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Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Participants With New Onset Chronic Graft Versus Host Disease (cGVHD) (iNTEGRATE)

Primary Purpose

Chronic Graft Versus Host Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ibrutinib
Placebo
Prednisone
Sponsored by
Pharmacyclics LLC.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Graft Versus Host Disease focused on measuring 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

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Arizona Oncology - Scottsdale - Cancer Transplant Institute Location /ID# 1140-1120
  • LPCH Stanford /ID# 1140-1128
  • Ucsf /Id# 1140-0003
  • Stanford University/Stanford Cancer Center, Pasteur Drive /ID# 1140-0400
  • UCHSC Anschultz Cancer Pavilion /ID# 1140-0068
  • Children's National Medical Center /ID# 1140-1122
  • Jackson Memorial Hospital, University of Miami /ID# 1140-0647
  • Florida Hospital Cancer Institute/Adventist Health System/Sunbelt, Inc /ID# 1140-1121
  • Emory University, Winship Cancer Institute /ID# 1140-0033
  • Emory University/Winship Cancer Institute /ID# 1140-1179
  • University of Chicago /ID# 1140-0126
  • Loyola University /ID# 1140-0713
  • Indiana University Melvin and Bren Simon Cancer Center /ID# 1140-0010
  • University of Kentucky /ID# 1140-1140
  • University of Louisville Hospital /ID# 1140-1131
  • University of Maryland /ID# 1140-0205
  • Massachusetts General Hospital Cancer Center /ID# 1140-0020
  • Boston Childrens Hospital /ID# 1140-1615
  • Dana-Farber Cancer Institute /ID# 1140-0349
  • Barbara Ann Karmanos Cancer In /ID# 1140-0130
  • University of Minnesota /ID# 1140-0807
  • Mayo Clinic, Rochester, MN /ID# 1140-0240
  • Hackensack University Medical Center/ John Theurer Cancer Center /ID# 1140-0343
  • Rutgers Cancer Institute of NJ /ID# 1140-0803
  • Montefiore Medical Center - Moses Campus /ID# 1140-0120
  • New York Presbyterian Hospital/Weill Cornell Med College /ID# 1140-0200
  • Stony Brook University Medical Center /ID# 1140-0719
  • Columbia University Medical Center, MS-CHONY /ID# 1140-1124
  • Weill Cornell Physicians - Hematologic Malignancies & Bone Marrow Transplant /ID# 1140-0019
  • University of Rochester Cancer Center /ID# 1140-0127
  • University of North Carolina - Lineberger Comprehensive Cancer Center /ID# 1140-1133
  • Univ Hosp Cleveland /ID# 1140-0941
  • University of Pittsburgh - UPMC (Hillman Cancer Center) /ID# 1140-0050
  • Medical University of South Carolina, MUSC /ID# 1140-0738
  • Vanderbilt University Medical Center Vanderbilt Ingram Cancer Center /ID# 1140-0024
  • Methodist San Antonio /ID# 1140-1118
  • Fred Hutchinson Cancer Research Center /ID# 1140-0404
  • West Virginia University /ID# 1140-1090
  • The Kinghorn Cancer Centre /ID# 1140-1165
  • Westmead Hospital /ID# 1140-0848
  • Royal Brisbane and Women's Hospital /ID# 1140-0190
  • Royal Children's Hospital/ID# 1140-1154
  • Royal Melbourne Hospital (RMH) /ID# 1140-0633
  • Fiona Stanley Hospital /ID# 1140-0880
