Clinical trial NCT03584516: GRAVITAS-309: Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
Official title: GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Chronic Graft-versus-host Disease
Keywords: Graft-versus-host-disease
itacitinib
Janus kinase inhibitor
corticosteroids
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-07-12
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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 purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: up to Day 28
measure: Part 1 Expansion: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: until at least 30 days after the last dose of study treatment (up to 1103 days)
measure: Part 2: Response Rate at Month 6
timeFrame: Month 6
Secondary outcomes:
measure: Part 1 Expansion: Response Rate at Months 3 and 6
timeFrame: Months 3 and 6
measure: Parts 1 and 1 Expansion: Cmax of Itacitinib
timeFrame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
measure: Parts 1 and 1 Expansion: Ctau of Itacitinib
timeFrame: 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)
measure: Parts 1 and 1 Expansion: Tmax of Itacitinib
timeFrame: 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)
measure: Parts 1 and 1 Expansion: Cl/F of Itacitinib
timeFrame: 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)
measure: Part 2: Cmax of Itacitinib
timeFrame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
measure: Part 2: Cmin of Itacitinib
timeFrame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
measure: Part 2: Tmax of Itacitinib
timeFrame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
measure: Part 2: AUC0-t of Itacitinib
timeFrame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
measure: Part 2: Cl/F of Itacitinib
timeFrame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
measure: Part 1: Response Rate at Months 3, 6, and 12
timeFrame: Months 3, 6, and 12
measure: Part 1 Expansion: Response Rate at Month 12
timeFrame: Month 12
measure: Part 1 Expansion: Time to Response
timeFrame: up to Month 12
measure: Part 1 Expansion: Duration of Response
timeFrame: up to 24 months
measure: Part 1 Expansion: Overall Survival
timeFrame: up to 36 months
measure: Part 1 Expansion: Nonrelapse Mortality (NRM) Rate
timeFrame: up to 24 months
measure: Part 1 Expansion: Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose at Day 180 From the Corticosteroid Dose on Day 1
timeFrame: Day 1; Day 180
measure: Part 1 Expansion: Percentage of Participants Successfully Tapered Off All Corticosteroids at Day 180
timeFrame: Day 180
measure: Part 1 Expansion: Relapse Rate of Malignant and Nonmalignant Hematologic Diseases
timeFrame: up to 1073 days
measure: Part 1 Expansion: Time to Primary Hematologic Disease Relapse
timeFrame: up to 24 months
measure: Part 2: Change From Baseline in Lee cGVHD Symptom Scale (LLS) Scores
timeFrame: Baseline; End of Treatment in Phase 2
measure: Part 2: Change From Baseline in Quality of Life-Short Form-36 Version 2 (QOL-SF-36 v2) Scores
timeFrame: Baseline; End of Treatment in Phase 2
measure: Part 2: Change From Baseline in EQ-5D-3L Scores
timeFrame: Baseline; End of Treatment in Phase 2
measure: Part 2: Change From Baseline in Patient Global Impression of Change (PGIC) Responses
timeFrame: Baseline; End of Treatment in Phase 2
measure: Part 2: Change From Baseline in Patient Global Impression of Severity (PGIS) Responses
timeFrame: Baseline; End of Treatment in Phase 2
measure: Part 2: Response Rate at Months 3 and 12
timeFrame: Months 3 and 12
measure: Part 2: Duration of Response
timeFrame: up to 24 months
measure: Part 2: Overall Survival
timeFrame: up to 36 months
measure: Part 2: NRM Rate
timeFrame: up to 24 months
measure: Part 2: Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose at Day 180 From the Corticosteroid Dose on Day 1
timeFrame: Day 1; Day 180
measure: Part 2: Percentage of Participants Successfully Tapered Off All Corticosteroids at Day 180
timeFrame: Day 180
measure: Part 2: Relapse Rate of Malignant and Nonmalignant Hematologic Diseases
timeFrame: up to 24 months
measure: Part 2: Time to Primary Hematologic Disease Relapse
timeFrame: up to 24 months
measure: Part 2: Number of Participants With Any TEAE
timeFrame: up to 30 days after the last dose in Phase 2
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center - Out Pt.
