Safety and efficacy of ruxolitinib versus best available therapy in patients with corticosteroid-refractory acute graft vs. host disease after allogeneic stem cell transplantatio

Phase 1

• Conditions: corticosteroid-refractory acute graft vs. host disease after allogeneic stem cell transplantation; MedDRA version: 20.1Level: PTClassification code 10066260Term: Acute graft versus host diseaseSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.1Level: PTClassification code 10066262Term: Acute graft versus host disease in skinSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.1Level: PTClassification code 10066264Term: Acute graft versus host disease in intestineSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.1Level: PTClassification code 10066263Term: Acute graft versus host disease in liverSystem Organ Class: 10021428 - Immune system disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002584-33-CZ
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-21
• Last Update Posted: 17 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 308

Inclusion Criteria

- 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
- Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive
therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
- Confirmed diagnosis of corticosteroid refractory aGvHD defined as:
• Patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:
• Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,
OR
• 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 high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,
OR
• Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria:
• Requirement for an increase in the corticosteroid dose to methylprednisolone =2 mg/kg/day (or equivalent prednisone dose =2.5 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 7 days.
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 281
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion Criteria

- Has received more than one systemic treatment for steriod refractory aGvHD,
- Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features (as defined by Jagasia, et al. 2015)
- Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection.
Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Evidence of uncontrolled viral infection including CMV, EBV, HHV-6, HBV, or HCV based on assessment by the treating physicial.
- Presence of relapsed primary malignancy, or who have been treated for relapse after the alloHSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

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