GRAVITAS-301: A Study of Itacitinib or Placebo in Combination With Corticosteroids for Treatment of Acute Graft-Versus-Host Disease
- Conditions
- Graft-versus-host Disease (GVHD)
- Interventions
- Registration Number
- NCT03139604
- Lead Sponsor
- Incyte Corporation
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 439
- 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.
-
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.
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Currently breast feeding.
-
Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
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Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment.
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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.
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Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Itacitinib Prednisone Itacitinib plus corticosteroids Placebo Methylprednisolone Matching placebo plus corticosteroids Itacitinib Methylprednisolone Itacitinib plus corticosteroids Placebo Placebo Matching placebo plus corticosteroids Itacitinib Itacitinib Itacitinib plus corticosteroids Placebo Prednisone Matching placebo plus corticosteroids
- Primary Outcome Measures
Name Time Method Overall Response Rate Based on Center for International Blood and Marrow Transplant Research (CIBMTR) Response Index Day 28 Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
- Secondary Outcome Measures
Name Time Method Nonrelapse Mortality Month 6,9,12 and 24 Defined as the percentage of participants who died due to causes other than malignancy relapse.
Duration of Response Baseline through 30-35 days after end of treatment, total particpation expected to average 24 months Defined as the interval from first response until GVHD progression or death.
Cmax of Itacitinib When Administered in Combination With Corticosteroids Protocol-defined timepoints up to Day 28 Defined as maximum observed plasma concentration.
Cmin of Itacitinib When Administered in Combination With Corticosteroids Protocol-defined timepoints up to Day 28 Defined as minimum observed plasma concentration.
Tmax of Itacitinib When Administered in Combination With Corticosteroids Protocol-defined timepoints up to Day 28 Defined as time to maximum plasma concentration.
AUC of Itacitinib When Administered in Combination With Corticosteroids Protocol-defined timepoints up to Day 28 Defined as area under the concentration-time curve.
CL/F of Itacitinib When Administered in Combination With Corticosteroids Protocol-defined timepoints up to Day 28 Defined as oral dose clearance.
Time to Response End of Study, total particpation expected to average 24 months Defined as the interval from treatment initiation to first response
Relapse Rate of Malignant and Nonmalignant Hematologic Disease Randomization through end of Study, study duration expected to average 24 months Defined as the proportion of subjects whose underlying hematologic disease relapses
Malignancy Relapse-related Mortality Rate Randomization through end of Study, study duration expected to average 24 months Defined as the proportion of subjects whose malignancy relapses and has a fatal outcome.
Failure-free Survival 6 months from randomization 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)
Overall Survival (OS) End of Study up to approximately 24 months Defined as the interval from study enrollment to death due to any cause.
Number of Treatment-emergent Adverse Events With INCB39110 30-35 days after end of treatment, approximately 24 months Adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment
Incidence Rate of Secondary Graft Failure Randomization through end of Study, study duration expected to average 24 months 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
Proportion of Subjects Who Discontinue Corticosteroids Days 28, 56, 100, and 180 Average and cumulative corticosteroid dose usage will be calculated and proportion of subjects discontinuing corticosteroids will be tabulated
Proportion of Subjects Who Discontinue Immunosuppressive Medications Days 56 and 100 Summary statistics of subjects discontinuing immunosuppressive medications will be calculated
Incidence Rate of aGVHD Flares up to day 100 Incidence Rate of cGVHD Days 180 and 365 Objective Response Rate Days 14, 56 and 100
Trial Locations
- Locations (129)
University of Southern California
🇺🇸Los Angeles, California, United States
University of California, Los Angeles (UCLA) - Medical Center
🇺🇸Los Angeles, California, United States
Advocate Lutheran General Hospital - Oncology Specialists SC
🇺🇸Park Ridge, Illinois, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Indiana University (IU) Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Indiana Blood and Marrow Transplant
🇺🇸Indianapolis, Indiana, United States
Hopital universitaire du Sart Tilman de Liege
🇧🇪Liege 1, Belgium
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
China Medical University Hospital
🇨🇳Taichung, Taiwan
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Austria
Centro Hospitalar Lisboa Norte - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Institut Jules Bordet
🇧🇪Brussels, Belgium
Oncology Hematology in Cincinnati
