A Study of Ruxolitinib vs Best Available Therapy (BAT) in Patients With Steroid-refractory Chronic Graft vs. Host Disease (GvHD) After Bone Marrow Transplantation (REACH3)
NCT ID: NCT03112603
Last Updated: 2025-08-12
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
330 participants
INTERVENTIONAL
2017-06-29
2022-12-15
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Ruxolitinib
Ruxolitinib for the treatment period and extension period.
Ruxolitinib
Ruxolitinib twice daily at the protocol-defined starting dose.
Best Available Therapy
Best available therapy for the treatment period and extension period, with optional crossover to ruxolitinib after Cycle 6.
Extracorporeal photopheresis (ECP)
Best available therapy (BAT) will be selected by the investigator for each participant. BAT may not include experimental agents (ie, those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. The BAT in this study will be among the following treatments currently used in this setting (no other types or combinations of BATs are permitted in this study).
Low-dose methotrexate (MTX)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Mycophenolate mofetil (MMF)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Infliximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Rituximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Pentostatin
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Imatinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Ibrutinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Interventions
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Ruxolitinib
Ruxolitinib twice daily at the protocol-defined starting dose.
Extracorporeal photopheresis (ECP)
Best available therapy (BAT) will be selected by the investigator for each participant. BAT may not include experimental agents (ie, those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. The BAT in this study will be among the following treatments currently used in this setting (no other types or combinations of BATs are permitted in this study).
Low-dose methotrexate (MTX)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Mycophenolate mofetil (MMF)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Infliximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Rituximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Pentostatin
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Imatinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Ibrutinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) \> 1000/mm\^3 and platelet count \> 25,000/ mm\^3
* Participants with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria 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
* Participants 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 irrespective of the concomitant use of a calcineurin inhibitor (CNI), as follows:
* A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, 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
* Increase to prednisolone dose to \> 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose
* Participant 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
Exclusion Criteria
* Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment
\* Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.
* Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant 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
* Participants with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed
* Steroid refractory cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for preemptive treatment of malignancy recurrence. Participants 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
12 Years
ALL
No
Sponsors
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Incyte Corporation
INDUSTRY
Responsible Party
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Principal Investigators
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Rodica Morariu-Zamfir
Role: STUDY_DIRECTOR
Incyte Corporation
Locations
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Incyte Investigative Site
Tucson, Arizona, United States
Incyte Investigative Site
Duarte, California, United States
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La Jolla, California, United States
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Los Angeles, California, United States
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New Haven, Connecticut, United States
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Wilmington, Delaware, United States
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Gainesville, Florida, United States
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Tampa, Florida, United States
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Chicago, Illinois, United States
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Chicago, Illinois, United States
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Chicago, Illinois, United States
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Maywood, Illinois, United States
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Indianapolis, Indiana, United States
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Westwood, Kansas, United States
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Lexington, Kentucky, United States
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Boston, Massachusetts, United States
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Boston, Massachusetts, United States
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Omaha, Nebraska, United States
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Hackensack, New Jersey, United States
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New York, New York, United States
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New York, New York, United States
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New York, New York, United States
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Chapel Hill, North Carolina, United States
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Durham, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Cincinnati, Ohio, United States
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Cleveland, Ohio, United States
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Cleveland, Ohio, United States
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Columbus, Ohio, United States
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Oklahoma City, Oklahoma, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Nashville, Tennessee, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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Seattle, Washington, United States
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Milwaukee, Wisconsin, United States
Novartis Investigative Site
Darlinghurst, New South Wales, Australia
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Parkville, Victoria, Australia
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Innsbruck, Tyrol, Austria
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Graz, , Austria
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Linz, , Austria
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Vienna, , Austria
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Antwerp, , Belgium
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Bruges, , Belgium
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Brussels, , Belgium
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Ghent, , Belgium
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Leuven, , Belgium
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Liège, , Belgium
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Sofia, , Bulgaria
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Sofia, , Bulgaria
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Vancouver, British Columbia, Canada
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Hamilton, Ontario, Canada
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Prague, Czech Republic, Czechia
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Hradec Králové, CZE, Czechia
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Prague, , Czechia
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Copenhagen, , Denmark
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Odense, , Denmark
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Bordeaux, Aquitaine, France
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Amiens Cedex1, , France
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Caen, , France
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Lille, , France
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Limoges, , France
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Lyon, , France
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Montpellier, , France
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Paris, , France
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Paris, , France
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Pierre-Benite Cédex, , France
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Rennes, , France
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Rouen, , France
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Saint-Priest-en-Jarez, , France
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Strasbourg, , France
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Toulouse, , France
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Vandœuvre-lès-Nancy, , France
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Mannheim, Baden-Wurttemberg, Germany
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Augsburg, , Germany
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Berlin, , Germany
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Cologne, , Germany
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Dresden, , Germany
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Düsseldorf, , Germany
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Erlangen, , Germany
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Essen, , Germany
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Frankfurt, , Germany
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Freiburg im Breisgau, , Germany
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Hamburg, , Germany
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Hamburg, , Germany
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Jena, , Germany
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Kiel, , Germany
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Leipzig, , Germany
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Mainz, , Germany
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Mannheim, , Germany
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Münster, , Germany
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Ulm, , Germany
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Würzburg, , Germany
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Athens, GR, Greece
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Pátrai, GR, Greece
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Thessaloniki, GR, Greece
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Athens, , Greece
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Budapest, , Hungary
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Navi Mumbai, Maharashtra, India
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Pune, Maharashtra, India
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Delhi, , India
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Vellore, , India
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Haifa, , Israel
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Jerusalem, , Israel
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Petah Tikva, , Israel
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Tel Aviv, , Israel
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Ancona, AN, Italy
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Bergamo, BG, Italy
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Bologna, BO, Italy
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Brescia, BS, Italy
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Genova, GE, Italy
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Genova, GE, Italy
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Milan, MI, Italy
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Rozzano, MI, Italy
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Palermo, PA, Italy
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Pescara, PE, Italy
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Parma, PR, Italy
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Pavia, PV, Italy
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Roma, RM, Italy
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Roma, RM, Italy
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Roma, RM, Italy
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Torino, TO, Italy
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Udine, UD, Italy
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Perugia, , Italy
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Nagoya, Aichi-ken, Japan
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Fukuoka, Fukuoka, Japan
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Sapporo, Hokkaido, Japan
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Kobe, Hyōgo, Japan
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Nishinomiya, Hyōgo, Japan
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Isehara, Kanagawa, Japan
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Sendai, Miyagi, Japan
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Osaka, Osaka, Japan
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Suita, Osaka, Japan
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Shimotsuke, Tochigi, Japan
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Bunkyō-ku, Tokyo, Japan
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Minato-ku, Tokyo, Japan
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Shinjuku-ku, Tokyo, Japan
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Kyoto, , Japan
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Okayama, , Japan
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Amman, , Jordan
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Utrecht, The Netherlands, Netherlands
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Leiden, , Netherlands
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Nijmegen, , Netherlands
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Rotterdam, , Netherlands
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Oslo, , Norway
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Wroclaw, Lower Silesian Voivodeship, Poland
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Gliwice, Silesian Voivodeship, Poland
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Katowice, , Poland
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Krakow, , Poland
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Warsaw, , Poland
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Lisbon, , Portugal
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Porto, , Portugal
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Ponce, , Puerto Rico
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Bucharest, , Romania
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Bucharest, , Romania
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Moscow, , Russia
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Saint Petersburg, , Russia
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Riyadh, , Saudi Arabia
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Seoul, , South Korea
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Seoul, , South Korea
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Córdoba, Andalusia, Spain
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Seville, Andalusia, Spain
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Donostia / San Sebastian, Basque Country, Spain
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Salamanca, Castille and León, Spain
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Barcelona, Catalonia, Spain
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Barcelona, Catalonia, Spain
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L'Hospitalet de Llobregat, Catalonia, Spain
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Santiago de Compostela, Galicia, Spain
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El Palmar, Murica, Spain
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Valencia, Valencia, Spain
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Barcelona, , Spain
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Las Palmas de Gran Canaria, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Gothenburg, , Sweden
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Uppsala, , Sweden
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Basel, , Switzerland
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Zurich, , Switzerland
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Ankara, , Turkey (Türkiye)
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Ankara, , Turkey (Türkiye)
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Antalya, , Turkey (Türkiye)
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Glasgow, , United Kingdom
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London, , United Kingdom
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London, , United Kingdom
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Manchester, , United Kingdom
Countries
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References
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Zeiser R, Russo D, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hamad N, Burock K, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F. Ruxolitinib in Patients With Corticosteroid-Refractory or Corticosteroid-Dependent Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of the Phase III REACH3 Study. J Clin Oncol. 2025 Aug 10;43(23):2566-2571. doi: 10.1200/JCO-24-02477. Epub 2025 Jun 25.
Mahmoudjafari Z, Kintsch E, Xue Z, Bhatt V, Galvin J, Locatelli F, Zeiser R. Impact of concomitant azoles on ruxolitinib treatment in patients with GVHD: post hoc analyses of REACH2 and REACH3. Blood Adv. 2025 Aug 26;9(16):4206-4216. doi: 10.1182/bloodadvances.2025016212.
Le RQ, Wang X, Zhang H, Li H, Przepiorka D, Vallejo J, Leong R, Ma L, Goldberg KB, Pazdur R, Theoret MR, De Claro A. FDA Approval Summary: Ruxolitinib for Treatment of Chronic Graft-Versus-Host Disease after Failure of One or Two Lines of Systemic Therapy. Oncologist. 2022 Jun 8;27(6):493-500. doi: 10.1093/oncolo/oyac042.
Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F; REACH3 Investigators. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2021 Jul 15;385(3):228-238. doi: 10.1056/NEJMoa2033122.
Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbaw B, Bubnoff NV. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Immunotherapy. 2018 Apr;10(5):391-402. doi: 10.2217/imt-2017-0156. Epub 2018 Jan 10.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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CINC424D2301
Identifier Type: OTHER
Identifier Source: secondary_id
2016-004432-38
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
INCB 18424-365 (REACH3)
Identifier Type: -
Identifier Source: org_study_id
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