Study Stopped
The study was terminated due to insufficient efficacy to support moving into Part 2 of the study; there were no safety concerns that contributed to this decision.
GRAVITAS-309: Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
2 other identifiers
interventional
155
16 countries
133
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2019
Longer than P75 for phase_2
133 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 29, 2018
CompletedFirst Posted
Study publicly available on registry
July 12, 2018
CompletedStudy Start
First participant enrolled
January 17, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 3, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 3, 2023
CompletedResults Posted
Study results publicly available
January 27, 2025
CompletedOctober 20, 2025
October 1, 2025
4.8 years
June 29, 2018
October 8, 2024
October 15, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
A DLT was defined as the occurrence of any protocol-defined toxicity with onset up to and including Day 28, except those with a clear alternative explanation. Participants who received at least 21 of 28 doses of study drug at the level assigned or had a DLT were considered evaluable for determining tolerability of the dose. Participants who did not achieve this duration of exposure and did not have a DLT were to be replaced for purposes of toxicity identification.
up to Day 28
Part 1 Expansion: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
until at least 30 days after the last dose of study treatment (up to 1103 days)
Part 2: Response Rate at Month 6
Response rate was defined as the percentage of participants that had complete response (CR) or partial response (PR), per National Institutes of Health (NIH) Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
Month 6
Secondary Outcomes (34)
Part 1 Expansion: Response Rate at Months 3 and 6
Months 3 and 6
Parts 1 and 1 Expansion: Cmax of Itacitinib
Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Parts 1 and 1 Expansion: Ctau of Itacitinib
Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
Parts 1 and 1 Expansion: Tmax of Itacitinib
Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
Parts 1 and 1 Expansion: Cl/F of Itacitinib
Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
- +29 more secondary outcomes
Study Arms (3)
Part 1 : Dose determination of itacitinib
EXPERIMENTALitacitinib administered in combination with corticosteroids.
Part 1 : Dose expansion of itacitinib
EXPERIMENTALitacitinib administered in combination with corticosteroids or corticosteroids alone.
Part 2 : itacitinib recommended dose from part 1
PLACEBO COMPARATORitacitinib or placebo administered in combination with corticosteroids
Interventions
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.
In Part 2, participants will receive matching placebo.
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (133)
University of Arizona Cancer Center - Out Pt.
Tucson, Arizona, 85724, United States
University of Arkansas For Medical Sciences - Winthrop P Rockefeller Cancer Institute
Little Rock, Arkansas, 72205, United States
City of Hope National Medical Center
Duarte, California, 91010, United States
University of California San Diego Medical Center, Moores Cancer Center
La Jolla, California, 92093, United States
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136-1002, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322, United States
Augusta University - Medical College of Georgia
Augusta, Georgia, 30912, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Illinois Cancer Specialists
Chicago, Illinois, 60714, United States
Loyola University Medical Center
Maywood, Illinois, 60153-3328, United States
Advocate Lutheran General Hospital - Oncology Specislists Sc
Park Ridge, Illinois, 60028, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202-5201, United States
University of Kansas Hospital Authority
Westwood, Kansas, 66160, United States
Tulane University
New Orleans, Louisiana, 70112-2618, United States
University of Maryland - Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Tufts Medical Center
