Study on the activity, safety, and pharmacokinetics of Ruxolitinib in pediatric patients with moderate to severe chronic graft-versus-host disease following allogeneic stem cell transplantation

ICTRP Studien-ID
NCT03774082 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
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 (BASEC)

Wissenschaftlicher Titel
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 (ICTRP)

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

Untersuchte Krankheit(en)
Graft vs Host Disease (ICTRP)

Untersuchte Intervention
Drug: INC424 (ICTRP)

Studientyp
Interventional (ICTRP)

Studiendesign
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Ein-/Ausschlusskriterien
Gender: All
Maximum age: 17 Years
Minimum age: 28 Days
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 previously 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 (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Overall response rate (ORR) (ICTRP)

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 (ICTRP)

Registrierungsdatum
11.12.2018 (ICTRP)

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Novartis Pharmaceuticals, Novartis Pharmaceuticals (ICTRP)

Sekundäre IDs
2018-003296-35, CINC424G12201 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT03774082 (ICTRP)