  • Univ. Klinik for Innere Medizin, Klinische Abteilung for Hematologie, Graz /ID# 1140-0373
  • Krankenhaus der Elisabethinen Linz /ID# 1140-0849
  • University of British Columbia (UBC) - Vancouver General Hospital (VGH) /ID# 1140-1166
  • The Ottawa Hospital Regional Cancer Center /ID# 1140-0159
  • Princess Margaret Cancer Centre /ID# 1140-0043
  • CHU Sainte-Justine /ID# 1140-1143
  • The First Affiliated Hospital of Soochow University /ID# 1140-1208
  • Chinese PLA General Hospital /ID# 1140-1198
  • Nanfang Hospital /ID# 1140-1379
  • UHC Zagreb /ID# 1140-1169
  • Hopital Saint-Louis - Institut Hematologie Centre Hayem CHU /ID# 1140-0735
  • Hopital de Brabois /ID# 1140-0775
  • CHU Amiens Groupe hospitalier Sud /ID# 1140-1205
  • CHU de GRENOBLE Alpes /ID# 1140-1058
  • Centre Hospitalier Regional Universitaire de Lille /ID# 1140-0750
  • CHU de Nantes /ID# 1140-0520
  • Groupe Hospitalier Pitie-Salpetriere /ID# 1140-0918
  • Robert Bosch Hospital /ID# 1140-1160
  • Universitatsklinikum Munster /ID# 1140-1195
  • Universitaetsklinikum Dresden /ID# 1140-1367
  • Hannover Medical School /ID# 1140-1141
  • Dr. Haunerschen Kinderspital /ID# 1140-1142
  • University Hospital of Regensburg /ID# 1140-1446
  • St. Laszlo Hospital /ID# 1140-1164
  • IRCCS Ospedale Pediatrico Bambino Gesu /ID# 1140-1150
  • A.O. Univ. Ospedali Riuniti /ID# 1140-0932
  • ASST Papa Giovanni XXIII /ID# 1140-1231
  • Ospedale San Raffaele IRCCS /ID# 1140-0523
  • University of Torino /ID# 1140-1268
  • Centro Trapianti Cellule Staminali, Ospedale Infantile Regina Margherita /ID# 1140-1156
  • Anjou Kousei Hospital /ID# 1140-1435
  • Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital /ID# 1140-1437
  • Kobe City Medical Center General Hospital /ID# 1140-1438
  • Hyogo College of Medicine College Hospital /Id# 1140-1434
  • Duplicate_University of Tsukuba Hospital /ID# 1140-1445
  • Tokai University Hospital /ID# 1140-1444
  • Duplicate_Kurashiki Central Hospital /ID# 1140-1442
  • Okayama University Hospital /ID# 1140-1430
  • Osaka Women's and Children's Hospital /ID# 1140-1440
  • Osaka City University Hospital /ID# 1140-1157
  • Dup_Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 1140-1439
  • National Center for Child Health and Development /ID# 1140-1443
  • Kumamoto Medical Center /ID# 1140-1431
  • Hokkaido University Hospital /ID# 1140-1436
  • Kyungpook National Univ Hosp /ID# 1140-1153
  • Yonsei University Health System, Severance Hospital /ID# 1140-0927
  • Samsung Medical Center /ID# 1140-0925
  • Cath Univ Seoul St Mary's Hosp /ID# 1140-0928
  • SoonChunHyang University Seoul /ID# 1140-1163
  • Asan Medical Center /ID# 1140-0963
  • National University Cancer Institute - National University Health System /ID# 1140-1155
  • Singapore General Hospital /ID# 1140-1162
  • Hospital Clinic /ID# 1140-0533
  • Hospital Santa Creu i Sant Pau /ID# 1140-0535
  • Hospital Universitario Virgen del Rocio /ID# 1140-0863
  • Hospital Clinico Universitario de Valencia /ID# 1140-1145
  • China Medical University Hosp /ID# 1140-1199
  • National Taiwan Univ Hosp /ID# 1140-1184

