow transplantatio

Phase 1

• Conditions: corticosteroid refractory chronic Graft vs Host Disease; MedDRA version: 20.1Level: PTClassification code 10072158Term: Chronic graft versus host disease in intestineSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.1Level: PTClassification code 10072159Term: Chronic graft versus host disease in skinSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.1Level: PTClassification code 10066261Term: Chronic graft versus host diseaseSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.1Level: PTClassification code 10072160Term: Chronic graft versus host disease in liverSystem Organ Class: 10021428 - Immune system disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004432-38-BG
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-11-06
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 324

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 < 12 months prior to Cycle 1 Day 1 (if applicable), and have a confirmed diagnosis of steroid refractory cGvHD defined per 2014 NIH consensus criteria (Martin 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)
? 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

? 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 1 Day 1

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified