Activity, safety and pharmacokinetics in pediatric subjects with moderate and severe chronic graft vs. host disease after allogeneic stem cell transplant

Phase 1

• Conditions: chronic graft versus host disease; MedDRA version: 20.0Level: LLTClassification code 10064677Term: Graft versus host disease in intestineSystem Organ Class: 100000004870; MedDRA version: 20.0Level: LLTClassification code 10075161Term: Graft versus host disease in GI tractSystem Organ Class: 100000004870; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003296-35-LT
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-10
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 42

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, haploidentical) 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:
o 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.

Additional inclusion criteria as per fulll protocol may apply.
Are the trial subjects under 18? yes
Number of subjects for this age range: 42
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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/day methylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of the screening visit.
• History of progressive multifocal leukoencephalopathy (PML).
• Presence of severely impaired renal function

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

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