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

A Phase II Open-label, Single-arm, Multi-center Study of Ruxolitinib Added to Corticosteroids in Pediatric Subjects With Moderate and Severe Chronic Graft vs. Host Disease After Allogeneic Stem Cell Transplantation

ClinicalTrials.gov Identifier: NCT03774082

Novartis Reference Number: CINC424G12201

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
Graft vs Host Disease
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
42 participants
Start date 
May 20, 2020
Completion date 
Aug 24, 2026
Gender 
All
Age(s)
18 Years and older (Child, Adult)

Interventions

Drug
INC424
Ruxolitinib is taken orally either as 5mg tablets or as pediatric formulation (dosage based on age group)

Eligibility Criteria

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, 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

Study Locations

Brazil
Novartis Investigative Site
Recruiting
Sao Paulo, 04039 001
-
Brazil
Czechia
Novartis Investigative Site
Recruiting
Praha 5, 150 06
-
Czechia
India
Novartis Investigative Site
Recruiting
Tamil Nadu, 600035
Chennai
India
Novartis Investigative Site
Recruiting
Bangalore, 560099
Karnataka
India
Novartis Investigative Site
Recruiting
Pune, 411004
Maharashtra
India
Italy
Novartis Investigative Site
Recruiting
Roma, 00165
ITA
Italy
Japan
Novartis Investigative Site
Recruiting
Nagoya, 466 8560
Aichi
Japan
Novartis Investigative Site
Recruiting
Saitama, 330 8777
-
Japan
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 05505
-
Korea, Republic of
Lithuania
Novartis Investigative Site
Recruiting
Vinius, 08406
-
Lithuania
Russian Federation
Novartis Investigative Site
Recruiting
Moscow, 117997
-
Russian Federation
Novartis Investigative Site
Recruiting
Sain Petersburg, 197022
-
Russian Federation
Slovakia
Novartis Investigative Site
Recruiting
Bratislava, 833 40
-
Slovakia
Spain
Novartis Investigative Site
Recruiting
Malaga, 29010
Andalucia
Spain
Novartis Investigative Site
Recruiting
Salamanca, 37007
Castilla Y Leon
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Valencia, 46026
Comunidad Valenciana
Spain
Novartis Investigative Site
Recruiting
Madrid, 28009
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28046
-
Spain
Switzerland
Novartis Investigative Site
Recruiting
Zuerich, 8032
-
Switzerland
Taiwan
Novartis Investigative Site
Recruiting
Taichung, 40447
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10002
-
Taiwan
Thailand
Novartis Investigative Site
Recruiting
Bangkok noi, 10700
Bangkok
Thailand
Novartis Investigative Site
Recruiting
Bangkok, 10330
-
Thailand
Turkey
Novartis Investigative Site
Recruiting
Adana,
-
Turkey
Novartis Investigative Site
Recruiting
Antalya, 07070
-
Turkey

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Name: 
Novartis Pharmaceuticals
Phone: 
+81337978748
Email: 

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Call 1-999-669-6682 or email [email protected]