Activity, Safety and Pharmacokinetics in Pediatric Subjects With Moderate and Severe Chronic Graft vs. Host Disease After Allogeneic Stem Cell Transplant
- Conditions
- Graft vs Host Disease
- Registration Number
- NCT03774082
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> - Male or female subjects age =28 days and <18 years at the time of informed consent.<br><br> - Subjects who have undergone alloSCT from any donor source (matched unrelated donor,<br> sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord<br> blood. Recipients of myeloablative or reduced intensity conditioning are eligible.<br><br> - Subjects with diagnosed moderate to severe cGvHD according to NIH 2014 Consensus<br> Criteria (Section 16.2) prior to Cycle 1 Day 1. Other possible diagnoses for<br> clinical symptoms supporting cGvHD diagnoses must be excluded (e.g., infection, drug<br> side effects, malignancy). Subjects must be either:<br><br> - Treatment-naive cGvHD subjects that have not received any prior systemic<br> treatment for cGvHD except for a maximum 72h of prior systemic corticosteroid<br> therapy of methylprednisolone or equivalent after the onset of chronic GvHD.<br> Subjects are allowed to have received prior systemic treatment for cGvHD<br> prophylaxis (as long as the prophylaxis was started prior to the diagnosis of<br> cGvHD).<br><br>OR o Steroid-refractory moderate to severe cGvHD as per institutional criteria, or per<br>physician decision in case institutional criteria are not available, and still receiving<br>systemic corticosteroids for the treatment of cGvHD for a duration of <18 months prior to<br>Cycle 1 Day 1. In case the corticosteroids were previously interrupted due to response,<br>the duration of < 18 months applies to the last period of corticosteroid use.<br><br>Exclusion Criteria:<br><br> - SR-cGvHD subjects with a prior cGvHD treatment with a JAK1- or a JAK2- or a<br> JAK1/2-inhibitor, except when the subject achieved complete or partial response and<br> has been off JAK inhibitor treatment for at least 4 weeks prior to Cycle Day 1 or up<br> to 5 times the half-life of the prior JAK inhibitor, whichever is longer.<br><br> * Subjects who initiated systemic calcineurin inhibitors (CNI; cyclosporine or<br> tacrolimus) within 3 weeks prior to start of ruxolitinib on Cycle 1 Day 1. Note:<br> systemic CNI are allowed when initiated > 3 weeks from start of ruxolitinib.<br><br> - Failed prior alloSCT within the past 6 months<br><br> - Significant respiratory disease including subjects who are on mechanical ventilation<br> or who have a resting oxygen saturation < 90% by pulse-oximetry on room-air.<br><br> - Impairment of gastrointestinal (GI) function (unrelated to GvHD) or GI disease<br> (unrelated to GvHD) that may significantly alter the absorption of oral ruxolitinib<br> (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption<br> syndrome or small bowel resection),<br><br> - Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive<br> disease of the liver (defined as persistent bilirubin abnormalities not attributable<br> to cGvHD and ongoing organ dysfunction)<br><br> - Presence of clinically active uncontrolled infection including significant<br> bacterial, fungal, viral or parasitic infection requiring treatment.<br><br> - Known human immunodeficiency virus (HIV) infection.<br><br> - Evidence of uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) based on<br> assessment done by Investigator or delegate.<br><br> - Known allergies, hypersensitivity, or intolerance to any of the study medications,<br> excipients, or similar compounds.<br><br> - History of bone disorders such as osteogenesis imperfecta, rickets, renal<br> osteodystrophy, osteomyelitis, osteopenia, fibrous dysplasia, osteomalacia etc.<br> prior to the underlying diagnosis which resulted in the alloSCT.<br><br> - History of endocrine or kidney related growth retardation prior to the underlying<br> diagnosis which resulted in the alloSCT.<br><br> - Evidence of clinically active tuberculosis (clinical diagnosis per local practice)<br><br> - Any corticosteroid therapy for indications other than cGvHD at doses > 1<br> mg/kg/daymethylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7<br> days of the screening visit.<br><br> - History of progressive multifocal leuko-encephalopathy (PML).<br><br> - Presence of severely impaired renal function<br><br>Other protocol-defined inclusion/exclusion criteria may apply
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall response rate (ORR)
- Secondary Outcome Measures
Name Time Method Ruxolitinib concentrations by timepoint;Duration of response (DOR);Overall Response Rate (ORR);Best overall response (BOR);Failure free survival (FFS);Cumulative incidence of malignancy relapse/recurrence (MR);Non-relapse mortality (NRM);Overall survival (OS);Percentage of participants with =50% reduction from baseline in daily corticosteroid dose;Percentage of participants with a reduction to a low dose corticosteriod;Graft failure