Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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9 January 2023 |
Main ID: |
EUCTR2016-004432-38-BE |
Date of registration:
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22/05/2017 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Study of efficacy and safety of ruxolitinib vs. best available therapy (BAT) in patients with corticosteroid refractory chronic graft versus host disease after bone marrow transplantation
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Scientific title:
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A phase III randomized open-label multi-center study of ruxolitinib vs. best available therapy in patients with corticosteroid-refractory chronic graft versus host disease after allogeneic stem cell transplantation - REACH 3 |
Date of first enrolment:
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21/08/2017 |
Target sample size:
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324 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004432-38 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Best Available Therapy (BAT) Number of treatment arms in the trial: 2
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Australia
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Austria
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Belgium
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Bulgaria
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Canada
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China
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Czech Republic
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Denmark
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France
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Germany
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Greece
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Hungary
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India
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Israel
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Italy
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Japan
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Jordan
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Korea, Republic of
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Netherlands
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Norway
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Poland
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Portugal
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Romania
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Russian Federation
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Saudi Arabia
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Spain
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Sweden
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Switzerland
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Turkey
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United Kingdom
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United States
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Contacts
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Name:
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Clinical Trial Information Desk
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Address:
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Forum 1, Novartis Campus
4056
Basel
Switzerland |
Telephone:
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+41 61 324 1111 |
Email:
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clinicaltrial.enquiries@novartis.com |
Affiliation:
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Novartis Pharma AG |
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Name:
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Clinical Trial Information Desk
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Address:
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Forum 1, Novartis Campus
4056
Basel
Switzerland |
Telephone:
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+41 61 324 1111 |
Email:
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clinicaltrial.enquiries@novartis.com |
Affiliation:
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Novartis Pharma AG |
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Key inclusion & exclusion criteria
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Inclusion criteria: ? Male or female patients =12 years old at the time of signing the ICF
? 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 non-myeloablative, myeloablative, and reduced intensity conditioning are eligible
? Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) >1000/mm3 and platelet count > 25,000/ mm3
? Patients with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria (Jagasia 2015) prior to randomization:
? Moderate cGvHD: At least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1
? Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3
? Patients currently receiving systemic or topical corticosteroids for the treatment of cGvHD for a duration of < 12 months prior to Cycle 1 Day 1
(if applicable), and have a confirmed diagnosis of steroid refractory cGvHD defined per 2014 NIH consensus criteria (Martin 2015) irrespective of the concomitant use of a calcineurin inhibitor, as follows:
? A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week (or equivalent), OR
? Disease persistence without improvement despite continued treatment with prednisone at >0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, (or equivalent) OR
? Increase to prednisone dose to >0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent)
? Patient must accept to be treated with only one of the following BAT options on Cycle 1 Day 1. (Additions and changes are allowed during the
course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX),
mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 132 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 162
Exclusion criteria: ? Patients who have received two or more systemic treatments (BAT) for cGvHD in addition to corticosteroids ± CNI for cGvHD
? Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment
? Patients who were treated with prior JAK inhibitors for aGvHD; except when the patient achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1
? Failed prior alloSCT within the past 6 months from Cycle 1 Day 1
? Patients with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed
? SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence.
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 cGvHD at doses >1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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corticosteroid refractory chronic Graft vs Host Disease MedDRA version: 20.1
Level: PT
Classification code 10072158
Term: Chronic graft versus host disease in intestine
System Organ Class: 10021428 - Immune system disorders
MedDRA version: 20.1
Level: PT
Classification code 10072159
Term: Chronic graft versus host disease in skin
System Organ Class: 10021428 - Immune system disorders
MedDRA version: 20.1
Level: PT
Classification code 10066261
Term: Chronic graft versus host disease
System Organ Class: 10021428 - Immune system disorders
MedDRA version: 20.1
Level: PT
Classification code 10072160
Term: Chronic graft versus host disease in liver
System Organ Class: 10021428 - Immune system disorders
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Therapeutic area: Diseases [C] - Cancer [C04]
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Intervention(s)
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Trade Name: Jakavi Product Name: ruxolitinib Product Code: INC424 Pharmaceutical Form: Tablet INN or Proposed INN: ruxolitinib CAS Number: 1092939-17-7 Current Sponsor code: INC424 Other descriptive name: RUXOLITINIB PHOSPHATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5-
Pharmaceutical Form:
Pharmaceutical Form:
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Primary Outcome(s)
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Secondary Objective: Key Secondary: To compare the rate of failure free survival (FFS) and the change in the modified Lee cGvHD Symptom Scale score between treatment groups
Other secondary: ? Best overall response (BOR) ? Estimate ORR at the end of Cycle 3 ? Duration of response ? Overall survival ? Non-relapse mortality (NRM) ? Proportion of patients with =50% reduction in the daily steroid dose at Cycle 7 Day 1 ? Proportion of patients who successfully tapered off all steroids at Cycle 7 Day 1 ? Cumulative incidence of Malignancy Relapse/Recurrence (MR) ? Change in FACT-BMT and EQ-5D ? To assess pharmacokinetics of ruxolitinib ? Safety and tolerability of ruxolitinib and BAT ? Medical resource utilization
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Timepoint(s) of evaluation of this end point: Cycle 7 Day 1
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Primary end point(s): overall response rate (ORR) on Cycle 7 Day 1 after randomization, defined as the proportion of patients in each arm demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ score at randomization.
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Main Objective: To compare the efficacy of ruxolitinib versus Investigator’s choice Best Available Therapy (BAT) in patients with moderate or severe SR-cGvHD assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 visit.
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Secondary Outcome(s)
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Timepoint(s) of evaluation of this end point: for all:
Cycle 7 Day 1
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Secondary end point(s): Key secondary:
Composite time to event endpoint incorporating the following FFS events:
i) relapse or recurrence of underlying disease or death due to underlying disease,
ii) non-relapse mortality, or
iii) addition or initiation of another systemic therapy for cGvHD
Rate of patients with clinically relevant improvement of
the modified Lee symptoms score at Cycle 7 Day 1.
FFS will be used as the first key secondary endpoint for all regions except the US (ROW). The modified Lee symptom score will be used as the first key secondary
endpoint for the US
Other secondary:
- Proportion of patients who achieved OR (CR+PR) at any time point (up Cycle 7 day 1 or the start of additional systemic therapy for cGvHD)
- To estimate ORR at end of Cycle 3 Proportion of patients who achieved OR (CR+PR) at Cycle 4 Day 1.
- Duration of Response Duration of response (DOR) is assessed for responders only
- Overall survival, defined as the time from the date of randomization to the date of death due to any cause
- Non-relapse mortality (NRM), defined as the time from date of randomization to date of death not preceded by underlying disease relapse/recurrence
- Malignancy Relapse/Recurrence (MR) is defined as the time from date of randomization to hematologic malignancy relapse/recurrence
- Change in FACT-BMT from baseline to each visit where measured.
- Change in EQ-5D from baseline to each visit where measured
- Pharmacokinetic parameters of ruxolitinib after a single dose and at steady state. Cmax, AUClast, and AUCinf. Other PK parameters are CL/F, Vz/F, Tmax and T1/2
- Safety and tolerability including myelosuppression, infections, and bleeding will be assessed by monitoring the frequency, duration, and severity of Adverse Events including occurrence of any second primary malignancies, infections, by performing physical exams, and evaluating changes in vital signs from baseline, routine serum chemistry, hematology results and coagulation profile
- Resources including duration and frequency of hospitalization, emergency room visits, additional outpatient office visits to general practitioner, specialist, and urgent care visits
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Secondary ID(s)
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2016-004432-38-GB
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CINC424D2301
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Source(s) of Monetary Support
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Novartis Pharma AG
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Ethics review
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Status: Approved
Approval date: 21/08/2017
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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