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

Chronic Graft-versus-host Disease Clinical Trial

Official title:

GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03584516
• Other study ID #: INCB 39110-309
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: January 17, 2019
• Est. completion date: November 3, 2023

Study information

• Verified date: January 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 155
• Est. completion date: November 3, 2023
• Est. primary completion date: November 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiolitis Obliterans Syndrome
• Chronic Graft-versus-host Disease
• Graft vs Host Disease

Intervention

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.
• Placebo
In Part 2, participants will receive matching placebo.
• 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.
• 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.

Locations

Country	Name	City	State
Austria	Ordensklinikum Linz Gmbh Elisabethinen	Linz
Belgium	Zna Stuivenberg	Antwerpen
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen (Uza)	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven
Belgium	CENTRE HOSPITALIER UNIVERSITAIRE DE LI�GE - SART TILMAN	Liege
Belgium	AZ DELTA	Roeselare
Canada	University of Alberta	Edmonton	Alberta
Canada	Hospital Maisonneuve Rosemont	Montreal	Quebec
Canada	Saskatchewan Cancer	Saskatoon	Saskatchewan
Canada	University Health Network	Toronto	Ontario
Denmark	The Finsen Centre National Hospital	Copenhagen
Finland	Turku University Hospital	Turku
France	Chu Amiens Picardie - Hopital Sud	Amiens
France	Centre Hospitalier D'Angers	Angers
France	Chu de Grenoble - Hopital Albert Michallon	Grenoble Cedex
France	Institut Paoli-Calmettes	Marseille
France	Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu	Nantes
France	Chu de Nice - Hospital L Archet	Nice
France	Chu de Rennes - Hospital Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
France	Chru Hopitaux de Tours Hospital Bretonneau	Tours
France	Hopitaux de Brabois	Vandoeuvre Les Nancy
Germany	Charite Berlin	Berlin
Germany	Universitatsklinikum Bonn Aoer	Bonn
Germany	University Clinic Carl Gustav Carus Technical University Dresden	Dresden
Germany	Universitaetsklinikum Erlangen - Medizinische Klinik 5	Erlangen
Germany	Universitatsklinikum Essen	Essen
Germany	UNIVERSIT�TSKLINIKUM HALLE (SAALE)	Halle
Germany	University Medical Centre Hamburg-Eppendorf Centre of Oncology	Hamburg
Germany	Universitaetsklinikum Jena	Jena
Germany	Universitatsklinikum Koln	Koeln
Germany	Selbststandige Abteilung Fur Hamatologie Und Internistische Onkologie	Leipzig
Germany	Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii	Mainz
Germany	University Hospital Mannheim	Mannheim
Germany	Universitatsklinikum Munster	Muenster
Germany	Iii Medizinische Klinik Und Poliklinik Klinikum Rechts Der Isar Technische Universitat Munchen	Munich
Germany	Universitaetsmedizin Rostock	Rostock
Germany	Universitaetsklinikum in Tubingen	Tubingen
Greece	University Hospital of West Attica - Attikon	Chaidari
Greece	General Hospital of Thessaloniki G. Papanikolaou	Thessaloniki
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Hebrew University Medical Center Ein Karem Hadassah	Jerusalem
Israel	Rabin Medical Center - Beilinson Hospital	Petach Tiqwa
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv-yafo
Italy	CLINICA DI EMATOLOGIA, UNIVERSIT� POLITECNICA DELLE MARCHE	Ancona
Italy	Azienda Ospedaliera Papa Giovanni Xxiii	Bergamo
Italy	L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI	Bologna
Italy	Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia	Brescia
Italy	Azienda Policlinico Vittorio Emanuele	Catania
Italy	Fondazione Irccs Ca Granda Ospedale Maggiore	Milan
Italy	Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele	Milano
Italy	A.O.U. Di Modena - Policlinico	Modena
Italy	A.O.U. Federico Ii	Napoli
Italy	Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello"	Palermo
Italy	Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo	Pavia
Italy	Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti	Reggio Calabria
Italy	Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore	Roma
Italy	Universita Degli Studi Di Roma La Sapienza - Umberto I Policlinico Di Roma - Centro Di Ematologia	Roma
Italy	Irrcs Instituto Clinico Humanitas	Rozzano
Italy	I.R.C.C.S. Casa Sollievo Della Sofferenza	San Giovanni Rotondo
Italy	Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza	Torino
Italy	Azienda Ospedaliero-Universitaria Santa Maria Della Misericordia	Udine
Italy	Centro Ricerche Cliniche Di Verona (Crc)	Verona
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Oddzial W Gliwi	Gliwice
Poland	Szpital Kliniczny Przemienienia Panskiego	Poznan
Poland	Mtz Clinical Research Sp. Zo.O.	Warszawa
Spain	Institut Catala D Oncologia	Badalona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Hospital Universitario Virgen de Las Nieves	Granada
Spain	Ico Institut Catala D Oncologia	L'hospitalet de Llobregat
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Son Espases University Hospital	Palma
Spain	Clinica Universidad de Navarra (Cun)	Pamplona
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Clinico de Santiago de Compostela	Santiago de Compostela
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario Y Politcnico de La Fe	Valencia
Sweden	Karolinska University Hospital Huddinge	Huddinge
Sweden	Skane University Hospital Lund	Lund
Switzerland	Universitatsspital Zurich	Zurich
United Kingdom	Bristol Haematology & Oncology Centre	Bristol
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Barts Health Nhs Trust - St Bartholomews Hospital	London
United Kingdom	Imperial College Healthcare Nhs Trust - Hammersmith Hospital	London
United Kingdom	King'S College Hospital (Nhs Foundation)	London
United Kingdom	Nottingham University Hospitals Nhs Trust	Nottingham
United Kingdom	The Royal Marsden Nhs Foundation Trust - Sutton	Sutton
United Kingdom	St. George'S University Hospitals Nhs Foundation Trust	Tooting
United States	University of Michigan	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Augusta University - Medical College of Georgia	Augusta	Georgia
United States	St David'S South Austin Medical Center	Austin	Texas
United States	University of Maryland - Greenebaum Cancer Center	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Illinois Cancer Specialists	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Oncology Hematology Care, Inc	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology - Medical City Dallas	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Spectrum Health	Grand Rapids	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of California San Diego Medical Center, Moores Cancer Center	La Jolla	California
United States	University of Arkansas For Medical Sciences - Winthrop P Rockefeller Cancer Institute	Little Rock	Arkansas
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	University of Minnesota, Masonic Cancer Center	Minneapolis	Minnesota
United States	Tri Star Bone Marrow Transplant	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Tulane University	New Orleans	Louisiana
United States	Advocate Lutheran General Hospital - Oncology Specislists Sc	Park Ridge	Illinois
United States	Jefferson University Hospitals	Philadelphia	Pennsylvania
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	University of Rochester, James P. Wilmot Cancer Center	Rochester	New York
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	University of Arizona Cancer Center - Out Pt.	Tucson	Arizona
United States	University of Kansas Hospital Authority	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Part 1: Time to response	Defined as the interval between randomization and first response.	Up to 36 months
Other	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
Other	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
Other	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
Other	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
Primary	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
Primary	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
Primary	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	Part 1, 1 expansion, and Part 2: Cmax of itacitinib when administered in combination with corticosteroids	Maximum observed concentration.	Up to 28 days
Secondary	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