Clinical Trials List
Protocol NumberCINC424C2301
NCT Number(ClinicalTrials.gov Identfier)NCT02913261
2017-01-01 - 2021-11-17
Phase III
Terminated2
ICD-10Z94.9
Transplanted organ and tissue status, unspecified
ICD-9V42.9
Unspecified organ or tissue replaced by transplant
A phase III randomized open-label multi-center study of ruxolitinib versus best available therapy in patients with corticosteroid-refractory acute 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 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- MENG-YAO LU 無
- Chien-Chin Lin 無
- 林建廷 無
- Huai-Hsuan Huang 無
- Wen-Chien Chou 無
- Chieh-Lung Cheng 無
- - - 無
- MING YAO 無
- Tai-Chung Huang 無
- CHENG-HONG TSAI 無
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Corticosteroid Refractory Acute Graft vs Host Disease
Objectives
Primary objective:
to compare the efficacy of ruxolitinib vs. Investigator’s choice Best Available Therapy in patients with Grade II-IV steroid refractory-acute Graft vs. Host Disease assessed by Overall Response Rate (ORR) at Day 28. ORR at Day 28 after randomization is defined as the proportion of patients in each arm demonstrating a complete response or partial response without requirement for additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ stage at the time of randomization.
Test Drug
INC424
Active Ingredient
Ruxolitinib phosphate
Dosage Form
Tablet
Dosage
5 mg
Endpoints
Efficacy assessments
The primary and key secondary endpoints of the trial will be based on:
improvement or resolution of aGvHD manifestations (measures of
body surface area aGvHD skin rash, stool volumes or frequency
per 24h time period, and serum bilirubin levels)
reduction or cessation of required systemic corticosteroids
Safety assessments include:
any progression or recurrence of the underlying hematologic
disease for which the alloSCT has been performed including
malignancy progression or relapse
occurrence of any life-threatening infections,
occurrence of graft failure
occurrence of bleeding
occurrence of any second primary malignancies
Other assessments include:
Incidence of cGvHD
Collection of PK data in order to assess exposure data and
determine how it compares with data from previous studies, and
explore its relationship with efficacy and safety parameters
duration of hospitalization,
To assess exposure-response relationship of ruxolitinib in SRaGvHD
Frequency of hospital readmissions for management of aGvHD,
malignancy relapse, graft failure, and/or infections,
Patient-reported quality of life (QoL)
To Determine mutation and expression status at baseline
To evaluate effect of ruxolitinib on cytokines, aGvHD biomarkers
and immune cell subsets
To explore cytokines and aGvHD biomarkers as
pharmacodynamic markers for ruxolitinib
The primary and key secondary endpoints of the trial will be based on:
improvement or resolution of aGvHD manifestations (measures of
body surface area aGvHD skin rash, stool volumes or frequency
per 24h time period, and serum bilirubin levels)
reduction or cessation of required systemic corticosteroids
Safety assessments include:
any progression or recurrence of the underlying hematologic
disease for which the alloSCT has been performed including
malignancy progression or relapse
occurrence of any life-threatening infections,
occurrence of graft failure
occurrence of bleeding
occurrence of any second primary malignancies
Other assessments include:
Incidence of cGvHD
Collection of PK data in order to assess exposure data and
determine how it compares with data from previous studies, and
explore its relationship with efficacy and safety parameters
duration of hospitalization,
To assess exposure-response relationship of ruxolitinib in SRaGvHD
Frequency of hospital readmissions for management of aGvHD,
malignancy relapse, graft failure, and/or infections,
Patient-reported quality of life (QoL)
To Determine mutation and expression status at baseline
To evaluate effect of ruxolitinib on cytokines, aGvHD biomarkers
and immune cell subsets
To explore cytokines and aGvHD biomarkers as
pharmacodynamic markers for ruxolitinib
Inclution Criteria
1.Male or female patients aged 12 or older
2.Able to swallow tablets
3.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 nonmyeloablative, myeloablative, and reduced intensity conditioning
are eligible
4.Clinically diagnosed Grades II to IV acute GvHD as per standard
criteria occurring after alloSCT requiring systemic immune
suppressive therapy. Biopsy of involved organs with aGvHD is
encouraged but not required for study screening. .Evident myeloid
and platelet engraftment (confirmed within 48h prior to study
treatment start):
absolute neutrophil count (ANC) > 1000/mm3*AND
platelets ≥ 20,000/ mm3
*Use of growth factor supplementation and transfusion support
is allowed.
5.Confirmed diagnosis of steroid refractory aGvHD (confirmed
within 48h prior to study treatment start) defined as patients
administered high-dose systemic corticosteroids
(methylprednisolone 2 mg/kg/day [or equivalent prednisone dose
2.5 mg/kg/day]), given alone or combined with calcineurin
inhibitors (CNI) and either:
A. Progressing based on organ assessment after 5 days compared
to organ stage at the time of initiation of high-dose systemic
steroid +/- CNI for the treatment of Grade II-IV aGvHD,
OR
B. Failure to achieve at a minimum partial response based on
organ assessment after 7 days compared to organ stage at the
time of initiation of high-dose systemic steroid +/- CNI for the
treatment of Grade II-IV aGvHD,
OR
C. Patients who fail corticosteroid taper defined as fulfilling either
one of the following criteria:
1. Requirement for an increase in the corticosteroid dose to
methylprednisolone ≥2 mg/kg/day (or equivalent
prednisone dose ≥2.5 mg/kg/day), OR
2. Failure to taper the methylprednisolone dose to <1
mg/kg/day (or equivalent prednisone dose <1.25
mg/kg/day) for a minimum 7 days
2.Able to swallow tablets
3.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 nonmyeloablative, myeloablative, and reduced intensity conditioning
are eligible
4.Clinically diagnosed Grades II to IV acute GvHD as per standard
criteria occurring after alloSCT requiring systemic immune
suppressive therapy. Biopsy of involved organs with aGvHD is
encouraged but not required for study screening. .Evident myeloid
and platelet engraftment (confirmed within 48h prior to study
treatment start):
absolute neutrophil count (ANC) > 1000/mm3*AND
platelets ≥ 20,000/ mm3
*Use of growth factor supplementation and transfusion support
is allowed.
5.Confirmed diagnosis of steroid refractory aGvHD (confirmed
within 48h prior to study treatment start) defined as patients
administered high-dose systemic corticosteroids
(methylprednisolone 2 mg/kg/day [or equivalent prednisone dose
2.5 mg/kg/day]), given alone or combined with calcineurin
inhibitors (CNI) and either:
A. Progressing based on organ assessment after 5 days compared
to organ stage at the time of initiation of high-dose systemic
steroid +/- CNI for the treatment of Grade II-IV aGvHD,
OR
B. Failure to achieve at a minimum partial response based on
organ assessment after 7 days compared to organ stage at the
time of initiation of high-dose systemic steroid +/- CNI for the
treatment of Grade II-IV aGvHD,
OR
C. Patients who fail corticosteroid taper defined as fulfilling either
one of the following criteria:
1. Requirement for an increase in the corticosteroid dose to
methylprednisolone ≥2 mg/kg/day (or equivalent
prednisone dose ≥2.5 mg/kg/day), OR
2. Failure to taper the methylprednisolone dose to <1
mg/kg/day (or equivalent prednisone dose <1.25
mg/kg/day) for a minimum 7 days
Exclusion Criteria
1.Has received more than one systemic treatment for aGvHD other
than corticosteroids +/- CNI (prophylaxis or treatment).
2.Clinical presentation resembling de novo chronic GvHD or GvHD
overlap syndrome with both acute and chronic GvHD features (as
defined by Jagasia, et al. 2015).
3. Failed prior alloHSCT within the past 6 months.
4. Presence of an active uncontrolled infection including significant
bacterial, fungal, viral or parasitic infection requiring treatment.
Infections are considered controlled if appropriate therapy has been
instituted and, at the time of screening, no signs of progression are
present. Progression of infection is defined as hemodynamic
instability attributable to sepsis, new symptoms, worsening physical
signs or radiographic findings attributable to infection. Persisting
fever without other signs or symptoms will not be interpreted as
progressing infection.
5.Evidence of active viral infection (confirmed by peripheral blood
viral load) including CMV, EBV, HHV-6, HBV, or HCV. Patients
with pre-transplant positive serology results indicative of high risk
for viral reactivation must have negative viral load results within 28
days prior to randomization. Patients whose immune status is
unknown or uncertain (e.g. serologies not obtained prior to
transplant) must have viral load results confirming no evidence of
active viral infection within 28 days prior to randomization.
6. Presence of relapsed primary malignancy, or who have been treated
for relapse after the alloHSCT was performed, or who may require
rapid immune suppression withdrawal as pre-emergent treatment of
early malignancy relapse.
7. Previous participation in a study of any investigational treatment
agent within 30 days of Screening or within 5 half-lives of the study
treatment, whichever is greater
than corticosteroids +/- CNI (prophylaxis or treatment).
2.Clinical presentation resembling de novo chronic GvHD or GvHD
overlap syndrome with both acute and chronic GvHD features (as
defined by Jagasia, et al. 2015).
3. Failed prior alloHSCT within the past 6 months.
4. Presence of an active uncontrolled infection including significant
bacterial, fungal, viral or parasitic infection requiring treatment.
Infections are considered controlled if appropriate therapy has been
instituted and, at the time of screening, no signs of progression are
present. Progression of infection is defined as hemodynamic
instability attributable to sepsis, new symptoms, worsening physical
signs or radiographic findings attributable to infection. Persisting
fever without other signs or symptoms will not be interpreted as
progressing infection.
5.Evidence of active viral infection (confirmed by peripheral blood
viral load) including CMV, EBV, HHV-6, HBV, or HCV. Patients
with pre-transplant positive serology results indicative of high risk
for viral reactivation must have negative viral load results within 28
days prior to randomization. Patients whose immune status is
unknown or uncertain (e.g. serologies not obtained prior to
transplant) must have viral load results confirming no evidence of
active viral infection within 28 days prior to randomization.
6. Presence of relapsed primary malignancy, or who have been treated
for relapse after the alloHSCT was performed, or who may require
rapid immune suppression withdrawal as pre-emergent treatment of
early malignancy relapse.
7. Previous participation in a study of any investigational treatment
agent within 30 days of Screening or within 5 half-lives of the study
treatment, whichever is greater
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
308 participants
