GRAVITAS-309: Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease

NCT ID: NCT03584516

Last Updated: 2025-10-20

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

155 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-17

Study Completion Date

2023-11-03

Brief Summary

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The purpose of this study is to assess the efficacy and safety of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe chronic graft-versus-host disease (cGVHD).

Detailed Description

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Conditions

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Chronic Graft-versus-host Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

In Part 2 of the study, participants in the placebo group will be allowed to cross over to the experimental group after completion of the primary analysis.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Part 1 : Dose determination of itacitinib

itacitinib administered in combination with corticosteroids.

Group Type EXPERIMENTAL

Itacitinib

Intervention Type DRUG

In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion.

Methylprednisolone

Intervention Type DRUG

Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Prednisone

Intervention Type DRUG

Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Part 1 : Dose expansion of itacitinib

itacitinib administered in combination with corticosteroids or corticosteroids alone.

Group Type EXPERIMENTAL

Itacitinib

Intervention Type DRUG

In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion.

Placebo

Intervention Type DRUG

In Part 2, participants will receive matching placebo.

Methylprednisolone

Intervention Type DRUG

Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Prednisone

Intervention Type DRUG

Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Part 2 : itacitinib recommended dose from part 1

itacitinib or placebo administered in combination with corticosteroids

Group Type PLACEBO_COMPARATOR

Itacitinib

Intervention Type DRUG

In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion.

Methylprednisolone

Intervention Type DRUG

Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Prednisone

Intervention Type DRUG

Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Interventions

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Itacitinib

In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion.

Intervention Type DRUG

Placebo

In Part 2, participants will receive matching placebo.

Intervention Type DRUG

Methylprednisolone

Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Intervention Type DRUG

Prednisone

Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Intervention Type DRUG

Other Intervention Names

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INCB039110 Medrol, Medrol Dosepak, Solu-Medrol Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS

Eligibility Criteria

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Inclusion Criteria

* Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria
* Underwent allogeneic stem cell transplantation (allo-HCT)
* Karnofsky Performance Status score ≥ 60%.
* Evidence of myeloid and platelet engraftment.
* Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.

Exclusion Criteria

* Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD.
* Has received any other systemic treatment for cGVHD, including extracorporeal photopheresis (ECP).
* Prior treatment with a Janus kinase (JAK) inhibitor for acute GVHD, unless the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks before randomization.
* cGVHD occurring after a nonscheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence.
* Evidence of relapsed primary malignancy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rodica Morariu-Zamfir, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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University of Arizona Cancer Center - Out Pt.

Tucson, Arizona, United States

Site Status

University of Arkansas For Medical Sciences - Winthrop P Rockefeller Cancer Institute

Little Rock, Arkansas, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

University of California San Diego Medical Center, Moores Cancer Center

La Jolla, California, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Augusta University - Medical College of Georgia

Augusta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Illinois Cancer Specialists

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Advocate Lutheran General Hospital - Oncology Specislists Sc

Park Ridge, Illinois, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Kansas Hospital Authority

Westwood, Kansas, United States

Site Status

Tulane University

New Orleans, Louisiana, United States

Site Status

University of Maryland - Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Spectrum Health

Grand Rapids, Michigan, United States

Site Status

University of Minnesota, Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Saint Louis University Cancer Center

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

University of Rochester, James P. Wilmot Cancer Center

Rochester, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Oncology Hematology Care, Inc

Cincinnati, Ohio, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Jefferson University Hospitals

Philadelphia, Pennsylvania, United States

Site Status

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

Tri Star Bone Marrow Transplant

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

St David'S South Austin Medical Center

Austin, Texas, United States

Site Status

Texas Oncology - Medical City Dallas

Dallas, Texas, United States

Site Status

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Ordensklinikum Linz Gmbh Elisabethinen

Linz, , Austria

Site Status

Zna Stuivenberg

Antwerp, , Belgium

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen (Uza)

Edegem, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Universitaire Ziekenhuis Leuven - Gasthuisberg

Leuven, , Belgium

Site Status

CENTRE HOSPITALIER UNIVERSITAIRE DE LI�GE - SART TILMAN

Liège, , Belgium

Site Status

AZ DELTA

Roeselare, , Belgium

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

University Health Network

Toronto, Ontario, Canada

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Hospital Maisonneuve Rosemont

Montreal, Quebec, Canada

Site Status

Saskatchewan Cancer

Saskatoon, Saskatchewan, Canada

Site Status

The Finsen Centre National Hospital

Copenhagen, , Denmark

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Turku University Hospital

Turku, , Finland

Site Status

Chu Amiens Picardie - Hopital Sud

Amiens, , France

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Centre Hospitalier D'Angers

Angers, , France

Site Status

Chu de Grenoble - Hopital Albert Michallon

Grenoble, , France

Site Status

Institut Paoli-Calmettes

Marseille, , France

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Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu

Nantes, , France

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Chu de Nice - Hospital L Archet

Nice, , France

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Chu de Rennes - Hospital Pontchaillou

Rennes, , France

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Centre Henri Becquerel

Rouen, , France

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Chru Hopitaux de Tours Hospital Bretonneau