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ibrutinib + Prednisone

Placebo + Prednisone

Arm Description

Ibrutinib (420 mg) given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. The 420 mg dose was adjusted for cytochrome P450 [CYP] inhibitors or hepatic dysfunction as applicable. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses.

Placebo given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses.

Outcomes

Primary Outcome Measures

Primary Analysis: Response Rate at 48 Weeks
Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a complete response (CR) or a partial response (PR) at 48 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 48 weeks. Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Final Analysis: Response Rate at 48 Weeks
Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a complete response (CR) or a partial response (PR) at 48 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 48 weeks. Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.

Secondary Outcome Measures

Primary Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD
The cumulative incidence of withdrawal of all corticosteroids (95% confidence interval [CI]) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all corticosteroids at given time point. The time to withdrawal of corticosteroids is computed from randomization date to the first date of withdrawal of all corticosteroids for treatment of cGVHD to 0 mg daily for at least 30 days.
Final Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD
The cumulative incidence of withdrawal of all corticosteroids (95% confidence interval [CI]) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all corticosteroids at given time point. The time to withdrawal of corticosteroids is computed from randomization date to the first date of withdrawal of all corticosteroids for treatment of cGVHD to 0 mg daily for at least 30 days.
Primary Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants
The cumulative incidence of withdrawal of all immunosuppressants (95% CI) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all immunosuppressants at a given time point. The time to withdrawal of all immunosuppressants is computed from randomization date to the first date of withdrawal of all immunosuppressants for treatment of cGVHD, sustained for at least 30 days. All immunosuppressants include corticosteroids but they do not include ibrutinib.
Final Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants
The cumulative incidence of withdrawal of all immunosuppressants (95% CI) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all immunosuppressants at a given time point. The time to withdrawal of all immunosuppressants is computed from randomization date to the first date of withdrawal of all immunosuppressants for treatment of cGVHD, sustained for at least 30 days. All immunosuppressants include corticosteroids but they do not include ibrutinib.
Primary Analysis: Response Rate at 24 Weeks
Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a CR or PR at 24 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 24 weeks. Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Final Analysis: Response Rate at 24 Weeks
Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a CR or PR at 24 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 24 weeks. Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Primary Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits
Clinically meaningful improvement on Lee cGVHD symptom scale was defined as at least a 7-point decrease in Lee Symptom Scale overall summary score on at least 2 consecutive visits, not preceded by progressive disease, relapse of underlying disease or start of subsequent cGVHD treatment. The Lee cGVHD Symptom Scale score has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0- Not at all, 1- Slightly, 2 Moderately, 3 Quite a bit, 4-Extremely, with lower values representing a better outcome. A score is calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. An overall score is calculated as the average of these 7 subscales if at least 4 subscales have valid scores.
Final Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits
Clinically meaningful improvement on Lee cGVHD symptom scale was defined as at least a 7-point decrease in Lee Symptom Scale overall summary score on at least 2 consecutive visits, not preceded by progressive disease, relapse of underlying disease or start of subsequent cGVHD treatment. The Lee cGVHD Symptom Scale score has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0- Not at all, 1- Slightly, 2 Moderately, 3 Quite a bit, 4-Extremely, with lower values representing a better outcome. A score is calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. An overall score is calculated as the average of these 7 subscales if at least 4 subscales have valid scores.
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
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
Primary Analysis: Overall Survival (OS)
OS was defined as the time of randomization until the time of death due to any cause, in months.
Final Analysis: OS
OS was defined as the time of randomization until the time of death due to any cause, in months.
Primary Analysis: Duration of Response (DOR) for Participants Who Had PR or CR at Any Time
Response was defined using the NIH Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower GI, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR was defined as resolution of all manifestations in each organ or site. PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. Duration of response was estimated by Kaplan-Meier methodology.
Final Analysis: DOR for Participants Who Had PR or CR at Any Time
Response was defined using the NIH Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower GI, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR was defined as resolution of all manifestations in each organ or site. PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. Duration of response was estimated by Kaplan-Meier methodology.
Primary Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone
AE: any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity was graded according to the Common Terminology Criteria for Adverse Events version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death). Treatment-related events are those that were possibly related or related to study treatment per investigator's judgment. Treatment emergent AEs (TEAEs) occurred from the first dose of study drug up to 30 days after the last dose of study drug.
Final Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone
AE: any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity was graded according to the Common Terminology Criteria for Adverse Events version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death). Treatment-related events are those that were possibly related or related to study treatment per investigator's judgment. Treatment emergent AEs (TEAEs) occurred from the first dose of study drug up to 30 days after the last dose of study drug.

Full Information

First Posted
October 25, 2016
Last Updated
March 28, 2023
Sponsor
Pharmacyclics LLC.
Collaborators
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02959944
Brief Title
Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Participants With New Onset Chronic Graft Versus Host Disease (cGVHD)
Acronym
iNTEGRATE
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
May 11, 2017 (Actual)
Primary Completion Date
March 27, 2020 (Actual)
Study Completion Date
July 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
Collaborators
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
193 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ibrutinib + Prednisone
Arm Type
Experimental
Arm Description
Ibrutinib (420 mg) given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. The 420 mg dose was adjusted for cytochrome P450 [CYP] inhibitors or hepatic dysfunction as applicable. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses.
Arm Title
Placebo + Prednisone
Arm Type
Placebo Comparator
Arm Description
Placebo given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses.
Intervention Type
Drug
Intervention Name(s)
ibrutinib
Other Intervention Name(s)
IMBRUVICA®, PCI-32765
Intervention Description
Ibrutinib capsules administered orally daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules administered orally daily
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone administered daily
Primary Outcome Measure Information:
Title
Primary Analysis: Response Rate at 48 Weeks
Description
Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a complete response (CR) or a partial response (PR) at 48 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 48 weeks. Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Time Frame
48 weeks (Cumulatively up to 30 March 2020)
Title
Final Analysis: Response Rate at 48 Weeks
Description
Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a complete response (CR) or a partial response (PR) at 48 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 48 weeks. Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Time Frame
48 weeks (Cumulatively up to 12 July 2021)
Secondary Outcome Measure Information:
Title
Primary Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD
Description
The cumulative incidence of withdrawal of all corticosteroids (95% confidence interval [CI]) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all corticosteroids at given time point. The time to withdrawal of corticosteroids is computed from randomization date to the first date of withdrawal of all corticosteroids for treatment of cGVHD to 0 mg daily for at least 30 days.
Time Frame
Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 30 March 2020)
Title
Final Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD
Description
The cumulative incidence of withdrawal of all corticosteroids (95% confidence interval [CI]) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all corticosteroids at given time point. The time to withdrawal of corticosteroids is computed from randomization date to the first date of withdrawal of all corticosteroids for treatment of cGVHD to 0 mg daily for at least 30 days.
Time Frame
Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021)
Title
Primary Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants
Description
The cumulative incidence of withdrawal of all immunosuppressants (95% CI) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all immunosuppressants at a given time point. The time to withdrawal of all immunosuppressants is computed from randomization date to the first date of withdrawal of all immunosuppressants for treatment of cGVHD, sustained for at least 30 days. All immunosuppressants include corticosteroids but they do not include ibrutinib.
Time Frame
Months 3, 6, 9, 12, 15, 18, 21, 24 (cumulatively up to 30 March 2020)
Title
Final Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants
Description
The cumulative incidence of withdrawal of all immunosuppressants (95% CI) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all immunosuppressants at a given time point. The time to withdrawal of all immunosuppressants is computed from randomization date to the first date of withdrawal of all immunosuppressants for treatment of cGVHD, sustained for at least 30 days. All immunosuppressants include corticosteroids but they do not include ibrutinib.
Time Frame
Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021)
Title
Primary Analysis: Response Rate at 24 Weeks
Description
Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a CR or PR at 24 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 24 weeks. Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Time Frame
24 weeks (Cumulatively up to 30 March 2020)
Title
Final Analysis: Response Rate at 24 Weeks
Description
Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a CR or PR at 24 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 24 weeks. Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Time Frame
24 weeks (Cumulatively up to 12 July 2021)
Title
Primary Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits
Description
