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: 20.0Level: PTClassification code 10072158Term: Chronic graft versus host disease in intestineSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.0Level: PTClassification code 10072159Term: Chronic graft versus host disease in skinSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.0Level: PTClassification code 10066261Term: Chronic graft versus host diseaseSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.0Level: 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-IT
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-07-19
• Last Update Posted: 19 February 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• 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 < 6 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
? 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
? Increase to prednisolone dose to >0.25 mg/kg/day after two unsuccessful attempts
to taper the dose
? 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
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 systemic treatment for cGvHD in addition to
corticosteroids ± CNI for cGvHD
? Patients with overlap syndrome defined as presence of simultaneous features of
both chronic and acute GvHD, or patients that transition from 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

Study & Design

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