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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02913261




Registration number
NCT02913261
Ethics application status
Date submitted
18/09/2016
Date registered
23/09/2016
Date last updated
8/02/2023

Titles & IDs
Public title
Safety and Efficacy of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation
Scientific title
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
Secondary ID [1] 0 0
2016-002584-33
Secondary ID [2] 0 0
CINC424C2301
Universal Trial Number (UTN)
Trial acronym
REACH2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Corticosteroid Refractory Acute Graft vs 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 (RUX)
Treatment: Drugs - Best Available Therapy (BAT)

Experimental: Ruxolitinib - These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.

Active Comparator: Best Available Therapy (BAT) - These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.


Treatment: Drugs: Ruxolitinib (RUX)
Ruxolitinib was provided as 5 mg tablets for oral use.

Treatment: Drugs: Best Available Therapy (BAT)
BAT was based on the investigator's best judgment, taking into account the manufacturer's instructions, labeling, patient's medical condition, and institutional guidelines for any dose adjustment. The BAT in this study was identified by the investigator prior to patient randomization among the following treatments currently used in this setting: anti-thymocyte globulin (ATG), extracorporeal photopheresis (ECP), mesenchymal stromal cells (MSC), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), etanercept, or infliximab. No other types or combinations of BAT were permitted.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) at Day 28
Timepoint [1] 0 0
Day 28
Secondary outcome [1] 0 0
Durable Overall Response Rate (DORR) (Key Secondary Endpoint) at Day 56
Timepoint [1] 0 0
Day 56
Secondary outcome [2] 0 0
Overall Response Rate (ORR) at Day 14
Timepoint [2] 0 0
Day 14
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Cumulative Steroid Dosing Until Day 56
Timepoint [4] 0 0
up to Day 56
Secondary outcome [5] 0 0
Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval
Timepoint [5] 0 0
1, 2, 6, 12, 18 & 24 months
Secondary outcome [6] 0 0
Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval
Timepoint [6] 0 0
1, 2, 6, 12, 18 & 24 months
Secondary outcome [7] 0 0
Cumulative Incidence Rate of Failure-Free Survival (FFS)
Timepoint [7] 0 0
1, 2, 6, 12, 18, & 24 Months
Secondary outcome [8] 0 0
Cumulative Probability of Non Relapse Mortality (NRM)
Timepoint [8] 0 0
1, 2, 6, 12, 18 & 24 months
Secondary outcome [9] 0 0
Cumulative Probability of Malignancy Relapse/Progression (MR)
Timepoint [9] 0 0
1, 2, 6, 12 , 18 & 24 months
Secondary outcome [10] 0 0
Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD)
Timepoint [10] 0 0
1, 2, 6, 12, 18 & 24 months
Secondary outcome [11] 0 0
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Response Rate
Timepoint [11] 0 0
Day 28
Secondary outcome [12] 0 0
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK- Durable Overall Response Rate (DORR)
Timepoint [12] 0 0
Day 56
Secondary outcome [13] 0 0
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Survival
Timepoint [13] 0 0
up to 24 months
Secondary outcome [14] 0 0
Best Overall Response Rate (BOR)
Timepoint [14] 0 0
up to Day 28
Secondary outcome [15] 0 0
Patient Reported Outcomes (PROs): Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Total Score
Timepoint [15] 0 0
Baseline, Week 24
Secondary outcome [16] 0 0
Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score
Timepoint [16] 0 0
Baseline, Week 24
Secondary outcome [17] 0 0
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib
Timepoint [17] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose
Secondary outcome [18] 0 0
Pharmacokinetic (PK) Parameter: Plasma Concentration at Peak (Cmax) of Ruxolitinib
Timepoint [18] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose
Secondary outcome [19] 0 0
Pharmacokinetic (PK) Parameter: CL/F of Ruxolitinib
Timepoint [19] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose
Secondary outcome [20] 0 0
Pharmacokinetic (PK) Parameter: VzF of Ruxolitinib
Timepoint [20] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose
Secondary outcome [21] 0 0
Pharmacokinetic (PK) Parameter: Lambda_z of Ruxolitinib
Timepoint [21] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose
Secondary outcome [22] 0 0
Pharmacokinetic (PK) Parameter: T1/2 of Ruxolitinib
Timepoint [22] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose
Secondary outcome [23] 0 0
Pharmacokinetic (PK) Parameter: Tmax of Ruxolitinib
Timepoint [23] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose
Secondary outcome [24] 0 0
Pharmacokinetic (PK) Parameter: Racc of Ruxolitinib
Timepoint [24] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose
Secondary outcome [25] 0 0
Pharmacokinetic (PK) Parameter: Ctrough of Ruxolitinib
Timepoint [25] 0 0
pre-dose