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas For Medical Sciences - Winthrop P Rockefeller Cancer Institute
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego Medical Center, Moores Cancer Center
state: California
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Augusta
country: United States
facility: Augusta University - Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital - Oncology Specislists Sc
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Hospital Authority
state: Kansas
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland - Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota, Masonic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester, James P. Wilmot Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson University Hospitals
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: Tri Star Bone Marrow Transplant
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: St David'S South Austin Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Sammons Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Linz
country: Austria
facility: Ordensklinikum Linz Gmbh Elisabethinen
city: Antwerpen
country: Belgium
facility: Zna Stuivenberg
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (Uza)
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven - Gasthuisberg
city: Liege
country: Belgium
facility: CENTRE HOSPITALIER UNIVERSITAIRE DE LIï¿½GE - SART TILMAN
city: Roeselare
country: Belgium
facility: AZ DELTA
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Hospital Maisonneuve Rosemont
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatchewan Cancer
state: Saskatchewan
city: Copenhagen
country: Denmark
facility: The Finsen Centre National Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Amiens
country: France
facility: Chu Amiens Picardie - Hopital Sud
city: Angers
country: France
facility: Centre Hospitalier D'Angers
city: Grenoble Cedex
country: France
facility: Chu de Grenoble - Hopital Albert Michallon
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
city: Nice
country: France
facility: Chu de Nice - Hospital L Archet
city: Rennes
country: France
facility: Chu de Rennes - Hospital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Tours
country: France
facility: Chru Hopitaux de Tours Hospital Bretonneau
city: Vandoeuvre Les Nancy
country: France
facility: Hopitaux de Brabois
city: Berlin
country: Germany
facility: Charite Berlin
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn Aoer
city: Dresden
country: Germany
facility: University Clinic Carl Gustav Carus Technical University Dresden
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen - Medizinische Klinik 5
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Halle
country: Germany
facility: UNIVERSITï¿½TSKLINIKUM HALLE (SAALE)
city: Hamburg
country: Germany
facility: University Medical Centre Hamburg-Eppendorf Centre of Oncology
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Koeln
country: Germany
facility: Universitatsklinikum Koln
city: Leipzig
country: Germany
facility: Selbststandige Abteilung Fur Hamatologie Und Internistische Onkologie
city: Mainz
country: Germany
facility: Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
city: Mannheim
country: Germany
facility: University Hospital Mannheim
city: Muenster
country: Germany
facility: Universitatsklinikum Munster
city: Munich
country: Germany
facility: Iii Medizinische Klinik Und Poliklinik Klinikum Rechts Der Isar Technische Universitat Munchen
city: Rostock
country: Germany
facility: Universitaetsmedizin Rostock
city: Tubingen
country: Germany
facility: Universitaetsklinikum in Tubingen
city: Chaidari
country: Greece
facility: University Hospital of West Attica - Attikon
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki G. Papanikolaou
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Medical Center Ein Karem Hadassah
city: Petach Tiqwa
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
city: Tel Aviv-yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Ancona
country: Italy
facility: CLINICA DI EMATOLOGIA, UNIVERSITï¿½ POLITECNICA DELLE MARCHE
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni Xxiii
city: Bologna
country: Italy
facility: L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA ï¿½ MALPIGHI
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
city: Catania
country: Italy
facility: Azienda Policlinico Vittorio Emanuele
city: Milano
country: Italy
facility: Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
city: Milan
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore
city: Modena
country: Italy
facility: A.O.U. Di Modena - Policlinico
city: Napoli
country: Italy
facility: A.O.U. Federico Ii
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello"
city: Pavia
country: Italy
facility: Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti
city: Roma
country: Italy
facility: Universita Degli Studi Di Roma La Sapienza - Umberto I Policlinico Di Roma - Centro Di Ematologia
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
city: Rozzano
country: Italy
facility: Irrcs Instituto Clinico Humanitas
city: San Giovanni Rotondo
country: Italy
facility: I.R.C.C.S. Casa Sollievo Della Sofferenza
city: Torino
country: Italy
facility: Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria Santa Maria Della Misericordia
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona (Crc)
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Oddzial W Gliwi
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego
city: Warszawa
country: Poland
facility: Mtz Clinical Research Sp. Zo.O.
city: Badalona
country: Spain
facility: Institut Catala D Oncologia
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: L'hospitalet de Llobregat
country: Spain
facility: Ico Institut Catala D Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Palma
country: Spain
facility: Son Espases University Hospital
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra (Cun)
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico de Santiago de Compostela
city: Valencia
country: Spain
facility: Hospital Universitario Y Politcnico de La Fe
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Huddinge
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Lund
country: Sweden
facility: Skane University Hospital Lund
city: Zurich
country: Switzerland
facility: Universitatsspital Zurich
city: Bristol
country: United Kingdom
facility: Bristol Haematology & Oncology Centre
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: Barts Health Nhs Trust - St Bartholomews Hospital
city: London
country: United Kingdom
facility: King'S College Hospital (Nhs Foundation)
city: London
country: United Kingdom
facility: Imperial College Healthcare Nhs Trust - Hammersmith Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals Nhs Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden Nhs Foundation Trust - Sutton
city: Tooting
country: United Kingdom
facility: St. George'S University Hospitals Nhs Foundation Trust
Study officials:
affiliation: Incyte Corporation
name: Rodica Morariu-Zamfir, MD
role: STUDY_DIRECTOR
References: