- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03491215
Study of Pharmacokinetics, Activity and Safety of Ruxolitinib in Pediatric Patients With Grade II-IV Acute Graft vs. Host Disease
A Phase I/II Open-label, Single-arm, Multi-center Study of Ruxolitinib Added to Corticosteroids in Pediatric Patients With Grade II-IV Acute Graft vs. Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Gent, Belgium, 9000
- Novartis Investigative Site
-
Laeken, Belgium, 1020
- Novartis Investigative Site
-
-
-
-
Quebec
-
Montreal, Quebec, Canada, H3T 1C5
- Novartis Investigative Site
-
-
-
-
-
Copenhagen, Denmark, DK-2100
- Novartis Investigative Site
-
-
-
-
-
Lille, France, 59000
- Novartis Investigative Site
-
Nantes Cedex 01, France, 44093
- Novartis Investigative Site
-
Paris Cedex, France, 75019
- Novartis Investigative Site
-
Paris cedex 15, France, 75015
- Novartis Investigative Site
-
Rennes Cedex, France, 35022
- Novartis Investigative Site
-
Vandoeuvre Les Nancy, France, 54511
- Novartis Investigative Site
-
-
-
-
GE
-
Genova, GE, Italy, 16147
- Novartis Investigative Site
-
-
RM
-
Roma, RM, Italy, 00165
- Novartis Investigative Site
-
-
-
-
-
Saitama, Japan, 330 8777
- Novartis Investigative Site
-
-
Aichi
-
Nagoya, Aichi, Japan, 466 8560
- Novartis Investigative Site
-
-
-
-
-
Seoul, Korea, Republic of, 03080
- Novartis Investigative Site
-
-
-
-
-
Barcelona, Spain, 08041
- Novartis Investigative Site
-
Madrid, Spain, 28046
- Novartis Investigative Site
-
Madrid, Spain, 28009
- Novartis Investigative Site
-
-
Catalunya
-
Barcelona, Catalunya, Spain, 08035
- Novartis Investigative Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female patients age ≥28 days and <18 years at the time of informed consent.
- Patients 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.
- Patients with a clinically confirmed diagnosis of grades II-IV aGvHD within 48 hours prior to study treatment start. Patients may have either: Treatment-naïve aGvHD (criteria per Harris et al. 2016) OR Steroid refractory aGvHD as per institutional criteria, or per physician decision in case institutional criteria are not available, and the patient is currently receiving systemic corticosteroids.
- Evident myeloid engraftment with ANC > 1,000/µl and platelet count >20,000/µl. (Use of growth factor supplementation and transfusion support is allowed.)
Exclusion Criteria:
- Has received the following systemic therapy for aGvHD: a) Treatment-naïve aGvHD patients have received any prior systemic treatment of aGvHD except for a maximum 72h of prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of acute GvHD. Patients are allowed to have received prior GvHD prophylaxis which is not counted as systemic treatment (as long as the prophylaxis was started prior to the diagnosis of aGvHD); OR b) SR-aGvHD patients have received two or more prior systemic treatments for aGvHD in addition to corticosteroids
- 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).
- Failed prior alloSCT within the past 6 months.
- Presence of relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed, or who may require rapid immune suppression withdrawal of immune suppression as pre-emergent treatment of early malignancy relapse.
- Acute GvHD occurring after non-scheduled donor leukocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Note: Patients who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
- Any corticosteroid therapy for indications other than aGvHD at doses > 1 mg/kg/day methylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of Screening. Routine corticosteroids administered during conditioning or cell infusion is allowed.
- Patients who received JAK inhibitor therapy for any indication after initiation of current alloSCT conditioning.
Other protocol-defined Inclusion/Exclusion may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ruxolitinib
All patients received ruxolitinib in addition to corticosteroids +/-calcineurin inhibitor (CNI)
|
Ruxolitinib taken orally (5mg tablets) or oral pediatric formulation and dosage based on age group
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Measurement of pharmacokinetic (PK) parameter, AUC, in aGvHD and SR-aGvHD patients
Time Frame: 28 days
|
Phase I: Measurement will be using extensive PK sampling in Groups 1-3 and sparse sampling in Group 4
|
28 days
|
Phase I: Measurement of PK parameter, Cmax, in aGvHD and SR-aGvHD patients
Time Frame: 28 days
|
Phase I: Measurement will be using extensive PK sampling in Groups 1-3 and sparse sampling in Group 4.
|
28 days
|
Phase I: Measurement of PK parameter, T1/2, in aGvHD and SR-aGvHD patients
Time Frame: 28 days
|
Phase I: Measurement will be using extensive PK sampling in Groups 1-3 and sparse sampling in Group 4.
|
28 days
|
Phase I: Measurement of PK parameter, Ctrough, in aGvHD and SR-aGvHD patients
Time Frame: 28 days
|
Phase I: Measurement will use be using extensive PK sampling in Groups 1-3 and sparse sampling in Group 4.
|
28 days
|
Phase I: Age-based determination of recommended phase 2 dose (RP2D) for each of the groups 2-4
Time Frame: 28 days
|
Phase I: Age-based determination of RP2D for was be based on observed PK parameters:
|
28 days
|
Phase II: Overall response rate (ORR)
Time Frame: 28 days
|
Phase II: ORR is defined as the percentage of patients demonstrating a complete response (CR) or partial response (PR) 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 start of the study treatment.
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of patients who achieved OR (CR+PR)
Time Frame: To estimate ORR at Day 14.
|
14 days
|
To estimate ORR at Day 14.
|
PK parameter: Area under the curve (AUC) versus safety
Time Frame: 24 weeks
|
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUC with safety)
|
24 weeks
|
Duration of response (DOR)
Time Frame: 48 weeks
|
DOR is assessed for responders only and is defined as the time from first response until aGvHD progression or the date of additional systemic therapies for aGvHD.
Onset of chronic GvHD, or death without prior observation of aGvHD progression are considered as competing risks.
|
48 weeks
|
Weekly cumulative steroid dose for each patient
Time Frame: up to 56 days
|
To assess the cumulative steroid dose until Day 56
|
up to 56 days
|
Overall Survival (OS)
Time Frame: 2 years
|
OS is defined as the time from the start of treatment to the date of death due to any cause.
|
2 years
|
Event-Free Survival (EFS)
Time Frame: 2 years
|
EFS is defined as the time from start of treatment to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.
|
2 years
|
Failure-Free Survival (FFS)
Time Frame: 2 years
|
FFS is defined as the time from the start of treatment to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment.
|
2 years
|
Non Relapse Mortality (NRM)
Time Frame: 2 years
|
NRM is defined as the time from start of treatment to date of death not preceded by hematologic disease relapse/progression.
|
2 years
|
Incidence of Malignancy Relapse/Progression (MR)
Time Frame: 2 years
|
MR is defined as the time from start of treatment to hematologic malignancy relapse/progression.
Calculated for patients with underlying hematologic malignant disease.
|
2 years
|
Incidence of cGvHD
Time Frame: 2 years
|
cGvHD is defined as the diagnosis of any cGvHD including mild, moderate, severe
|
2 years
|
Monitoring of donor cell chimerism
Time Frame: 2 years
|
Monitoring of donor cell chimerism to assess graft failure is defined as initial whole blood or marrow donor chimerism >5% declining to <5% on subsequent measurements compared to baseline.
|
2 years
|
Questionnaire on acceptability and palatability
Time Frame: 24 weeks
|
Responses from the acceptability and palatability questionnaire for ruxolitinib dose forms used after first dose, 1 month and 6 months.
|
24 weeks
|
PK parameter - maximum serum concentration (Cmax) versus efficacy
Time Frame: 24 weeks
|
To assess pharmacokinetic/pharmacodynamic relationship (comparison of Cmax with efficacy)
|
24 weeks
|
PK parameter: Minimum serum concentration (Ctrough) versus safety
Time Frame: 24 weeks
|
To assess pharmacokinetic/pharmacodynamic relationships (comparison of Ctrough with safety)
|
24 weeks
|
PK parameter: Cmax versus safety
Time Frame: 24 weeks
|
To assess pharmacokinetic/pharmacodynamics relationship (comparison of Cmax with safety)
|
24 weeks
|
PK parameter: Ctrough versus efficacy
Time Frame: 24 weeks
|
To assess pharmacokinetic/pharmacodynamics relationship (comparison of Ctrough with efficacy)
|
24 weeks
|
PK parameter: AUC versus efficacy
Time Frame: 24 weeks
|
To assess pharmacokinetic/pharmacodynamics relationship (comparison of AUC with efficacy)
|
24 weeks
|
PK parameter: AUC versus PD biomarkers
Time Frame: 24 weeks
|
To assess pharmacokinetics/pharmacodynamics relationship (Comparison of AUC with PD biomarkers)
|
24 weeks
|
PK parameter: Cmax versus PD biomarkers
Time Frame: 24 weeks
|
To assess pharmacokinetic/pharmocodynamic relationship (comparison of Cmax with PD biomarkers)
|
24 weeks
|
PK parameter: Ctrough versus PD biomarkers
Time Frame: 24 weeks
|
To assess pharmacokinetic/pharmacodynamics relationship (Ctrough with PD biomarkers)
|
24 weeks
|
Percentage of patients who achieved Overall Response (OR)
Time Frame: Up to 28 days and before start of additional aGvHD therapy
|
Estimation of Best overall response (BOR) - is defined as percentage of patients OR (complete response (CR) + partial response (PR)) at any time and up to Day 28 and before the start of additional systemic aGvHD therapy
|
Up to 28 days and before start of additional aGvHD therapy
|
Percentage of all patients who achieved a complete response (CR) or partial response (PR)
Time Frame: 56 Days
|
To assess the rate of durable ORR at Day 56
|
56 Days
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CINC424F12201
- 2018-000422-55 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Graft Versus Host Disease
-
Mesoblast, Inc.Quintiles, Inc.CompletedGrade B Acute Graft Versus Host Disease | Grade C Acute Graft Versus Host Disease | Grade D Acute Graft Versus Host DiseaseUnited States
-
University of LiegeTerminatedChronic Graft-Versus-Host Disease | Acute Graft-Versus-Host Disease | Steroid Refractory Graft-Versus-Host DiseaseBelgium
-
Jazz PharmaceuticalsCompletedAcute-graft-versus-host Disease | Graft-versus-host DiseaseUnited States, Belgium, United Kingdom, Greece, Germany, Spain, France, Italy, Austria, Canada, Bulgaria, Croatia, Poland, Portugal
-
Jonsson Comprehensive Cancer CenterWithdrawnAcute Graft Versus Host Disease | Gastrointestinal Tract Acute Graft Versus Host Disease | Severe Gastrointestinal Tract Acute Graft Versus Host Disease | Steroid Resistant Gastrointestinal Tract Acute Graft Versus Host DiseaseUnited States
-
AltruBio Inc.CompletedSteroid-refractory Acute Graft-versus-Host Disease | Treatment-refractory Acute Graft-versus-Host DiseaseUnited States
-
Shenzhen Xbiome Biotech Co., Ltd.Beijing Improve-Quality Tech.Co., Ltd.Recruiting
-
Cytopeutics Sdn. Bhd.Universiti Tunku Abdul RahmanActive, not recruitingAcute-graft-versus-host DiseaseMalaysia
-
Incyte CorporationTerminatedAcute Graft-versus-host DiseaseUnited States, Spain, France, Italy, United Kingdom, Germany
-
Incyte CorporationCompletedAcute Graft-versus-host DiseaseJapan
-
Central Hospital, Nancy, FranceUnknown
Clinical Trials on Ruxolitinib
-
First Affiliated Hospital of Zhejiang UniversityXiangya Hospital of Central South University; Second Affiliated Hospital, School... and other collaboratorsRecruitingHematologic Malignancy | Bronchiolitis Obliterans SyndromeChina
-
Novartis PharmaceuticalsTerminatedMyelofibrosis With High Molecular Risk MutationsBelgium, Spain, United Kingdom, Hungary, Italy, Japan, Taiwan, Germany, Canada, Singapore, Austria, Australia, France, Israel, Sweden, Switzerland, Hong Kong, Greece, Turkey, Brazil, Russian Federation, Denmark, Portugal, Norway, Poland
-
Julie NangiaIncyte Corporation; Translational Breast Cancer Research ConsortiumRecruitingDuctal Carcinoma In Situ | Atypical Ductal Hyperplasia | Atypical Lobular Hyperplasia | Lobular Carcinoma In SituUnited States
-
Incyte CorporationRecruiting
-
Beijing Friendship HospitalUnknownHemophagocytic LymphohistiocytosisChina
-
Children's Hospital Medical Center, CincinnatiRecruitingBronchiolitis Obliterans (BO) | Hematopoietic Stem Cell Transplant (HSCT)United States
-
University of JenaCompleted
-
University of Michigan Rogel Cancer CenterCompletedHemophagocytic Syndrome (HPS)United States
-
Margherita MaffioliUnknown
-
University of PittsburghWithdrawnHead and Neck Squamous Cell Carcinoma