Clinical trial NCT02959944: Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Participants With New Onset Chronic Graft Versus Host Disease (cGVHD)
Official title: A Randomized, Double-Blind Phase 3 Study of Ibrutinib in Combination With Corticosteroids Versus Placebo in Combination With Corticosteroids in Subjects With New Onset Chronic Graft Versus Host Disease (cGVHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Graft Versus Host Disease
Keywords: chronic graft versus host disease
PCYC1140
PCYC1140IM
1140
Ibrutinib
GVHD
Steroid dependent
refractory
chronic
PCI32765
IMBRUVICA
Pharmacyclics
PCYC
graft versus host disease
immunology
new onset graft versus host disease
INTEGRATE
Corticosteroids
prednisone
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2016-11-09
Enrollment: 193
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of ibrutinib in combination with prednisone in subjects with newly diagnosed moderate to severe cGVHD.


Eligibility criteria: Key Inclusion Criteria:

* New onset moderate or severe cGVHD as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project Criteria
* Need for systemic treatment with corticosteroids for cGVHD
* No previous systemic treatment for cGVHD (including extracorporeal photopheresis \[ECP\])
* Participants may be receiving other immunosuppressants for the prophylaxis or treatment of acute GVHD but if the subject is receiving prednisone for prophylaxis or treatment of acute GVHD it must be at or below 0.5 mg/kg/d
* Age ≥12 years old
* Karnofsky or Lansky (subjects \<16 years) performance status ≥60

Key Exclusion Criteria:

* Received any previous systemic treatment for cGVHD with the exception of corticosteroids administered for cGVHD within the 72 hours prior to signing the informed consent form.
* Inability to begin a prednisone dose ≥0.5 mg/kg/d for the treatment of cGVHD
* Any uncontrolled infection or active infection requiring ongoing systemic treatment
* Progressive underlying malignant disease or any post-transplant lymphoproliferative disease
* Known bleeding disorders
* Active hepatitis C virus (HCV) or hepatitis B virus (HBV)