Clinically meaningful improvement on Lee cGVHD symptom scale was defined as at least a 7-point decrease in Lee Symptom Scale overall summary score on at least 2 consecutive visits, not preceded by progressive disease, relapse of underlying disease or start of subsequent cGVHD treatment. The Lee cGVHD Symptom Scale score has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0- Not at all, 1- Slightly, 2 Moderately, 3 Quite a bit, 4-Extremely, with lower values representing a better outcome. A score is calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. An overall score is calculated as the average of these 7 subscales if at least 4 subscales have valid scores.
Time Frame
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)
Title
Final Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits
Description
Clinically meaningful improvement on Lee cGVHD symptom scale was defined as at least a 7-point decrease in Lee Symptom Scale overall summary score on at least 2 consecutive visits, not preceded by progressive disease, relapse of underlying disease or start of subsequent cGVHD treatment. The Lee cGVHD Symptom Scale score has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0- Not at all, 1- Slightly, 2 Moderately, 3 Quite a bit, 4-Extremely, with lower values representing a better outcome. A score is calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. An overall score is calculated as the average of these 7 subscales if at least 4 subscales have valid scores.
Time Frame
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)
Title
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
Time Frame
24 weeks (Cumulatively up to 30 March 2020)
Title
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
Time Frame
24 weeks (Cumulatively up to 12 July 2021)
Title
Primary Analysis: Overall Survival (OS)
Description
OS was defined as the time of randomization until the time of death due to any cause, in months.
Time Frame
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.
Title
Final Analysis: OS
Description
OS was defined as the time of randomization until the time of death due to any cause, in months.
Time Frame
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.
Title
Primary Analysis: Duration of Response (DOR) for Participants Who Had PR or CR at Any Time
Description
Response was defined using the NIH Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower GI, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR was defined as resolution of all manifestations in each organ or site. PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. Duration of response was estimated by Kaplan-Meier methodology.
Time Frame
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)
Title
Final Analysis: DOR for Participants Who Had PR or CR at Any Time
Description
Response was defined using the NIH Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower GI, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR was defined as resolution of all manifestations in each organ or site. PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. Duration of response was estimated by Kaplan-Meier methodology.
Time Frame
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)
Title
Primary Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone
Description
AE: any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity was graded according to the Common Terminology Criteria for Adverse Events version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death). Treatment-related events are those that were possibly related or related to study treatment per investigator's judgment. Treatment emergent AEs (TEAEs) occurred from the first dose of study drug up to 30 days after the last dose of study drug.
Time Frame
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.
Title
Final Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone
Description
AE: any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity was graded according to the Common Terminology Criteria for Adverse Events version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death). Treatment-related events are those that were possibly related or related to study treatment per investigator's judgment. Treatment emergent AEs (TEAEs) occurred from the first dose of study drug up to 30 days after the last dose of study drug.
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Justin Wahlstrom, MD
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology - Scottsdale - Cancer Transplant Institute Location /ID# 1140-1120
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258-4547
Country
United States
Facility Name
LPCH Stanford /ID# 1140-1128
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Ucsf /Id# 1140-0003
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University/Stanford Cancer Center, Pasteur Drive /ID# 1140-0400
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
UCHSC Anschultz Cancer Pavilion /ID# 1140-0068
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
Facility Name
Children's National Medical Center /ID# 1140-1122
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Jackson Memorial Hospital, University of Miami /ID# 1140-0647
City
Miami
State/Province
Florida
ZIP/Postal Code
33136-1096
Country
United States
Facility Name
Florida Hospital Cancer Institute/Adventist Health System/Sunbelt, Inc /ID# 1140-1121
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Emory University, Winship Cancer Institute /ID# 1140-0033
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Emory University/Winship Cancer Institute /ID# 1140-1179
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago /ID# 1140-0126
