Overview

Safety and Efficacy of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation

Status:
Completed
Trial end date:
2021-04-23
Target enrollment:
0
Participant gender:
All
Summary
To evaluate the safety and efficacy of ruxolitinib compared to Best Available Therapy in patients with corticosteroid-refractory acute graft vs. host disease after allogeneic stem cell transplantation
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Novartis Pharmaceuticals
Criteria
Inclusion Criteria:

- Have undergone Allogeneic Stem Cell Transplanttaion (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 steroid 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.

Exclusion Criteria:

- Has received more than one systemic treatment for steroid refractory aGvHD.

- 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 Cytomegalovirus (CMV), Epstein-Barr
Virus (EBV), Human Herpes Virus-6 (HHV-6), Hepatitis Virus (HBV), or Hepatitis C Virus
(HCV) based on assessment by the treating physician.

- 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.