Primary outcomes:
measure: Primary Analysis: Response Rate at 48 Weeks
timeFrame: 48 weeks (Cumulatively up to 30 March 2020)
measure: Final Analysis: Response Rate at 48 Weeks
timeFrame: 48 weeks (Cumulatively up to 12 July 2021)
Secondary outcomes:
measure: Primary Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD
timeFrame: Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 30 March 2020)
measure: Final Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD
timeFrame: Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021)
measure: Primary Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants
timeFrame: Months 3, 6, 9, 12, 15, 18, 21, 24 (cumulatively up to 30 March 2020)
measure: Final Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants
timeFrame: Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021)
measure: Primary Analysis: Response Rate at 24 Weeks
timeFrame: 24 weeks (Cumulatively up to 30 March 2020)
measure: Final Analysis: Response Rate at 24 Weeks
timeFrame: 24 weeks (Cumulatively up to 12 July 2021)
measure: Primary Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits
timeFrame: Assessed at Weeks 5, 13, 25, 37, 49, 30 days after the last dose of study drug, and then every 12 weeks of follow-up until progressed disease. (Cumulatively up to 30 March 2020)
measure: Final Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits
timeFrame: Assessed at Weeks 5, 13, 25, 37, 49, 30 days after the last dose of study drug, and then every 12 weeks of follow-up until progressed disease. (Cumulatively up to 12 July 2021)
measure: Primary Analysis: Percentage of Participants Who Achieved Reduction of Prednisone Dose Level to Less Than 0.15 mg/kg/Day at 24 Weeks Sustained for at Least 30 Days
timeFrame: 24 weeks (Cumulatively up to 30 March 2020)
measure: Final Analysis: Percentage of Participants Who Achieved Reduction of Prednisone Dose Level to Less Than 0.15 mg/kg/Day at 24 Weeks Sustained for at Least 30 Days
timeFrame: 24 weeks (Cumulatively up to 12 July 2021)
measure: Primary Analysis: Overall Survival (OS)
timeFrame: Median time on study (cumulatively up to 30 March 2020) was 19.8 months and 18.4 months for the Ibrutinib + Prednisone and Placebo + Prednisone arms, respectively.
measure: Final Analysis: OS
timeFrame: Median time on study (cumulatively up to 12 July 2021) was 33.1 months and 32.5 months for the Ibrutinib + Prednisone and Placebo + Prednisone arms, respectively.
measure: Primary Analysis: Duration of Response (DOR) for Participants Who Had PR or CR at Any Time
timeFrame: Response was assessed every 4 weeks from Week 5 through Week 25, Week 37, Week 49, 30 days after the last dose of study drug, and then every 12 weeks of follow-up until progressed disease. (Cumulatively up to 30 March 2020)
measure: Final Analysis: DOR for Participants Who Had PR or CR at Any Time
timeFrame: Response was assessed every 4 weeks from Week 5 through Week 25, Week 37, Week 49, 30 days after the last dose of study drug, and then every 12 weeks of follow-up until progressed disease. (Cumulatively up to 12 July 2021)
measure: Primary Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone
timeFrame: From first dose of study drug through the end of treatment plus 30 days. As of data cutoff (cumulatively up to 30 March 2020), median ibrutinib treatment duration was 5.4 months and the median placebo treatment duration was 6.4 months.
measure: Final Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone
timeFrame: From first dose of study drug through the end of treatment plus 30 days. As of data cutoff (cumulatively up to 12 July 2021), median ibrutinib treatment duration was 5.4 months and the median placebo treatment duration was 6.4 months.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Arizona Oncology - Scottsdale - Cancer Transplant Institute Location /ID# 1140-1120
state: Arizona
city: Palo Alto
country: United States
facility: LPCH Stanford /ID# 1140-1128
state: California
city: San Francisco
country: United States
facility: Ucsf /Id# 1140-0003
state: California
city: Stanford
country: United States
facility: Stanford University/Stanford Cancer Center, Pasteur Drive /ID# 1140-0400
state: California
city: Aurora
country: United States
facility: UCHSC Anschultz Cancer Pavilion /ID# 1140-0068
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center /ID# 1140-1122
state: District of Columbia
city: Miami
country: United States
facility: Jackson Memorial Hospital, University of Miami /ID# 1140-0647
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute/Adventist Health System/Sunbelt, Inc /ID# 1140-1121
state: Florida
city: Atlanta
country: United States
facility: Emory University, Winship Cancer Institute /ID# 1140-0033
state: Georgia
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute /ID# 1140-1179
state: Georgia
city: Chicago
country: United States
facility: University of Chicago /ID# 1140-0126
state: Illinois
city: Maywood
country: United States
facility: Loyola University /ID# 1140-0713
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center /ID# 1140-0010
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky /ID# 1140-1140
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Hospital /ID# 1140-1131
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland /ID# 1140-0205
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center /ID# 1140-0020
state: Massachusetts
city: Boston
country: United States
facility: Boston Childrens Hospital /ID# 1140-1615
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 1140-0349
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer In /ID# 1140-0130
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota /ID# 1140-0807
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic, Rochester, MN /ID# 1140-0240
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center/ John Theurer Cancer Center /ID# 1140-0343
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of NJ /ID# 1140-0803
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus /ID# 1140-0120
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Weill Cornell Med College /ID# 1140-0200
state: New York
city: New York
country: United States
facility: Stony Brook University Medical Center /ID# 1140-0719
state: New York
city: New York
country: United States
facility: Columbia University Medical Center, MS-CHONY /ID# 1140-1124
state: New York
city: New York
country: United States
facility: Weill Cornell Physicians - Hematologic Malignancies & Bone Marrow Transplant /ID# 1140-0019
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center /ID# 1140-0127
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Lineberger Comprehensive Cancer Center /ID# 1140-1133
state: North Carolina