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University /ID# 1140-0713
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Indiana University Melvin and Bren Simon Cancer Center /ID# 1140-0010
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5112
Country
United States
Facility Name
University of Kentucky /ID# 1140-1140
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40508-2678
Country
United States
Facility Name
University of Louisville Hospital /ID# 1140-1131
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Maryland /ID# 1140-0205
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center /ID# 1140-0020
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston Childrens Hospital /ID# 1140-1615
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute /ID# 1140-0349
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Barbara Ann Karmanos Cancer In /ID# 1140-0130
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Minnesota /ID# 1140-0807
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic, Rochester, MN /ID# 1140-0240
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Hackensack University Medical Center/ John Theurer Cancer Center /ID# 1140-0343
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Rutgers Cancer Institute of NJ /ID# 1140-0803
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Montefiore Medical Center - Moses Campus /ID# 1140-0120
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
New York Presbyterian Hospital/Weill Cornell Med College /ID# 1140-0200
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Stony Brook University Medical Center /ID# 1140-0719
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Columbia University Medical Center, MS-CHONY /ID# 1140-1124
City
New York
State/Province
New York
ZIP/Postal Code
10032-1559
Country
United States
Facility Name
Weill Cornell Physicians - Hematologic Malignancies & Bone Marrow Transplant /ID# 1140-0019
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester Cancer Center /ID# 1140-0127
City
Rochester
State/Province
New York
ZIP/Postal Code
14642-0001
Country
United States
Facility Name
University of North Carolina - Lineberger Comprehensive Cancer Center /ID# 1140-1133
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27516
Country
United States
Facility Name
Univ Hosp Cleveland /ID# 1140-0941
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
University of Pittsburgh - UPMC (Hillman Cancer Center) /ID# 1140-0050
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Medical University of South Carolina, MUSC /ID# 1140-0738
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Vanderbilt University Medical Center Vanderbilt Ingram Cancer Center /ID# 1140-0024
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-5280
Country
United States
Facility Name
Methodist San Antonio /ID# 1140-1118
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3710
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center /ID# 1140-0404
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
West Virginia University /ID# 1140-1090
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
The Kinghorn Cancer Centre /ID# 1140-1165
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Westmead Hospital /ID# 1140-0848
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital /ID# 1140-0190
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Royal Children's Hospital/ID# 1140-1154
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Royal Melbourne Hospital (RMH) /ID# 1140-0633
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Fiona Stanley Hospital /ID# 1140-0880
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Facility Name
Univ. Klinik for Innere Medizin, Klinische Abteilung for Hematologie, Graz /ID# 1140-0373
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Krankenhaus der Elisabethinen Linz /ID# 1140-0849
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
University of British Columbia (UBC) - Vancouver General Hospital (VGH) /ID# 1140-1166
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
The Ottawa Hospital Regional Cancer Center /ID# 1140-0159
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Princess Margaret Cancer Centre /ID# 1140-0043
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
CHU Sainte-Justine /ID# 1140-1143
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
The First Affiliated Hospital of Soochow University /ID# 1140-1208
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Facility Name
Chinese PLA General Hospital /ID# 1140-1198
City
Beijing
ZIP/Postal Code
100853
Country
China
Facility Name
Nanfang Hospital /ID# 1140-1379
City
Guangzhou Shi
ZIP/Postal Code
510000
Country
China
Facility Name
UHC Zagreb /ID# 1140-1169
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
Hopital Saint-Louis - Institut Hematologie Centre Hayem CHU /ID# 1140-0735
City
Paris
State/Province
Ile-de-France
ZIP/Postal Code
75010
Country
France
Facility Name
Hopital de Brabois /ID# 1140-0775
City
Vandoeuvre-lès-nancy
State/Province
Meurthe-et-Moselle
ZIP/Postal Code
54511
Country
France
Facility Name
CHU Amiens Groupe hospitalier Sud /ID# 1140-1205
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
CHU de GRENOBLE Alpes /ID# 1140-1058
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Centre Hospitalier Regional Universitaire de Lille /ID# 1140-0750
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CHU de Nantes /ID# 1140-0520