🇺🇸Cincinnati, Ohio, United States
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Centrum Onkologii- Instytut w Gliwicach
🇵🇱Gliwice, Poland
General Hospital of Thessaloniki G. Papanikolaou - Hematology Department
🇬🇷Chortiátis, Greece
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
University Clinic Carl Gustav Carus, Technical University Dresden
🇩🇪Dresden, Germany
UHKT Prague - Institute of Hematology and Blood Transfusion
🇨🇿Praha 2, Czechia
CHU Amiens Picardie - Hopital Sud
🇫🇷Amiens, France
Universitaetsmedizin der Johannes Gutenberg
🇩🇪Mainz, Germany
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
🇵🇹Porto, Portugal
Universitatsklinikum Freiburg - Klinik fur Innere Medizin I
🇩🇪Freiburg, Germany
Hopital de Hautepierre
🇫🇷Strasbourg cedex, France
Instituto Portugues de Oncologia de Lisboa Francisco Gentil EPE (IPO-Lisboa)
🇵🇹Lisboa, Portugal
Klinika Transplantacji Komorek Krwiotworczych - Instytut Hematologii i Transfuzjologii
🇵🇱Warsaw, Poland
Auckland District Health Board
🇳🇿Auckland, New Zealand
CHU de Nancy
🇫🇷Vandoeuvre les Nancy, France
Universitatsklinikum Hamburg - Eppendorf
🇩🇪Hamburg, Germany
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Hospital Universitario de Donostia
🇪🇸San Sebastián, Spain
Universtity Hospital Basel - Haematology
🇨🇭Basel, Switzerland
Universitaetsspital Zuerich - Klinik fuer Haematology
🇨🇭Zuerich, Switzerland
Hospital de la Santa Creu i Sant Pau - Servei de Hematologia Clinica
🇪🇸Barcelona, Spain
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Hopitaux Universitaires de Geneve
🇨🇭Geneve, Switzerland
Nottingham University Hospitals
🇬🇧Nottingham, United Kingdom
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Madrid, Spain
University of Oklahoma - Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute, LLC (SCRI)
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Hotel Dieu Hospital - Hematologie
🇫🇷Nantes, France
Hopital Haut Leveque - CHU Bordeaux - Maladies du sang
🇫🇷Pessac, France
Institut Claudius Regaud-Universitaire du Cancer Toulouse Oncopol
🇫🇷Toulouse Cedex 9, France
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hadassah Hebrew University Medical Center Ein Karem
🇮🇱Jerusalem, Israel
IRCCS Ospedale San Raffaele
🇮🇹Milan, Italy
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of California, San Diego (UCSD) - Moores Cancer Center
🇺🇸La Jolla, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
University of Florida (UF) - Division of Hematology & Oncology
🇺🇸Gainesville, Florida, United States
University of Colorado - Aurora Cancer Center
🇺🇸Aurora, Colorado, United States
Florida Hospital Cancer Institute
🇺🇸Orlando, Florida, United States
University of Miami - Sylvester Cancer Center
🇺🇸Miami, Florida, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Tulane University Medical Center
🇺🇸New Orleans, Louisiana, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
John Theurer Cancer Center At Hackensack UMC
🇺🇸Hackensack, New Jersey, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Columbia University
🇺🇸New York, New York, United States
Northwell Health
🇺🇸Lake Success, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Wake Forest Baptist Medical Center - Wake Forest University School of Medicine
🇺🇸Winston-Salem, North Carolina, United States
The Ohio State University (OSU)
🇺🇸Columbus, Ohio, United States
Oregon Health & Science University (OHSU)
🇺🇸Portland, Oregon, United States
Greenville Health System
🇺🇸Greenville, South Carolina, United States
Methodist Healthcare Foundation
🇺🇸Memphis, Tennessee, United States
University of Virginia Medical Center
🇺🇸Charlottesville, Virginia, United States
General Hospital Sint-Jan Brugge-Oostend
🇧🇪Brugge, Belgium
St Vincents Hospital Sydney Limited
🇦🇺Darlinghurst, Australia
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
Universitair Ziekenhuis Gent (UZG)
🇧🇪Gent, Belgium
CHRU de Lille-Hopital Claude Huriez
🇫🇷LILLE Cedex, France
Hopital Saint Louis
🇫🇷Paris, France
Universitaet zu Koln - Universitaetsklinikum Koeln (Uniklinik Koeln)
🇩🇪Köln, Germany
UKGM Marburg Innere Medizin: Haematologie Onkolog
🇩🇪Marburg, Germany
Rambam Health Care Campus
🇮🇱Haifa, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
C.T.M.O. Ospedale Roberto Binaghi ATS Cagliari
🇮🇹Cagliari, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
🇮🇹Milan, Italy
Azienda Ospedaliero Universitaria (AOU) Policlinico - Vittorio Emanuele - Presidio Ospedaliero Ferrarotto Alessi
🇮🇹Catania, Italy
Azienda Ospedaliero Universitaria Careggi
🇮🇹Firenze, 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
Presidio Ospedaliero Pescara
🇮🇹Pescara, Italy
Fondazione IRCCS Policlinco San Matteo
🇮🇹Pavia, Italy
University of Rome La Sapienza
🇮🇹Roma, Italy
Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti
🇮🇹Reggio Calabria, Italy
Azienda Unità Sanitaria Locale di Reggio Emilia
🇮🇹Reggio Emilia, 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, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Spain
Instituto Catalan de Oncologia - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Clinico de Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hammersmith Hospital
🇬🇧London, United Kingdom
AZ Delta
🇧🇪Roeselare, Belgium
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States