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

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).

Study Overview

• Status: Terminated
• Conditions: Chronic Graft-versus-host Disease
• Intervention / Treatment: Drug: Itacitinib; Drug: Methylprednisolone; Drug: Prednisone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 04020
    • Ordensklinikum Linz GmbH Elisabethinen
• Belgium
  • Antwerpen, Belgium, 02060
    • ZNA Stuivenberg
  • Brussels, Belgium, 01000
    • Institut Jules Bordet
  • Edegem, Belgium, 02650
    • Universitair Ziekenhuis Antwerpen (Uza)
  • Gent, Belgium, 09000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
  • Liege, Belgium, 04000
    • CENTRE HOSPITALIER UNIVERSITAIRE DE LI�GE - SART TILMAN
  • Roeselare, Belgium, 08800
    • AZ Delta
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2P4
      • University of Alberta
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hospital Maisonneuve Rosemont
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatchewan Cancer
• Denmark
  • Copenhagen, Denmark, 02100
    • The Finsen Centre National Hospital
• Finland
  • Turku, Finland, 20521
    • Turku University Hospital
• France
  • Amiens, France, 80054
    • CHU Amiens Picardie - Hopital Sud
  • Angers, France, 49000
    • Centre Hospitalier D'Angers
  • Grenoble Cedex, France, 38700
    • CHU de Grenoble - Hôpital Albert Michallon
  • Marseille, France, 13273
    • Institut Paoli-Calmettes
  • Nantes, France, 44000
    • Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
  • Nice, France, 06800
    • Chu de Nice - Hospital L Archet
  • Rennes, France, 35033
    • Chu de Rennes - Hospital Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Tours, France, 37000
    • Chru Hopitaux de Tours Hospital Bretonneau
  • Vandoeuvre Les Nancy, France, 54511
    • Hôpitaux de Brabois
• Germany
  • Berlin, Germany, 12200
    • Charite Berlin
  • Bonn, Germany, 00011
    • Universitatsklinikum Bonn Aoer
  • Dresden, Germany, 01307
    • University Clinic Carl Gustav Carus Technical University Dresden
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen - Medizinische Klinik 5
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Halle, Germany, D06120
    • UNIVERSIT�TSKLINIKUM HALLE (SAALE)
  • Hamburg, Germany, 20246
    • University Medical Centre Hamburg-Eppendorf Centre of Oncology
  • Jena, Germany, 07740
    • Universitaetsklinikum Jena
  • Koeln, Germany, 50937
    • Universitätsklinikum Köln
  • Leipzig, Germany, 00341
    • Selbststandige Abteilung Fur Hamatologie Und Internistische Onkologie
  • Mainz, Germany, 55131
    • Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
  • Mannheim, Germany, 68167
    • University Hospital Mannheim
  • Muenster, Germany, 48149
    • Universitätsklinikum Münster
  • Munich, Germany, 81675
    • Iii Medizinische Klinik Und Poliklinik Klinikum Rechts Der Isar Technische Universitat Munchen
  • Rostock, Germany, 18057
    • Universitaetsmedizin Rostock
  • Tubingen, Germany, 72076
    • Universitaetsklinikum in Tubingen
• Greece
  • Chaidari, Greece, 124 62
    • University Hospital of West Attica - Attikon
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki G. Papanikolaou
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Medical Center Ein Karem Hadassah
  • Petach Tiqwa, Israel, 49100
    • Rabin Medical Center - Beilinson Hospital
  • Tel Aviv-yafo, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Ancona, Italy, 60126
    • CLINICA DI EMATOLOGIA, UNIVERSIT� POLITECNICA DELLE MARCHE
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Catania, Italy, 95123
    • Azienda Policlinico Vittorio Emanuele
  • Milan, Italy, 20122
    • Fondazione Irccs Ca Granda Ospedale Maggiore
  • Milano, Italy, 20132
    • Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
  • Modena, Italy, 41124
    • A.O.U. di Modena - Policlinico
  • Napoli, Italy, 80131
    • A.O.U. Federico II
  • Palermo, Italy, 90100
    • Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello"
  • Pavia, Italy, 27100
    • Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
  • Reggio Calabria, Italy, 89133
    • Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti
  • Roma, Italy, 00161
    • Universita Degli Studi Di Roma La Sapienza - Umberto I Policlinico Di Roma - Centro Di Ematologia
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
  • Rozzano, Italy, 20089
    • Irrcs Instituto Clinico Humanitas
  • San Giovanni Rotondo, Italy, 71013
    • I.R.C.C.S. Casa Sollievo Della Sofferenza
  • Torino, Italy, 10126
    • Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
  • Udine, Italy, 33100
    • Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
  • Verona, Italy, 37134
    • Centro Ricerche Cliniche Di Verona (Crc)
• Poland
  • Gdansk, Poland, 80-592
    • Uniwersyteckie Centrum Kliniczne
  • Gliwice, Poland, 44-101
    • Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Oddzial W Gliwi
  • Poznan, Poland, 60-569
    • Szpital Kliniczny Przemienienia Pańskiego
  • Warszawa, Poland, 02-106
    • Mtz Clinical Research Sp. Zo.O.
• Spain
  • Badalona, Spain, 08916
    • Institut Catala D Oncologia
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de Las Nieves
  • L'hospitalet de Llobregat, Spain, 08908
    • Ico Institut Catala D Oncologia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Palma, Spain, 07120
    • Son Espases University Hospital
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra (Cun)
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Santiago de Compostela, Spain, 15706
    • Hospital Clínico de Santiago de Compostela
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46009
    • Hospital Universitario Y Politcnico de La Fe
• Sweden
  • Huddinge, Sweden, 141 86
    • Karolinska University Hospital Huddinge
  • Lund, Sweden, 22185
    • Skane University Hospital Lund
• Switzerland
  • Zurich, Switzerland, 08091
    • Universitätsspital Zürich
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology & Oncology Centre
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust - Hammersmith Hospital
  • London, United Kingdom, EC1A 7BE
    • Barts Health Nhs Trust - St Bartholomews Hospital
  • London, United Kingdom, SE5 9RS
    • King'S College Hospital (Nhs Foundation)
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Nhs Foundation Trust - Sutton
  • Tooting, United Kingdom, SW17 0QT
    • St. George's University Hospitals NHS Foundation Trust
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center - Out Pt.
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas For Medical Sciences - Winthrop P Rockefeller Cancer Institute
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • La Jolla, California, United States, 92093
      • University of California San Diego Medical Center, Moores Cancer Center
  • Florida
    • Miami, Florida, United States, 33136-1002
      • University of Miami Sylvester Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
    • Augusta, Georgia, United States, 30912
      • Augusta University - Medical College of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60714
      • Illinois Cancer Specialists
    • Maywood, Illinois, United States, 60153-3328
      • Loyola University Medical Center
    • Park Ridge, Illinois, United States, 60028
      • Advocate Lutheran General Hospital - Oncology Specislists Sc
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5201
      • Indiana University Melvin and Bren Simon Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66160
      • University of Kansas Hospital Authority
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-2618
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland - Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111-1552
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, Masonic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-8550
      • Hackensack University Medical Center
  • New York
    • Rochester, New York, United States, 14642-0001
      • University of Rochester, James P. Wilmot Cancer Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care, Inc
    • Cleveland, Ohio, United States, 44106-1716
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Abramson Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson University Hospitals
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15232-1309
      • University of Pittsburgh
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105-2108
      • Avera Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Tri Star Bone Marrow Transplant
  • Texas
    • Austin, Texas, United States, 78704
      • St David'S South Austin Medical Center
    • Dallas, Texas, United States, 75230
      • Texas Oncology - Medical City Dallas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Sammons Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 : Dose determination of itacitinib; itacitinib administered in combination with corticosteroids.	Drug: 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.; Other Names: INCB039110; 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.; Other Names: Medrol, Medrol Dosepak, Solu-Medrol; 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.; Other Names: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS
Experimental: Part 1 : Dose expansion of itacitinib; itacitinib administered in combination with corticosteroids or corticosteroids alone.	Drug: 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.; Other Names: INCB039110; 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.; Other Names: Medrol, Medrol Dosepak, Solu-Medrol; 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.; Other Names: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS; Drug: Placebo; In Part 2, participants will receive matching placebo.
Placebo Comparator: Part 2 : itacitinib recommended dose from part 1; itacitinib or placebo administered in combination with corticosteroids	Drug: 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.; Other Names: INCB039110; 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.; Other Names: Medrol, Medrol Dosepak, Solu-Medrol; 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.; Other Names: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 : Dose Determination: Number of dose-limiting toxicities	To identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe cGVHD.	28 days
Part 2 : Response rate	Defined as the proportion of participants demonstrating a complete response (CR) or partial response (PR) per National Institutes of Health (NIH) consensus guideline.	Month 6
Part 1 : Dose Expansion: Number of dose-limiting toxicities	To identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe cGVHD.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1, 1 expansion, and Part 2: Cmax of itacitinib when administered in combination with corticosteroids	Maximum observed concentration.	Up to 28 days
Part 1, 1 expansion, and Part 2: Cmin of itacitinib when administered in combination with corticosteroids	Minimum observed plasma or serum concentration over the dose interval.	Up to 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1, 1 expansion, and Part 2: Response rate	Defined as the proportion of participants who demonstrate a CR or PR per NIH consensus guideline.	Up to 12 months
Part 1: Time to response	Defined as the interval between randomization and first response.	Up to 36 months
Part 1, 1 expansion, and Part 2: Duration of response	Defined as the interval between first response and cGVHD progression, death, malignancy relapse, or initiation of new systemic cGVHD therapy.	Up to 36 months
Part 1, 1 expansion, and Part 2: Overall survival	Defined as the interval between the date of randomization and the date of death due to any cause.	Up to 36 months
Part 1, 1 expansion, and Part 2: Nonrelapse mortality	Defined as the proportion of participants who died due to causes other than malignancy relapse.	Up to 36 months
Part 2: Number of treatment-emergent adverse events	Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment).	Up to 36 months

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Rodica Morariu-Zamfir, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): November 3, 2023
• Study Completion (Actual): November 3, 2023

Study Registration Dates

• First Submitted: June 29, 2018
• First Submitted That Met QC Criteria: June 29, 2018
• First Posted (Actual): July 12, 2018

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: corticosteroids; Graft-versus-host-disease; itacitinib; Janus kinase inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone
• Other Study ID Numbers: INCB 39110-309

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No