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Groupe Hospitalier Pitie-Salpetriere /ID# 1140-0918
City
Paris
ZIP/Postal Code
33000
Country
France
Facility Name
Robert Bosch Hospital /ID# 1140-1160
City
Stuttgart
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
70376
Country
Germany
Facility Name
Universitatsklinikum Munster /ID# 1140-1195
City
Munster
State/Province
Niedersachsen
ZIP/Postal Code
48149
Country
Germany
Facility Name
Universitaetsklinikum Dresden /ID# 1140-1367
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Hannover Medical School /ID# 1140-1141
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Dr. Haunerschen Kinderspital /ID# 1140-1142
City
Munich
ZIP/Postal Code
80337
Country
Germany
Facility Name
University Hospital of Regensburg /ID# 1140-1446
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
St. Laszlo Hospital /ID# 1140-1164
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
IRCCS Ospedale Pediatrico Bambino Gesu /ID# 1140-1150
City
Rome
State/Province
Lazio
ZIP/Postal Code
00165
Country
Italy
Facility Name
A.O. Univ. Ospedali Riuniti /ID# 1140-0932
City
Ancona
State/Province
Marche
ZIP/Postal Code
60126
Country
Italy
Facility Name
ASST Papa Giovanni XXIII /ID# 1140-1231
City
Bergamo
ZIP/Postal Code
24127
Country
Italy
Facility Name
Ospedale San Raffaele IRCCS /ID# 1140-0523
City
Milan
ZIP/Postal Code
20132
Country
Italy
Facility Name
University of Torino /ID# 1140-1268
City
Torino
ZIP/Postal Code
10124
Country
Italy
Facility Name
Centro Trapianti Cellule Staminali, Ospedale Infantile Regina Margherita /ID# 1140-1156
City
Turin
ZIP/Postal Code
10126
Country
Italy
Facility Name
Anjou Kousei Hospital /ID# 1140-1435
City
Anjo
State/Province
Aichi
ZIP/Postal Code
446-8602
Country
Japan
Facility Name
Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital /ID# 1140-1437
City
Hiroshima-shi
State/Province
Hiroshima
ZIP/Postal Code
730-8619
Country
Japan
Facility Name
Kobe City Medical Center General Hospital /ID# 1140-1438
City
Kobe-shi
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Hyogo College of Medicine College Hospital /Id# 1140-1434
City
Nishinomiya-shi
State/Province
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
Facility Name
Duplicate_University of Tsukuba Hospital /ID# 1140-1445
City
Tsukuba-shi
State/Province
Ibaraki
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Tokai University Hospital /ID# 1140-1444
City
Isehara-shi
State/Province
Kanagawa
ZIP/Postal Code
259-1193
Country
Japan
Facility Name
Duplicate_Kurashiki Central Hospital /ID# 1140-1442
City
Kurishiki-shi
State/Province
Okayama
ZIP/Postal Code
710-8602
Country
Japan
Facility Name
Okayama University Hospital /ID# 1140-1430
City
Okayama-shi
State/Province
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
Osaka Women's and Children's Hospital /ID# 1140-1440
City
Izumi-Shi
State/Province
Osaka
ZIP/Postal Code
594-1101
Country
Japan
Facility Name
Osaka City University Hospital /ID# 1140-1157
City
Osaka-shi
State/Province
Osaka
ZIP/Postal Code
545-8586
Country
Japan
Facility Name
Dup_Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 1140-1439
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8677
Country
Japan
Facility Name
National Center for Child Health and Development /ID# 1140-1443
City
Setagaya-ku
State/Province
Tokyo
ZIP/Postal Code
157-8535
Country
Japan
Facility Name
Kumamoto Medical Center /ID# 1140-1431
City
Kumamoto
ZIP/Postal Code
860-0008
Country
Japan
Facility Name
Hokkaido University Hospital /ID# 1140-1436
City
Sapporo
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Kyungpook National Univ Hosp /ID# 1140-1153
City
Daegu
State/Province
Daegu Gwang Yeogsi
ZIP/Postal Code
41944
Country
Korea, Republic of
Facility Name
Yonsei University Health System, Severance Hospital /ID# 1140-0927
City
Seodaemun-gu
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Samsung Medical Center /ID# 1140-0925
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Cath Univ Seoul St Mary's Hosp /ID# 1140-0928
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
SoonChunHyang University Seoul /ID# 1140-1163
City
Seoul
ZIP/Postal Code
04401
Country
Korea, Republic of
Facility Name
Asan Medical Center /ID# 1140-0963
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
National University Cancer Institute - National University Health System /ID# 1140-1155
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Facility Name
Singapore General Hospital /ID# 1140-1162
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Hospital Clinic /ID# 1140-0533
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Santa Creu i Sant Pau /ID# 1140-0535
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio /ID# 1140-0863
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia /ID# 1140-1145
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
China Medical University Hosp /ID# 1140-1199
City
Taichung City
State/Province
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
National Taiwan Univ Hosp /ID# 1140-1184
City
Taipei City
State/Province
Taipei
ZIP/Postal Code
10002
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.
IPD Sharing URL
http://yoda.yale.edu

Learn more about this trial

Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Participants With New Onset Chronic Graft Versus Host Disease (cGVHD)

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