Activity Safety and Pharmacokinetics in Pediatric Subjects With Moderate and Severe Chronic Graft vs. Host Disease After Allogeneic Stem Cell Transplant

  • STATUS
    Recruiting
  • End date
    Feb 14, 2025
  • participants needed
    42
  • sponsor
    Novartis Pharmaceuticals
Updated on 17 October 2021
cancer
corticosteroids
ruxolitinib
immunosuppressive agents
myeloablative conditioning
chronic graft versus host disease

Summary

This open-label, single-arm, Phase II multi-center study will enroll approximately 42 subjects and investigate the activity, pharmacokinetics and safety of ruxolitinib added to the subject's immunosuppressive regimen among infants, children, and adolescents aged 28 days to <18 years old with either moderate to severe treatment-naive cGvHD or SR-cGvHD. Subjects will be grouped according to their age as follows: Group 1 includes subjects 12y to <18y, Group 2 includes subjects 6y to <12y, Group 3 includes subjects 2y to <6y, and Group 4 includes subjects 28days to <2y.

Details
Condition Graft-Versus-Host Disease, Graft-Versus-Host Disease (GVHD), graft versus host disease, graft-versus-host-disease
Treatment INC424
Clinical Study IdentifierNCT03774082
SponsorNovartis Pharmaceuticals
Last Modified on17 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or female subjects age 28 days and <18 years at the time of informed consent
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 o Steroid-refractory moderate to severe cGvHD as per institutional
criteria, or per physician decision in case institutional criteria are not
available, and still receiving systemic corticosteroids for the treatment of
cGvHD for a duration of <18 months prior to Cycle 1 Day 1. In case the
corticosteroids were interrupted due to response, the duration of < 18 months
applies to the last period of corticosteroid use

Exclusion Criteria

SR-cGvHD subjects with a prior cGvHD treatment with a JAK1- or a JAK2- or a JAK1/2-inhibitor, except when the subject achieved complete or partial response and has been off JAK inhibitor treatment for at least 4 weeks prior to Cycle Day 1 or up to 5 times the half-life of the prior JAK inhibitor, whichever is longer
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)
Any corticosteroid therapy for indications other than cGvHD at doses > 1 mg/kg/daymethylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of the screening visit
History of progressive multifocal leuko-encephalopathy (PML)
Presence of severely impaired renal function
Other protocol-defined inclusion/exclusion criteria may apply
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