Eligibility
Key inclusion criteria
- Have undergone Allogeneic Stem Cell Transplanttaion (alloSCT) from any donor source
(matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral
blood stem cells, or cord blood. Recipients of non- myeloablative, myeloablative, and
reduced intensity conditioning are eligible

- 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.

- Confirmed diagnosis of steroid refractory aGvHD 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:

- Progressing based on organ assessment after at least 3 days compared to organ
stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for
the treatment of Grade II-IV aGvHD, OR

- 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
corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,OR

- Patients who fail corticosteroid taper defined as fulfilling either one of the
following criteria:

- Requirement for an increase in the corticosteroid dose to methylprednisolone =2
mg/kg/day (or equivalent prednisone dose =2.5 mg/kg/day) , OR

- Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent
prednisone dose <0.6 mg/kg/day) for a minimum 7 days.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has received more than one systemic treatment for steroid refractory aGvHD.

- 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.

- Evidence of uncontrolled viral infection including Cytomegalovirus (CMV), Epstein-Barr
Virus (EBV), Human Herpes Virus-6 (HHV-6), Hepatitis Virus (HBV), or Hepatitis C Virus
(HCV) based on assessment by the treating physician.

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 3
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [3] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [4] 0 0
Novartis Investigative Site - Murdoch
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3002 - Parkville
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Linz
Country [3] 0 0
Bulgaria
State/province [3] 0 0
Sofia
Country [4] 0 0
Canada
State/province [4] 0 0
Alberta
Country [5] 0 0
Canada
State/province [5] 0 0
British Columbia
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Canada
State/province [8] 0 0
Saskatchewan
Country [9] 0 0
Czechia
State/province [9] 0 0
Czech Republic
Country [10] 0 0
Denmark
State/province [10] 0 0
Copenhagen
Country [11] 0 0
France
State/province [11] 0 0
Loire
Country [12] 0 0
France
State/province [12] 0 0
Angers Cedex 1
Country [13] 0 0
France
State/province [13] 0 0
Besancon cedex
Country [14] 0 0
France
State/province [14] 0 0
Grenoble
Country [15] 0 0
France
State/province [15] 0 0
Lille
Country [16] 0 0
France
State/province [16] 0 0
Limoges cedex
Country [17] 0 0
France
State/province [17] 0 0
Nice Cedex
Country [18] 0 0
France
State/province [18] 0 0
Paris Cedex 10
Country [19] 0 0
France
State/province [19] 0 0
Paris Cedex
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
France
State/province [21] 0 0
Pessac
Country [22] 0 0
France
State/province [22] 0 0
Pierre Benite Cedex
Country [23] 0 0
France
State/province [23] 0 0
Toulouse
Country [24] 0 0
France
State/province [24] 0 0
Vandoeuvre les Nancy cedex
Country [25] 0 0
Germany
State/province [25] 0 0
Baden-Wuerttemberg
Country [26] 0 0
Germany
State/province [26] 0 0
Augsburg
Country [27] 0 0
Germany
State/province [27] 0 0
Berlin
Country [28] 0 0
Germany
State/province [28] 0 0
Dresden
Country [29] 0 0
Germany
State/province [29] 0 0
Duesseldorf
Country [30] 0 0
Germany
State/province [30] 0 0
Essen
Country [31] 0 0
Germany
State/province [31] 0 0
Freiburg
Country [32] 0 0
Germany
State/province [32] 0 0
Hamburg
Country [33] 0 0
Germany
State/province [33] 0 0
Hannover
Country [34] 0 0
Germany
State/province [34] 0 0
Jena
Country [35] 0 0
Germany
State/province [35] 0 0
Leipzig
Country [36] 0 0
Germany
State/province [36] 0 0
Mainz
Country [37] 0 0
Germany
State/province [37] 0 0
Muenster
Country [38] 0 0
Germany
State/province [38] 0 0
Tübingen
Country [39] 0 0
Germany
State/province [39] 0 0
Ulm
Country [40] 0 0
Greece
State/province [40] 0 0
GR
Country [41] 0 0
Hong Kong
State/province [41] 0 0
Hong Kong
Country [42] 0 0
Israel
State/province [42] 0 0
Haifa
Country [43] 0 0
Israel
State/province [43] 0 0
Jerusalem
Country [44] 0 0
Israel
State/province [44] 0 0
Petach Tikva
Country [45] 0 0
Israel
State/province [45] 0 0
Tel Aviv
Country [46] 0 0
Italy
State/province [46] 0 0
AN
Country [47] 0 0
Italy
State/province [47] 0 0
BG
Country [48] 0 0
Italy
State/province [48] 0 0
BO
Country [49] 0 0
Italy
State/province [49] 0 0
BS
Country [50] 0 0
Italy
State/province [50] 0 0
FG
Country [51] 0 0
Italy
State/province [51] 0 0
FI
Country [52] 0 0
Italy
State/province [52] 0 0
GE
Country [53] 0 0
Italy
State/province [53] 0 0
MI
Country [54] 0 0
Italy
State/province [54] 0 0
RM
Country [55] 0 0
Italy
State/province [55] 0 0
TO
Country [56] 0 0
Italy
State/province [56] 0 0
UD
Country [57] 0 0
Japan
State/province [57] 0 0
Aichi
Country [58] 0 0
Japan
State/province [58] 0 0
Fukuoka
Country [59] 0 0
Japan
State/province [59] 0 0
Hokkaido
Country [60] 0 0
Japan
State/province [60] 0 0
Hyogo
Country [61] 0 0
Japan
State/province [61] 0 0
Kanagawa
Country [62] 0 0
Japan
State/province [62] 0 0
Miyagi
Country [63] 0 0
Japan
State/province [63] 0 0
Okayama
Country [64] 0 0
Japan
State/province [64] 0 0
Osaka
Country [65] 0 0
Japan
State/province [65] 0 0
Tokyo
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Seoul
Country [67] 0 0
Netherlands
State/province [67] 0 0
The Netherlands
Country [68] 0 0
Norway
State/province [68] 0 0
Oslo
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Moscow
Country [70] 0 0
Saudi Arabia
State/province [70] 0 0
Riyadh
Country [71] 0 0
Spain
State/province [71] 0 0
Andalucia
Country [72] 0 0
Spain
State/province [72] 0 0
Asturias
Country [73] 0 0
Spain
State/province [73] 0 0
Catalunya
Country [74] 0 0
Spain
State/province [74] 0 0
Pontevedra
Country [75] 0 0
Spain
State/province [75] 0 0
Madrid
Country [76] 0 0
Spain
State/province [76] 0 0
Malaga
Country [77] 0 0
Spain
State/province [77] 0 0
Valencia
Country [78] 0 0
Taiwan
State/province [78] 0 0
Taichung
Country [79] 0 0
Turkey
State/province [79] 0 0
Ankara
Country [80] 0 0
Turkey
State/province [80] 0 0
Istanbul
Country [81] 0 0
Turkey
State/province [81] 0 0
Izmir
Country [82] 0 0
United Kingdom
State/province [82] 0 0
London
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
Assess the efficacy and safety of ruxolitinib compared to Best Available Therapy (BAT) in
patients with corticosteroid-refractory acute graft vs. host disease (aGvHD) after allogeneic
stem cell transplantation.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02913261
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02913261