A phase 2 trial of Ruxolotinib in pediatric patients with moderate and severe chronic graft vs host disease
- Conditions
- Health Condition 1: D758- Other specified diseases of bloodand blood-forming organs
- Registration Number
- CTRI/2019/11/021974
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
Subjects who 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 myeloablative or reduced intensity conditioning are eligible.
Subjects with diagnosed moderate to severe cGvHD according to NIH 2014 Consensus Criteria (Section 16.2) prior to Cycle 1 Day 1. Other possible diagnoses for clinical symptoms supporting cGvHD diagnoses must be excluded (e.g., infection, drug side effects, malignancy). Subjects must be either:
Treatment-naive cGvHD subjects that have not received any prior systemic treatment for cGvHD except for a maximum 72h of prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of chronic GvHD. Subjects are allowed to have received prior systemic treatment for cGvHD prophylaxis (as long as the prophylaxis was started prior to the diagnosis of cGvHD).
OR Steroid-refractory moderate to severe cGvHD as per institutional criteria, and still receiving systemic corticosteroids for the treatment of cGvHD for a duration of <18 months prior to Cycle 1 Day 1.
Subjects who initiated systemic calcineurin inhibitors (CNI; cyclosporine or tacrolimus) within 3 weeks prior to start of ruxolitinib on Cycle 1 Day 1. Note: systemic CNI are allowed when initiated > 3 weeks from start of ruxolitinib.
Failed prior alloSCT within the past 6 months
Significant respiratory disease including subjects who are on mechanical ventilation or who have a resting oxygen saturation < 90% by pulse-oximetry on room-air.
Impairment of gastrointestinal (GI) function (unrelated to GvHD) or GI disease (unrelated to GvHD) that may significantly alter the absorption of oral ruxolitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection),
Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to cGvHD and ongoing organ dysfunction)
Presence of clinically active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
Known human immunodeficiency virus (HIV) infection.
Evidence of uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) based on assessment done by Investigator or delegate.
Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
History of bone disorders such as osteogenesis imperfecta, rickets, renal osteodystrophy, osteomyelitis, osteopenia, fibrous dysplasia, osteomalacia etc. prior to the underlying diagnosis which resulted in the alloSCT.
History of endocrine or kidney related growth retardation prior to the underlying diagnosis which resulted in the alloSCT.
Evidence of clinically active tuberculosis (clinical diagnosis per local practice)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall response rate (ORR)Timepoint: Proportion of subjects who achieve OR at Cycle 4 Day 1
- Secondary Outcome Measures
Name Time Method Ruxolitinib concentrations by timepoint <br/ ><br>Duration of response (DOR) <br/ ><br>Overall Response Rate (ORR) <br/ ><br>Best overall response (BOR) <br/ ><br>Cumulative incidence of malignancy relapse/recurrence (MR) <br/ ><br>Non-relapse mortality (NRM)Timepoint: Cycle 7 Day 1 (from baseline to Day 168) <br/ ><br> From baseline up to end of study treatment, up to 36 months <br/ ><br>Cycle 4 Day 1 (Day 84) <br/ ><br>Until Cycle 7 Day 1 (Day 168) or the start of additional systemic therapy for cGvHD <br/ ><br>From baseline up to 35 days after end of study treatment, up to 37 months <br/ ><br>From baseline up to 35 days after end of study treatment, up to 37 months <br/ ><br> <br/ ><br>