Tours, , France

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Hopitaux de Brabois

Vandœuvre-lès-Nancy, , France

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Charite Berlin

Berlin, , Germany

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Universitatsklinikum Bonn Aoer

Bonn, , Germany

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Universitatsklinikum Koln

Cologne, , Germany

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University Clinic Carl Gustav Carus Technical University Dresden

Dresden, , Germany

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Universitaetsklinikum Erlangen - Medizinische Klinik 5

Erlangen, , Germany

Site Status

Universitatsklinikum Essen

Essen, , Germany

Site Status

UNIVERSIT�TSKLINIKUM HALLE (SAALE)

Halle, , Germany

Site Status

University Medical Centre Hamburg-Eppendorf Centre of Oncology

Hamburg, , Germany

Site Status

Universitaetsklinikum Jena

Jena, , Germany

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Selbststandige Abteilung Fur Hamatologie Und Internistische Onkologie

Leipzig, , Germany

Site Status

Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii

Mainz, , Germany

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University Hospital Mannheim

Mannheim, , Germany

Site Status

Iii Medizinische Klinik Und Poliklinik Klinikum Rechts Der Isar Technische Universitat Munchen

Munich, , Germany

Site Status

Universitatsklinikum Munster

Münster, , Germany

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Universitaetsmedizin Rostock

Rostock, , Germany

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Universitaetsklinikum in Tubingen

Tübingen, , Germany

Site Status

University Hospital of West Attica - Attikon

Chaïdári, , Greece

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General Hospital of Thessaloniki G. Papanikolaou

Thessaloniki, , Greece

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Rambam Medical Center

Haifa, , Israel

Site Status

Hadassah Hebrew University Medical Center Ein Karem Hadassah

Jerusalem, , Israel

Site Status

Rabin Medical Center - Beilinson Hospital

Petach Tiqwa, , Israel

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Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

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CLINICA DI EMATOLOGIA, UNIVERSIT� POLITECNICA DELLE MARCHE

Ancona, , Italy

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Azienda Ospedaliera Papa Giovanni Xxiii

Bergamo, , Italy

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L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI

Bologna, , Italy

Site Status

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, , Italy

Site Status

Azienda Policlinico Vittorio Emanuele

Catania, , Italy

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Fondazione Irccs Ca Granda Ospedale Maggiore

Milan, , Italy

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Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele

Milan, , Italy

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A.O.U. Di Modena - Policlinico

Modena, , Italy

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A.O.U. Federico Ii

Napoli, , Italy

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Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello"

Palermo, , Italy

Site Status

Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo

Pavia, , Italy

Site Status

Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti

Reggio Calabria, , Italy

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Universita Degli Studi Di Roma La Sapienza - Umberto I Policlinico Di Roma - Centro Di Ematologia

Roma, , Italy

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Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore

Roma, , Italy

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Irrcs Instituto Clinico Humanitas

Rozzano, , Italy

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I.R.C.C.S. Casa Sollievo Della Sofferenza

San Giovanni Rotondo, , Italy

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Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza

Torino, , Italy

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Azienda Ospedaliero-Universitaria Santa Maria Della Misericordia

Udine, , Italy

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Centro Ricerche Cliniche Di Verona (Crc)

Verona, , Italy

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Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

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Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Oddzial W Gliwi

Gliwice, , Poland

Site Status

Szpital Kliniczny Przemienienia Panskiego

Poznan, , Poland

Site Status

Mtz Clinical Research Sp. Zo.O.

Warsaw, , Poland

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Institut Catala D Oncologia

Badalona, , Spain

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Hospital de La Santa Creu I Sant Pau

Barcelona, , Spain

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Hospital Universitario Virgen de Las Nieves

Granada, , Spain

Site Status

Ico Institut Catala D Oncologia

L'Hospitalet de Llobregat, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

Hospital Universitario Ramon Y Cajal

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

Son Espases University Hospital

Palma, , Spain

Site Status

Clinica Universidad de Navarra (Cun)

Pamplona, , Spain

Site Status

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status

Hospital Clinico de Santiago de Compostela

Santiago de Compostela, , Spain

Site Status

Hospital Universitario Y Politcnico de La Fe

Valencia, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Karolinska University Hospital Huddinge

Huddinge, , Sweden

Site Status

Skane University Hospital Lund

Lund, , Sweden

Site Status

Universitatsspital Zurich

Zurich, , Switzerland

Site Status

Bristol Haematology & Oncology Centre

Bristol, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

Barts Health Nhs Trust - St Bartholomews Hospital

London, , United Kingdom

Site Status

King'S College Hospital (Nhs Foundation)

London, , United Kingdom

Site Status

Imperial College Healthcare Nhs Trust - Hammersmith Hospital

London, , United Kingdom

Site Status

Nottingham University Hospitals Nhs Trust

Nottingham, , United Kingdom

Site Status

The Royal Marsden Nhs Foundation Trust - Sutton

Sutton, , United Kingdom

Site Status

St. George'S University Hospitals Nhs Foundation Trust

Tooting, , United Kingdom

Site Status

Countries

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United States Austria Belgium Canada Denmark Finland France Germany Greece Israel Italy Poland Spain Sweden Switzerland United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-001606-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 39110-309

Identifier Type: -

Identifier Source: org_study_id

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