Clinical Trials List
Protocol NumberCINC424G12201
NCT Number(ClinicalTrials.gov Identfier)NCT03774082
2019-12-01 - 2025-12-31
Phase II
Recruiting2
ICD-10D82.2
Immunodeficiency with short-limbed stature
ICD-10D82.3
Immunodeficiency following hereditary defective response to Epstein-Barr virus
ICD-10D82.4
Hyperimmunoglobulin E [IgE] syndrome
ICD-10D82.8
Immunodeficiency associated with other specified major defects
ICD-10D82.9
Immunodeficiency associated with major defect, unspecified
ICD-10D84.0
Lymphocyte function antigen-1 [LFA-1] defect
ICD-10D84.1
Defects in the complement system
ICD-10D89.3
Immune reconstitution syndrome
ICD-10D89.89
Other specified disorders involving the immune mechanism, not elsewhere classified
ICD-10M35.9
Systemic involvement of connective tissue, unspecified
ICD-9279.8
Other specified disorders involving the immune mechanism
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
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- SHIANN-TANG JOU 無
- 周書緯 無
- 張修豪 無
- YUNG-LI YANG 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Graft vs Host Disease
Objectives
Primary objective(s)
To evaluate the activity of ruxolitinib
added to standard dose corticosteroids
+/- CNI in pediatric subjects with
moderate or severe treatment naivecGvHD or SR-cGvHD measured by
overall response rate (ORR) at Cycle 7
Day 1 based on all subjects in the study.
Secondary objective(s)
To assess pharmacokinetics (PK) of
ruxolitinib in treatment-naïve cGvHD
and SR-cGvHD pediatric subjects
To evaluate the safety of ruxolitinib
To assess duration of response (DOR)
To estimate ORR at end of Cycle 3
To assess best overall response (BOR)
To estimate the failure free survival
(FFS)
To assess cumulative incidence of
malignancy relapse/recurrence (MR)
To assess non-relapse mortality (NRM)
To assess overall survival (OS)
To assess a reduction of at least ≥
50% in daily corticosteroid use at Cycle
7 Day 1
To assess a reduction to a low dose
corticosteroid dose at Cycle 7 Day 1
To assess graft failure
Test Drug
INC424
Active Ingredient
Ruxolitinib phosphate
Dosage Form
Tablet/ Oral pediatric formulation
Dosage
5 mg
Endpoints
Primary Outcome Measures :
Overall response rate (ORR) [ Time Frame: Cycle 7 Day 1 (Day 168) ]
ORR is defined as the proportion of subjects demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. The response is assessed per NIH consensus criteria (Lee et al 2015) and scoring of response will be relative to the organ stage at the start of study treatment.
Secondary Outcome Measures :
Ruxolitinib concentrations by timepoint [ Time Frame: Cycle 7 Day 1 (from baseline to Day 168) ]
PK of ruxolitinib in treatment-naïve cGvHD and SR-cGvHD pediatric subjects
Duration of response (DOR) [ Time Frame: From baseline up to end of study treatment, up to 36 months ]
Time from first response until cGvHD progression, death, or the date of addition of systemic therapies for cGvHD
Overall Response Rate (ORR) [ Time Frame: Cycle 4 Day 1 (Day 84) ]
Proportion of subjects who achieve OR (CR+PR)
Best overall response (BOR) [ Time Frame: Until Cycle 7 Day 1 (Day 168) or the start of additional systemic therapy for cGvHD ]
Proportion of subjects who achieved OR (CR+PR) at any time point
Failure free survival (FFS) [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Composite time to event endpoint incorporating the following FFS events: i) relapse or recurrence of underlying disease or death due to underlying disease, ii) non-relapse mortality, or iii) addition or initiation of another systemic therapy for cGvHD
Cumulative incidence of malignancy relapse/recurrence (MR) [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Defined as the time from date of treatment assignment to hematologic malignancy relapse/recurrence. Calculated for subjects with underlying hematologic malignant disease
Non-relapse mortality (NRM) [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Defined as the time from date of treatment assignment to date of death not preceded by underlying disease relapse/recurrence
Overall survival (OS) [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Defined as the time from the date of treatment assignment to the date of death due to any cause
Percentage of participants with ≥50% reduction from baseline in daily corticosteroid dose [ Time Frame: Cycle 7 Day 1 (Day 168) ]
Reduction of at least ≥50% in daily corticosteroid use
Percentage of participants with a reduction to a low dose corticosteriod [ Time Frame: Cycle 7 Day 1 (Day 168) ]
Reduction in daily corticosteroid dose to ≤0.2mg/kg/day methylprednisolone(or equivalent dose of ≤0.25mg/kg/day prednisone or prednisolone)
Graft failure [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Assess using donor cell chimerism, defined as initial whole blood or marrow donor chimerism for those who had ≥ 5% donor cell chimerism at baseline. If donor cell chimerism declines to <5% on subsequent measurements, the graft failure is declared
Overall response rate (ORR) [ Time Frame: Cycle 7 Day 1 (Day 168) ]
ORR is defined as the proportion of subjects demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. The response is assessed per NIH consensus criteria (Lee et al 2015) and scoring of response will be relative to the organ stage at the start of study treatment.
Secondary Outcome Measures :
Ruxolitinib concentrations by timepoint [ Time Frame: Cycle 7 Day 1 (from baseline to Day 168) ]
PK of ruxolitinib in treatment-naïve cGvHD and SR-cGvHD pediatric subjects
Duration of response (DOR) [ Time Frame: From baseline up to end of study treatment, up to 36 months ]
Time from first response until cGvHD progression, death, or the date of addition of systemic therapies for cGvHD
Overall Response Rate (ORR) [ Time Frame: Cycle 4 Day 1 (Day 84) ]
Proportion of subjects who achieve OR (CR+PR)
Best overall response (BOR) [ Time Frame: Until Cycle 7 Day 1 (Day 168) or the start of additional systemic therapy for cGvHD ]
Proportion of subjects who achieved OR (CR+PR) at any time point
Failure free survival (FFS) [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Composite time to event endpoint incorporating the following FFS events: i) relapse or recurrence of underlying disease or death due to underlying disease, ii) non-relapse mortality, or iii) addition or initiation of another systemic therapy for cGvHD
Cumulative incidence of malignancy relapse/recurrence (MR) [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Defined as the time from date of treatment assignment to hematologic malignancy relapse/recurrence. Calculated for subjects with underlying hematologic malignant disease
Non-relapse mortality (NRM) [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Defined as the time from date of treatment assignment to date of death not preceded by underlying disease relapse/recurrence
Overall survival (OS) [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Defined as the time from the date of treatment assignment to the date of death due to any cause
Percentage of participants with ≥50% reduction from baseline in daily corticosteroid dose [ Time Frame: Cycle 7 Day 1 (Day 168) ]
Reduction of at least ≥50% in daily corticosteroid use
Percentage of participants with a reduction to a low dose corticosteriod [ Time Frame: Cycle 7 Day 1 (Day 168) ]
Reduction in daily corticosteroid dose to ≤0.2mg/kg/day methylprednisolone(or equivalent dose of ≤0.25mg/kg/day prednisone or prednisolone)
Graft failure [ Time Frame: From baseline up to 35 days after end of study treatment, up to 37 months ]
Assess using donor cell chimerism, defined as initial whole blood or marrow donor chimerism for those who had ≥ 5% donor cell chimerism at baseline. If donor cell chimerism declines to <5% on subsequent measurements, the graft failure is declared
Inclution 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, 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.
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
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
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
The Estimated Number of Participants
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Taiwan
4 participants
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Global
42 participants