Boston, Massachusetts, 02111-1552, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Spectrum Health
Grand Rapids, Michigan, 49503, United States
University of Minnesota, Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Saint Louis University Cancer Center
St Louis, Missouri, 63110, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601-8550, United States
University of Rochester, James P. Wilmot Cancer Center
Rochester, New York, 14642-0001, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Oncology Hematology Care, Inc
Cincinnati, Ohio, 45236, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106-1716, United States
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Jefferson University Hospitals
Philadelphia, Pennsylvania, 19107, United States
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15232-1309, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105-2108, United States
Tri Star Bone Marrow Transplant
Nashville, Tennessee, 37203, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
St David'S South Austin Medical Center
Austin, Texas, 78704, United States
Texas Oncology - Medical City Dallas
Dallas, Texas, 75230, United States
Texas Oncology - Baylor Sammons Cancer Center
Dallas, Texas, 75246, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Ordensklinikum Linz Gmbh Elisabethinen
Linz, 04020, Austria
Zna Stuivenberg
Antwerp, 02060, Belgium
Institut Jules Bordet
Brussels, 01000, Belgium
Universitair Ziekenhuis Antwerpen (Uza)
Edegem, 02650, Belgium
Universitair Ziekenhuis Gent
Ghent, 09000, Belgium
Universitaire Ziekenhuis Leuven - Gasthuisberg
Leuven, 03000, Belgium
CENTRE HOSPITALIER UNIVERSITAIRE DE LI�GE - SART TILMAN
Liège, 04000, Belgium
AZ DELTA
Roeselare, 08800, Belgium
University of Alberta
Edmonton, Alberta, T6G 2P4, Canada
University Health Network
Toronto, Ontario, M5G 2M9, Canada
Hospital Maisonneuve Rosemont
Montreal, Quebec, H1T 2M4, Canada
Saskatchewan Cancer
Saskatoon, Saskatchewan, S7N 4H4, Canada
The Finsen Centre National Hospital
Copenhagen, 02100, Denmark
Turku University Hospital
Turku, 20521, Finland
Chu Amiens Picardie - Hopital Sud
Amiens, 80054, France
Centre Hospitalier D'Angers
Angers, 49000, France
Chu de Grenoble - Hopital Albert Michallon
Grenoble, 38700, France
Institut Paoli-Calmettes
Marseille, 13273, France
Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
Nantes, 44000, France
Chu de Nice - Hospital L Archet
Nice, 06800, France
Chu de Rennes - Hospital Pontchaillou
Rennes, 35033, France
Centre Henri Becquerel
Rouen, 76038, France
Chru Hopitaux de Tours Hospital Bretonneau
Tours, 37000, France
Hopitaux de Brabois
Vandœuvre-lès-Nancy, 54511, France
Charite Berlin
Berlin, 12200, Germany
Universitatsklinikum Bonn Aoer
Bonn, 00011, Germany
Universitatsklinikum Koln
Cologne, 50937, Germany
University Clinic Carl Gustav Carus Technical University Dresden
Dresden, 01307, Germany
Universitaetsklinikum Erlangen - Medizinische Klinik 5
Erlangen, 91054, Germany
Universitatsklinikum Essen
Essen, 45147, Germany
UNIVERSIT�TSKLINIKUM HALLE (SAALE)
Halle, D06120, Germany
University Medical Centre Hamburg-Eppendorf Centre of Oncology
Hamburg, 20246, Germany
Universitaetsklinikum Jena
Jena, 07740, Germany
Selbststandige Abteilung Fur Hamatologie Und Internistische Onkologie
Leipzig, 00341, Germany
Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
Mainz, 55131, Germany
University Hospital Mannheim
Mannheim, 68167, Germany
Iii Medizinische Klinik Und Poliklinik Klinikum Rechts Der Isar Technische Universitat Munchen
Munich, 81675, Germany
Universitatsklinikum Munster
Münster, 48149, Germany
Universitaetsmedizin Rostock
Rostock, 18057, Germany
Universitaetsklinikum in Tubingen
Tübingen, 72076, Germany
University Hospital of West Attica - Attikon
Chaïdári, 124 62, Greece
General Hospital of Thessaloniki G. Papanikolaou
Thessaloniki, 57010, Greece
Rambam Medical Center
Haifa, 3109601, Israel
Hadassah Hebrew University Medical Center Ein Karem Hadassah
Jerusalem, 91120, Israel
Rabin Medical Center - Beilinson Hospital
Petach Tiqwa, 49100, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
CLINICA DI EMATOLOGIA, UNIVERSIT� POLITECNICA DELLE MARCHE
Ancona, 60126, Italy
Azienda Ospedaliera Papa Giovanni Xxiii
Bergamo, 24127, Italy
L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI
Bologna, 40138, Italy
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Brescia, 25123, Italy
Azienda Policlinico Vittorio Emanuele
Catania, 95123, Italy
Fondazione Irccs Ca Granda Ospedale Maggiore
Milan, 20122, Italy
Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
Milan, 20132, Italy
A.O.U. Di Modena - Policlinico
Modena, 41124, Italy
A.O.U. Federico Ii
Napoli, 80131, Italy
Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello"
Palermo, 90100, Italy
Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
Pavia, 27100, Italy
Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti
Reggio Calabria, 89133, Italy
Universita Degli Studi Di Roma La Sapienza - Umberto I Policlinico Di Roma - Centro Di Ematologia
Roma, 00161, Italy
Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
Roma, 00168, Italy
Irrcs Instituto Clinico Humanitas
Rozzano, 20089, Italy
I.R.C.C.S. Casa Sollievo Della Sofferenza
San Giovanni Rotondo, 71013, Italy
Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
Torino, 10126, Italy
Azienda Ospedaliero-Universitaria Santa Maria Della Misericordia
Udine, 33100, Italy
Centro Ricerche Cliniche Di Verona (Crc)
Verona, 37134, Italy
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-592, Poland
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Oddzial W Gliwi
Gliwice, 44-101, Poland
Szpital Kliniczny Przemienienia Panskiego
Poznan, 60-569, Poland
Mtz Clinical Research Sp. Zo.O.
Warsaw, 02-106, Poland
Institut Catala D Oncologia
Badalona, 08916, Spain
Hospital de La Santa Creu I Sant Pau
Barcelona, 08041, Spain
Hospital Universitario Virgen de Las Nieves
Granada, 18014, Spain
Ico Institut Catala D Oncologia
L'Hospitalet de Llobregat, 08908, Spain
Hospital General Universitario Gregorio Maranon
Madrid, 28007, Spain
Hospital Universitario Ramon Y Cajal
Madrid, 28034, Spain
Hospital Regional Universitario de Malaga
Málaga, 29010, Spain
Son Espases University Hospital
Palma, 07120, Spain
Clinica Universidad de Navarra (Cun)
Pamplona, 31008, Spain
Hospital Clinico Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Universitario Marques de Valdecilla
Santander, 39008, Spain
Hospital Clinico de Santiago de Compostela
Santiago de Compostela, 15706, Spain
Hospital Universitario Y Politcnico de La Fe
Valencia, 46009, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Karolinska University Hospital Huddinge
Huddinge, 141 86, Sweden
Skane University Hospital Lund
Lund, 22185, Sweden
Universitatsspital Zurich
Zurich, 08091, Switzerland
Bristol Haematology & Oncology Centre
Bristol, BS2 8ED, United Kingdom
University Hospital of Wales
Cardiff, CF14 4XW, United Kingdom
Barts Health Nhs Trust - St Bartholomews Hospital
London, EC1A 7BE, United Kingdom
King'S College Hospital (Nhs Foundation)
London, SE5 9RS, United Kingdom
Imperial College Healthcare Nhs Trust - Hammersmith Hospital
London, W12 0HS, United Kingdom
Nottingham University Hospitals Nhs Trust
Nottingham, NG5 1PB, United Kingdom
The Royal Marsden Nhs Foundation Trust - Sutton
Sutton, SM2 5PT, United Kingdom
St. George'S University Hospitals Nhs Foundation Trust
Tooting, SW17 0QT, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Based on preliminary data, Part 2 did not enroll participants. All participants in Part 1 Expansion who were on treatment with either itacitinib 300 or 400 milligrams (mg) once daily (QD) and who were tolerating and continuing to receive benefit from itacitinib had the option to continue itacitinib treatment in the INCB 39110-801 (NCT04640025) roll-over study.
Results Point of Contact
- Title
- Study Director
- Organization
- Incyte Corporation
Study Officials
- STUDY DIRECTOR
Rodica Morariu-Zamfir, MD
Incyte Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 29, 2018
First Posted
July 12, 2018
Study Start
January 17, 2019
Primary Completion
November 3, 2023
Study Completion
November 3, 2023
Last Updated
October 20, 2025
Results First Posted
January 27, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
- Access Criteria
- Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency