Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03139604
Other study ID # INCB 39110-301
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date July 19, 2017
Est. completion date July 13, 2020

Study information

Verified date July 2021
Source Incyte Corporation
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate itacitinib or placebo in combination with corticosteroids as first-line treatment of participants with Grade II to IV acute graft-versus-host disease (aGVHD).


Recruitment information / eligibility

Status Completed
Enrollment 439
Est. completion date July 13, 2020
Est. primary completion date May 2, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Has undergone 1 allo-HSCT from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible. - Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen. - Evidence of myeloid engraftment. Use of growth factor supplementation is allowed. - Serum creatinine = 2.0 mg/dL or creatinine clearance = 40 mL/min measured or calculated by Cockroft Gault equation. - Willing to avoid pregnancy or fathering children. - Able to give written informed consent and comply with all study visits and procedures. - Able to swallow and retain oral medication. Exclusion Criteria: - Has received more than 1 allo-HSCT. - Has received more than 2 days of systemic corticosteroids for aGVHD. - Presence of GVHD overlap syndrome. - Presence of an active uncontrolled infection. - Known human immunodeficiency virus infection. - Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation. - Participants with evidence of relapsed primary disease, or participants who have been treated for relapse after the allo-HSCT was performed. - Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization. - Severe organ dysfunction unrelated to underlying GVHD, including: - Cholestatic disorders or unresolved veno-occlusive disease of the liver. - Clinically significant or uncontrolled cardiac disease. - Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen. - Currently breast feeding. - Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted. - Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment. - Any medical complications or conditions that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. - Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

Study Design


Intervention

Drug:
Itacitinib
Itacitinib at the protocol-defined dose administered orally once daily (QD) plus corticosteroids.
Placebo
Matching placebo tablets administered orally once daily (QD) plus corticosteroids.
Prednisone
Oral prednisone may be used to begin standard corticosteroid background treatment at the investigator's discretion, at a dose equivalent to methylprednisolone 2 mg/kg per day.
Methylprednisolone
Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose appropriate for the severity of disease as background treatment.

Locations

Country Name City State
Australia St Vincents Hospital Sydney Limited Darlinghurst
Austria Ordensklinikum Linz GmbH Elisabethinen Linz
Belgium ZNA Stuivenberg Antwerpen
Belgium General Hospital Sint-Jan Brugge-Oostend Brugge
Belgium Cliniques Universitaires Saint-Luc Brussels
Belgium Institut Jules Bordet Brussels
Belgium Universitair Ziekenhuis Gent (UZG) Gent
Belgium Jessa Ziekenhuis Hasselt
Belgium Hopital universitaire du Sart Tilman de Liege Liege 1
Belgium AZ Delta Roeselare
Czechia UHKT Prague - Institute of Hematology and Blood Transfusion Praha 2
Finland Helsinki University Central Hospital Helsinki
France CHU Amiens Picardie - Hopital Sud Amiens
France CHRU de Lille-Hopital Claude Huriez LILLE Cedex
France Hotel Dieu Hospital - Hematologie Nantes
France Hopital Saint Louis Paris
France Hopital Haut Leveque - CHU Bordeaux - Maladies du sang Pessac
France Hopital de Hautepierre Strasbourg cedex
France Institut Claudius Regaud-Universitaire du Cancer Toulouse Oncopol Toulouse Cedex 9
France CHU de Nancy Vandoeuvre les Nancy
Germany University Clinic Carl Gustav Carus, Technical University Dresden Dresden
Germany Universitatsklinikum Freiburg - Klinik fur Innere Medizin I Freiburg
Germany Universitatsklinikum Hamburg - Eppendorf Hamburg
Germany Universitaet zu Koln - Universitaetsklinikum Koeln (Uniklinik Koeln) Köln
Germany Universitaetsklinikum Leipzig Leipzig
Germany Universitaetsmedizin der Johannes Gutenberg Mainz
Germany UKGM Marburg Innere Medizin: Haematologie Onkolog Marburg
Greece General Hospital of Thessaloniki G. Papanikolaou - Hematology Department Chortiátis
Israel Rambam Health Care Campus Haifa
Israel Hadassah Hebrew University Medical Center Ein Karem Jerusalem
Israel Chaim Sheba Medical Center Ramat Gan
Israel Tel Aviv Sourasky Medical Center Tel Aviv
Italy Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII Bergamo
Italy C.T.M.O. Ospedale Roberto Binaghi ATS Cagliari Cagliari
Italy Azienda Ospedaliero Universitaria (AOU) Policlinico - Vittorio Emanuele - Presidio Ospedaliero Ferrarotto Alessi Catania
Italy Azienda Ospedaliero Universitaria Careggi Firenze
Italy Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano Milan
Italy IRCCS Ospedale San Raffaele Milan
Italy ASST Grande Ospedale Metropolitano Niguarda Milano
Italy Clinica Ematologica CTA, Ospedale "San Gerardo" di Monza Monza
Italy Casa di Cura La Maddalena Palermo
Italy Fondazione IRCCS Policlinco San Matteo Pavia
Italy Presidio Ospedaliero Pescara Pescara
Italy Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti Reggio Calabria
Italy Azienda Unità Sanitaria Locale di Reggio Emilia Reggio Emilia
Italy University of Rome La Sapienza Roma
Italy Istituto Clinico Humanitas Rozzano
Italy A.O.U. Città della Salute e della Scienza di Torino Torino
Italy SOC Clinica Ematologica, Azienda Ospediero-Universitaria di Udine Udine
Korea, Republic of Seoul National University Hospital Seoul
New Zealand Auckland District Health Board Auckland
Poland Centrum Onkologii- Instytut w Gliwicach Gliwice
Poland Klinika Transplantacji Komorek Krwiotworczych - Instytut Hematologii i Transfuzjologii Warsaw
Portugal Centro Hospitalar Lisboa Norte - Hospital de Santa Maria Lisboa
Portugal Instituto Portugues de Oncologia de Lisboa Francisco Gentil EPE (IPO-Lisboa) Lisboa
Portugal Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE Porto
Spain Hospital Clinic i Provincial de Barcelona Barcelona
Spain Hospital de la Santa Creu i Sant Pau - Servei de Hematologia Clinica Barcelona
Spain Hospital Universitario Vall d'Hebron Barcelona
Spain Instituto Catalan de Oncologia - Hospital Duran i Reynals Barcelona
Spain Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves Granada
Spain Hospital General Universitario Gregorio Maranon Madrid
Spain Hospital Universitario La Paz Madrid
Spain Hospital Universitario Puerta de Hierro Majadahonda Madrid
Spain Hospital Universitario Ramon y Cajal Madrid
Spain Hospital Universitario de Salamanca Salamanca
Spain Hospital Universitario de Donostia San Sebastián
Spain Hospital Universitario Marques de Valdecilla Santander
Spain Hospital Clinico de Santiago de Compostela Santiago de Compostela
Spain Hospital Universitario Virgen del Rocio Sevilla
Spain Hospital Clinico Universitario de Valencia Valencia
Spain Hospital Universitari i Politecnic La Fe Valencia
Switzerland Universtity Hospital Basel - Haematology Basel
Switzerland Hopitaux Universitaires de Geneve Geneve
Switzerland Universitaetsspital Zuerich - Klinik fuer Haematology Zuerich
Taiwan China Medical University Hospital Taichung
United Kingdom Addenbrooke's Hospital Cambridge
United Kingdom University Hospital of Wales Cardiff
United Kingdom Hammersmith Hospital London
United Kingdom Nottingham University Hospitals Nottingham
United States University of Michigan Ann Arbor Michigan
United States University of Colorado - Aurora Cancer Center Aurora Colorado
United States University of Maryland Medical Center Baltimore Maryland
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Dana Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States Tufts Medical Center Boston Massachusetts
United States Levine Cancer Institute Charlotte North Carolina
United States University of Virginia Medical Center Charlottesville Virginia
United States University of Chicago Chicago Illinois
United States University of Illinois at Chicago Chicago Illinois
United States Oncology Hematology in Cincinnati Cincinnati Ohio
United States University Hospitals Cleveland Medical Center Cleveland Ohio
United States The Ohio State University (OSU) Columbus Ohio
United States Henry Ford Hospital Detroit Michigan
United States University of Florida (UF) - Division of Hematology & Oncology Gainesville Florida
United States Spectrum Health Grand Rapids Michigan
United States Greenville Health System Greenville South Carolina
United States John Theurer Cancer Center At Hackensack UMC Hackensack New Jersey
United States Indiana Blood and Marrow Transplant Indianapolis Indiana
United States Indiana University (IU) Melvin and Bren Simon Cancer Center Indianapolis Indiana
United States University of Iowa Iowa City Iowa
United States University of Mississippi Medical Center Jackson Mississippi