city: Cleveland
country: United States
facility: Univ Hosp Cleveland /ID# 1140-0941
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh - UPMC (Hillman Cancer Center) /ID# 1140-0050
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, MUSC /ID# 1140-0738
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center Vanderbilt Ingram Cancer Center /ID# 1140-0024
state: Tennessee
city: San Antonio
country: United States
facility: Methodist San Antonio /ID# 1140-1118
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center /ID# 1140-0404
state: Washington
city: Morgantown
country: United States
facility: West Virginia University /ID# 1140-1090
state: West Virginia
city: Darlinghurst
country: Australia
facility: The Kinghorn Cancer Centre /ID# 1140-1165
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital /ID# 1140-0848
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital /ID# 1140-0190
state: Queensland
city: Parkville
country: Australia
facility: Royal Children's Hospital/ID# 1140-1154
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital (RMH) /ID# 1140-0633
state: Victoria
city: Perth
country: Australia
facility: Fiona Stanley Hospital /ID# 1140-0880
state: Western Australia
city: Graz
country: Austria
facility: Univ. Klinik for Innere Medizin, Klinische Abteilung for Hematologie, Graz /ID# 1140-0373
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz /ID# 1140-0849
city: Vancouver
country: Canada
facility: University of British Columbia (UBC) - Vancouver General Hospital (VGH) /ID# 1140-1166
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Regional Cancer Center /ID# 1140-0159
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre /ID# 1140-0043
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine /ID# 1140-1143
state: Quebec
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University /ID# 1140-1208
state: Jiangsu
city: Beijing
country: China
facility: Chinese PLA General Hospital /ID# 1140-1198
city: Guangzhou Shi
country: China
facility: Nanfang Hospital /ID# 1140-1379
city: Zagreb
country: Croatia
facility: UHC Zagreb /ID# 1140-1169
city: Paris
country: France
facility: Hopital Saint-Louis - Institut Hematologie Centre Hayem CHU /ID# 1140-0735
state: Ile-de-France
city: Vandoeuvre-lès-nancy
country: France
facility: Hopital de Brabois /ID# 1140-0775
state: Meurthe-et-Moselle
city: Amiens
country: France
facility: CHU Amiens Groupe hospitalier Sud /ID# 1140-1205
city: Grenoble
country: France
facility: CHU de GRENOBLE Alpes /ID# 1140-1058
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille /ID# 1140-0750
city: Nantes
country: France
facility: CHU de Nantes /ID# 1140-0520
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere /ID# 1140-0918
city: Stuttgart
country: Germany
facility: Robert Bosch Hospital /ID# 1140-1160
state: Baden-Wuerttemberg
city: Munster
country: Germany
facility: Universitatsklinikum Munster /ID# 1140-1195
state: Niedersachsen
city: Dresden
country: Germany
facility: Universitaetsklinikum Dresden /ID# 1140-1367
city: Hannover
country: Germany
facility: Hannover Medical School /ID# 1140-1141
city: Munich
country: Germany
facility: Dr. Haunerschen Kinderspital /ID# 1140-1142
city: Regensburg
country: Germany
facility: University Hospital of Regensburg /ID# 1140-1446
city: Budapest
country: Hungary
facility: St. Laszlo Hospital /ID# 1140-1164
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu /ID# 1140-1150
state: Lazio
city: Ancona
country: Italy
facility: A.O. Univ. Ospedali Riuniti /ID# 1140-0932
state: Marche
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII /ID# 1140-1231
city: Milan
country: Italy
facility: Ospedale San Raffaele IRCCS /ID# 1140-0523
city: Torino
country: Italy
facility: University of Torino /ID# 1140-1268
city: Turin
country: Italy
facility: Centro Trapianti Cellule Staminali, Ospedale Infantile Regina Margherita /ID# 1140-1156
city: Anjo
country: Japan
facility: Anjou Kousei Hospital /ID# 1140-1435
state: Aichi
city: Hiroshima-shi
country: Japan
facility: Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital /ID# 1140-1437
state: Hiroshima
city: Kobe-shi
country: Japan
facility: Kobe City Medical Center General Hospital /ID# 1140-1438
state: Hyogo
city: Nishinomiya-shi
country: Japan
facility: Hyogo College of Medicine College Hospital /Id# 1140-1434
state: Hyogo
city: Tsukuba-shi
country: Japan
facility: Duplicate_University of Tsukuba Hospital /ID# 1140-1445
state: Ibaraki
city: Isehara-shi
country: Japan
facility: Tokai University Hospital /ID# 1140-1444
state: Kanagawa
city: Kurishiki-shi
country: Japan
facility: Duplicate_Kurashiki Central Hospital /ID# 1140-1442
state: Okayama
city: Okayama-shi
country: Japan
facility: Okayama University Hospital /ID# 1140-1430
state: Okayama
city: Izumi-Shi
country: Japan
facility: Osaka Women's and Children's Hospital /ID# 1140-1440
state: Osaka
city: Osaka-shi
country: Japan
facility: Osaka City University Hospital /ID# 1140-1157
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Dup_Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 1140-1439
state: Tokyo
city: Setagaya-ku
country: Japan
facility: National Center for Child Health and Development /ID# 1140-1443
state: Tokyo
city: Kumamoto
country: Japan
facility: Kumamoto Medical Center /ID# 1140-1431
city: Sapporo
country: Japan
facility: Hokkaido University Hospital /ID# 1140-1436
city: Daegu
country: Korea, Republic of
facility: Kyungpook National Univ Hosp /ID# 1140-1153
state: Daegu Gwang Yeogsi
city: Seodaemun-gu
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital /ID# 1140-0927
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 1140-0925
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Cath Univ Seoul St Mary's Hosp /ID# 1140-0928
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: SoonChunHyang University Seoul /ID# 1140-1163
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 1140-0963
city: Singapore
country: Singapore
facility: National University Cancer Institute - National University Health System /ID# 1140-1155
city: Singapore
country: Singapore
facility: Singapore General Hospital /ID# 1140-1162
city: Barcelona
country: Spain
facility: Hospital Clinic /ID# 1140-0533
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau /ID# 1140-0535
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 1140-0863
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 1140-1145
city: Taichung City
country: Taiwan
facility: China Medical University Hosp /ID# 1140-1199
state: Taichung
city: Taipei City
country: Taiwan
facility: National Taiwan Univ Hosp /ID# 1140-1184
state: Taipei
Study officials:
affiliation: Pharmacyclics LLC.
name: Justin Wahlstrom, MD
role: STUDY_DIRECTOR
References: