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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03491215




Registration number
NCT03491215
Ethics application status
Date submitted
20/03/2018
Date registered
9/04/2018

Titles & IDs
Public title
Study of Pharmacokinetics, Activity and Safety of Ruxolitinib in Pediatric Patients With Grade II-IV Acute Graft vs. Host Disease
Scientific title
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
Secondary ID [1] 0 0
2018-000422-55
Secondary ID [2] 0 0
CINC424F12201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Graft Versus Host Disease 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ruxolitinib

Experimental: Ruxolitinib - All pediatric participants received ruxolitinib twice a day (BID) for a planned duration of 24 weeks in either tablet, capsule or oral solution (liquid), depending on the group they were in.


Treatment: Drugs: Ruxolitinib
All enrolled pediatric participants received ruxolitinib as a 5 mg tablet (adult and adolescent formulation) or an oral pediatric formulation (administered as oral solution or capsule dispersed in liquid).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I: Measurement of Pharmacokinetic (PK) Parameter, AUClast, in aGvHD and SR-aGvHD Patients
Timepoint [1] 0 0
Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Primary outcome [2] 0 0
Phase I: Measurement of PK Parameter, Cmax, in aGvHD and SR-aGvHD Patients
Timepoint [2] 0 0
Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Primary outcome [3] 0 0
Phase I: Measurement of PK Parameter, T1/2, in aGvHD and SR-aGvHD Patients
Timepoint [3] 0 0
Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Primary outcome [4] 0 0
Phase I: Measurement of PK Parameter, Ctrough, in aGvHD and SR-aGvHD Patients
Timepoint [4] 0 0
Day 7 at pre-dose
Primary outcome [5] 0 0
Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using AUClast
Timepoint [5] 0 0
Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Primary outcome [6] 0 0
Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using Cmax
Timepoint [6] 0 0
Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Primary outcome [7] 0 0
Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using Ctrough
Timepoint [7] 0 0
Day 7 at pre-dose
Primary outcome [8] 0 0
Phase II: Overall Response Rate (ORR)
Timepoint [8] 0 0
Day 28
Secondary outcome [1] 0 0
Percentage of All Patients Who Achieved a Complete Response (CR) or Partial Response (PR) (Durable Overall Response Rate (ORR))
Timepoint [1] 0 0
Day 56
Secondary outcome [2] 0 0
Percentage of Patients Who Achieved OR (CR+PR) at Day 14
Timepoint [2] 0 0
Day 14
Secondary outcome [3] 0 0
Area Under the Curve (AUClast) Versus Efficacy: Impact of AUClast on Overall Response Rate (ORR) at Day 28
Timepoint [3] 0 0
Day 28
Secondary outcome [4] 0 0
Area Under the Curve (AUClast) Versus Efficacy: Impact of AUClast on Durable Response Rate (DRR) at Day 56
Timepoint [4] 0 0
Day 56
Secondary outcome [5] 0 0
Area Under the Curve (AUClast) Versus Safety: Impact of AUClast on Bleeding
Timepoint [5] 0 0
24 weeks
Secondary outcome [6] 0 0
Area Under the Curve (AUClast) Versus Safety: Impact of AUClast on Infection
Timepoint [6] 0 0
24 weeks
Secondary outcome [7] 0 0
Duration of Response (DOR)
Timepoint [7] 0 0
Months 1, 2 & 6
Secondary outcome [8] 0 0
Weekly Cumulative Steroid Dose for Each Patient up to Day 56
Timepoint [8] 0 0
up to 56 days (Week 1 - Week 8)
Secondary outcome [9] 0 0
Overall Survival (OS) Per Kaplan Meier
Timepoint [9] 0 0
1 Month (M), 2 M, 6M, 12M, 18M
Secondary outcome [10] 0 0
Event-Free Survival (EFS) Per Kaplan-Meier Estimates
Timepoint [10] 0 0
1 Month (M), 2 M, 6M, 12M, 18M
Secondary outcome [11] 0 0
Failure-Free Survival (FFS)
Timepoint [11] 0 0
1 Month (M), 2M, 6M, 12M, 18M, 24M
Secondary outcome [12] 0 0
Non Relapse Mortality (NRM)
Timepoint [12] 0 0
Month (M)1, M2, M6, M12, M18, M24
Secondary outcome [13] 0 0
Incidence of Malignancy Relapse (MR)/Progression
Timepoint [13] 0 0
Month (M) 1, M2, M6, M12, M18, M24,
Secondary outcome [14] 0 0
Cumulative Incidence (CI) of cGvHD
Timepoint [14] 0 0
Month (M) 1, M2, M6, M12, M18, M24
Secondary outcome [15] 0 0
Graft Failure
Timepoint [15] 0 0
2 years
Secondary outcome [16] 0 0
Questionnaire on Acceptability and Palatability
Timepoint [16] 0 0
Day 1, Week 4 (1 month), Week 24 (6 months)
Secondary outcome [17] 0 0
PK Parameter - Maximum Serum Concentration (Cmax) Versus Efficacy
Timepoint [17] 0 0
24 weeks
Secondary outcome [18] 0 0
PK Parameter: Minimum Serum Concentration (Ctrough) Versus Safety
Timepoint [18] 0 0
24 weeks
Secondary outcome [19] 0 0
PK Parameter: Cmax Versus Safety
Timepoint [19] 0 0
24 weeks
Secondary outcome [20] 0 0
PK Parameter: Ctrough Versus Efficacy
Timepoint [20] 0 0
24 weeks
Secondary outcome [21] 0 0
PK Parameter: Profile of Biomarker Concentration Changes Across Different AUC Quantile Groups
Timepoint [21] 0 0
Week 4
Secondary outcome [22] 0 0
PK Parameter: Cmax Versus PD Biomarkers
Timepoint [22] 0 0
24 weeks
Secondary outcome [23] 0 0
PK Parameter: Ctrough Versus PD Biomarkers
Timepoint [23] 0 0
24 weeks
Secondary outcome [24] 0 0
Percentage of Patients Who Achieved Best Overall Response (BOR) up to Day 28
Timepoint [24] 0 0
Up to 28 days and before start of additional aGvHD therapy

Eligibility
Key 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.)
Minimum age
28 Days
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/02/2023
Sample size
Target
Accrual to date
Final
45
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Gent
Country [2] 0 0
Belgium
State/province [2] 0 0
Laeken
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Denmark
State/province [4] 0 0
Copenhagen
Country [5] 0 0
France
State/province [5] 0 0
Lille
Country [6] 0 0
France
State/province [6] 0 0
Nantes Cedex 01
Country [7] 0 0
France
State/province [7] 0 0
Paris 15
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
France
State/province [9] 0 0
Rennes
Country [10] 0 0
France
State/province [10] 0 0
Vandoeuvre Les Nancy
Country [11] 0 0
Italy
State/province [11] 0 0
GE
Country [12] 0 0
Italy
State/province [12] 0 0
RM
Country [13] 0 0
Japan
State/province [13] 0 0
Aichi
Country [14] 0 0
Japan
State/province [14] 0 0
Saitama
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
Spain
State/province [16] 0 0
Catalunya
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03491215