United States University of California, San Diego (UCSD) - Moores Cancer Center La Jolla California
United States Northwell Health Lake Success New York
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States University of California, Los Angeles (UCLA) - Medical Center Los Angeles California
United States University of Southern California Los Angeles California
United States Methodist Healthcare Foundation Memphis Tennessee
United States University of Miami - Sylvester Cancer Center Miami Florida
United States Sarah Cannon Research Institute, LLC (SCRI) Nashville Tennessee
United States Vanderbilt University Medical Center Nashville Tennessee
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey
United States Tulane University Medical Center New Orleans Louisiana
United States Columbia University New York New York
United States Memorial Sloan Kettering Cancer Center New York New York
United States University of Oklahoma - Health Sciences Center Oklahoma City Oklahoma
United States University of Nebraska Medical Center Omaha Nebraska
United States Florida Hospital Cancer Institute Orlando Florida
United States Advocate Lutheran General Hospital - Oncology Specialists SC Park Ridge Illinois
United States Thomas Jefferson University Philadelphia Pennsylvania
United States University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center Pittsburgh Pennsylvania
United States Oregon Health & Science University (OHSU) Portland Oregon
United States Washington University School of Medicine Saint Louis Missouri
United States Texas Transplant Institute San Antonio Texas
United States Stanford Cancer Center Stanford California
United States Stony Brook University Medical Center Stony Brook New York
United States University of Kansas Cancer Center Westwood Kansas
United States Wake Forest Baptist Medical Center - Wake Forest University School of Medicine Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Czechia,  Finland,  France,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Portugal,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Response Rate Based on Center for International Blood and Marrow Transplant Research (CIBMTR) Response Index Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR). Day 28
Secondary Nonrelapse Mortality Defined as the percentage of participants who died due to causes other than malignancy relapse. Month 6,9,12 and 24
Secondary Duration of Response Defined as the interval from first response until GVHD progression or death. Baseline through 30-35 days after end of treatment, total particpation expected to average 24 months
Secondary Cmax of Itacitinib When Administered in Combination With Corticosteroids Defined as maximum observed plasma concentration. Protocol-defined timepoints up to Day 28
Secondary Cmin of Itacitinib When Administered in Combination With Corticosteroids Defined as minimum observed plasma concentration. Protocol-defined timepoints up to Day 28
Secondary Tmax of Itacitinib When Administered in Combination With Corticosteroids Defined as time to maximum plasma concentration. Protocol-defined timepoints up to Day 28
Secondary AUC of Itacitinib When Administered in Combination With Corticosteroids Defined as area under the concentration-time curve. Protocol-defined timepoints up to Day 28
Secondary CL/F of Itacitinib When Administered in Combination With Corticosteroids Defined as oral dose clearance. Protocol-defined timepoints up to Day 28
Secondary Time to Response Defined as the interval from treatment initiation to first response End of Study, total particpation expected to average 24 months
Secondary Relapse Rate of Malignant and Nonmalignant Hematologic Disease Defined as the proportion of subjects whose underlying hematologic disease relapses Randomization through end of Study, study duration expected to average 24 months
Secondary Malignancy Relapse-related Mortality Rate Defined as the proportion of subjects whose malignancy relapses and has a fatal outcome. Randomization through end of Study, study duration expected to average 24 months
Secondary Failure-free Survival Defined as the proportion of subjects who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD) 6 months from randomization
Secondary Overall Survival (OS) Defined as the interval from study enrollment to death due to any cause. End of Study up to approximately 24 months
Secondary Number of Treatment-emergent Adverse Events With INCB39110 Adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment 30-35 days after end of treatment, approximately 24 months
Secondary Incidence Rate of Secondary Graft Failure Defined as > 95% recipient cells any time after engraftment with no signs of relapse, OR retransplantation because of secondary neutropenia (< 0.5 × 109/L) and/or thrombocytopenia (< 20 × 109/L) within 2 months of transplantion Randomization through end of Study, study duration expected to average 24 months
Secondary Proportion of Subjects Who Discontinue Corticosteroids Average and cumulative corticosteroid dose usage will be calculated and proportion of subjects discontinuing corticosteroids will be tabulated Days 28, 56, 100, and 180
Secondary Proportion of Subjects Who Discontinue Immunosuppressive Medications Summary statistics of subjects discontinuing immunosuppressive medications will be calculated Days 56 and 100
Secondary Incidence Rate of aGVHD Flares up to day 100
Secondary Incidence Rate of cGVHD Days 180 and 365
Secondary Objective Response Rate Days 14, 56 and 100
See also
  Status Clinical Trial Phase
Completed NCT03112603 - A Study of Ruxolitinib vs Best Available Therapy (BAT) in Patients With Steroid-refractory Chronic Graft vs. Host Disease (GvHD) After Bone Marrow Transplantation (REACH3) Phase 3
Completed NCT02953678 - A Study of Ruxolitinib in Combination With Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (REACH-1) Phase 2
Completed NCT02614612 - Study of Itacitinib in Combination With Corticosteroids for the Treatment of Acute GVHD Phase 1
Approved for marketing NCT05722912 - Expanded Access of Ruxolitinib Cream to Treat a Single Patient With cGVHD
Approved for marketing NCT03147742 - An Expanded Access Program of Ruxolitinib for the Treatment of Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplant