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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02913261
Ethics application status
Date submitted
18/09/2016
Date registered
23/09/2016
Date last updated
21/05/2021

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
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
Treatment: Drugs - Best Available Therapy (BAT)

Active Comparator: Ruxolitinib - Ruxolitinib 10 mg Bis In Diem (BID)

Active Comparator: Best Available Therapy (BAT) - As selected by the investigator


Treatment: Drugs: Ruxolitinib
Tablet for oral use

Treatment: Drugs: Best Available Therapy (BAT)
Best Available Therapy

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

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) - ORR is defined as the proportion of patients with a best overall response defined as complete response or partial response
Timepoint [1] 0 0
28 Days
Secondary outcome [1] 0 0
Durable Overall Response Rate - Proportion of all patients in each arm who achieve a complete response (CR) or partial response (PR) at Day 28 (primary endpoint) AND maintain a CR or PR at Day 56.
Timepoint [1] 0 0
Day 56
Secondary outcome [2] 0 0
ORR - Proportion of patients who achieved OR (CR+PR) at Day 14
Timepoint [2] 0 0
Day 14
Secondary outcome [3] 0 0
Duration of response (DOR) - DOR is the time from first response until acute Graft versus Host Disease (aGvHD) progression or the date of additional systemic therapies for aGvHD.
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Cumulative steroid dose - Weekly cumulative steroid dose for each subject up to Day 56 or end of treatment
Timepoint [4] 0 0
56 Days
Secondary outcome [5] 0 0
Overall Survival (OS) - OS is defined as the time from the date of randomization to the date of death due to any cause.
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [6] 0 0
Event-free survival - Event-free survival, defined as the time from the date of randomization to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.
Timepoint [6] 0 0
Up to 24 months
Secondary outcome [7] 0 0
Failure-Free survival (FFS) - FFS is defined as the time from the date of randomization to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment.
Timepoint [7] 0 0
Up to 24 months
Secondary outcome [8] 0 0
Non Relapse Mortality (NRM) - NRM is defined as the time from date of randomization to date of death not preceded by hematologic disease relapse/progression
Timepoint [8] 0 0
Up to 24 months
Secondary outcome [9] 0 0
Malignancy Relapse/Progression (MR) - MR is defined as the time from date of randomization to hematologic malignancy relapse/progression. Calculated for patients with underlying hematologic malignant disease.
Timepoint [9] 0 0
Up to 24 months
Secondary outcome [10] 0 0
Incidence of chronic Graft versus Host Disease (cGvHD) - cGvHD, defined as the diagnosis of any cGvHD including mild, moderate, severe
Timepoint [10] 0 0
Up to 24 months
Secondary outcome [11] 0 0
Pharmacokinetic (PK) parameter: Plasma concentration at peak (CMax) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients - plasma concentration at peak (Cmax)Ruxolitinib after a single dose and at steady state
Timepoint [11] 0 0
168 Days
Secondary outcome [12] 0 0
Exposure-efficacy relationship of ruxolitinib in corticosteroid refractory aGvHD - exposure-efficacy relationship of ruxolitinib in terms of concentration-effect and dose-effect (effect: overall response rate at Day 28 and durable response at Day 56; Overall survival at 6 months)
Timepoint [12] 0 0
168 Days
Secondary outcome [13] 0 0
Patient Reported Outcomes (PROs): Functional Assesment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) - Change in Functional Assesment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) from baseline
Timepoint [13] 0 0
Baseline, Up to 30 day follow-up visit
Secondary outcome [14] 0 0
Patient Reported Outcomes (PROs): EuroQol-5D-5L change - Change in EuroQol-5D-5D from baseline
Timepoint [14] 0 0
Baseline, Up to 30 day follow-up visit
Secondary outcome [15] 0 0
Pharmacokinetic (PK) parameter: Area Under the Curve (AUC) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients - AUC from time zero to the last measurable concentration sampling time and from time zero to infinity, and Accumulation ratio (Racc). Ruxolitinib after a single dose and at steady state. AUC at end of a dosing interval (AUC tau) at steady state.
Timepoint [15] 0 0
168 Days
Secondary outcome [16] 0 0
Pharmacokinetic (PK) parameter: total body clearance of ruxolitinib from the plasma after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients - total body clearance of ruxolitinib from the plasma after a single dose and at steady state
Timepoint [16] 0 0
168 Days
Secondary outcome [17] 0 0
Pharmacokinetic (PK) parameter: apparent volume of distribution during terminal phase after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients - apparent volume of distribution during terminal phase after a single dose and at steady state
Timepoint [17] 0 0
168 Days
Secondary outcome [18] 0 0
Best Overall Response (BOR) - Proportion of patients who achieved OR (CR+PR) at any time point up to and including Day 28 and before the start of additional systemic therapy for aGvHD.
Timepoint [18] 0 0
up to day 28
Secondary outcome [19] 0 0
Pharmacokinetic (PK) parameter: Ctough - Minimum concentration (Ctough) of ruxolitininb after a single dose and at steady state in corticosteroid refractory acute GVHD patients
Timepoint [19] 0 0
168 Days

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
Gender
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.

Other protocol-defined inclusion/exclusion criteria may apply.

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 3
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
To evaluate the safety and efficacy of ruxolitinib compared to Best Available Therapy in
patients with corticosteroid-refractory acute graft vs. host disease after allogeneic stem
cell transplantation
Trial website
https://clinicaltrials.gov/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
Other publications