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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02959944




Registration number
NCT02959944
Ethics application status
Date submitted
25/10/2016
Date registered
9/11/2016

Titles & IDs
Public title
Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Participants With New Onset Chronic Graft Versus Host Disease (cGVHD)
Scientific 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)
Secondary ID [1] 0 0
PCYC-1140-IM
Universal Trial Number (UTN)
Trial acronym
iNTEGRATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Graft Versus Host Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ibrutinib
Treatment: Drugs - Placebo
Treatment: Drugs - Prednisone

Experimental: Ibrutinib + Prednisone - 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 comparator: Placebo + Prednisone - 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.


Treatment: Drugs: ibrutinib
Ibrutinib capsules administered orally daily

Treatment: Drugs: Placebo
Placebo capsules administered orally daily

Treatment: Drugs: Prednisone
Prednisone administered daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Analysis: Response Rate at 48 Weeks
Timepoint [1] 0 0
48 weeks (Cumulatively up to 30 March 2020)
Primary outcome [2] 0 0
Final Analysis: Response Rate at 48 Weeks
Timepoint [2] 0 0
48 weeks (Cumulatively up to 12 July 2021)
Secondary outcome [1] 0 0
Primary Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD
Timepoint [1] 0 0
Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 30 March 2020)
Secondary outcome [2] 0 0
Final Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD
Timepoint [2] 0 0
Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021)
Secondary outcome [3] 0 0
Primary Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants
Timepoint [3] 0 0
Months 3, 6, 9, 12, 15, 18, 21, 24 (cumulatively up to 30 March 2020)
Secondary outcome [4] 0 0
Final Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants
Timepoint [4] 0 0
Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021)
Secondary outcome [5] 0 0
Primary Analysis: Response Rate at 24 Weeks
Timepoint [5] 0 0
24 weeks (Cumulatively up to 30 March 2020)
Secondary outcome [6] 0 0
Final Analysis: Response Rate at 24 Weeks
Timepoint [6] 0 0
24 weeks (Cumulatively up to 12 July 2021)
Secondary outcome [7] 0 0
Primary Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Final Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
24 weeks (Cumulatively up to 30 March 2020)
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
24 weeks (Cumulatively up to 12 July 2021)
Secondary outcome [11] 0 0
Primary Analysis: Overall Survival (OS)
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
Final Analysis: OS
Timepoint [12] 0 0
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.
Secondary outcome [13] 0 0
Primary Analysis: Duration of Response (DOR) for Participants Who Had PR or CR at Any Time
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Final Analysis: DOR for Participants Who Had PR or CR at Any Time
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Primary Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone
Timepoint [15] 0 0
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.
Secondary outcome [16] 0 0
Final Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone
Timepoint [16] 0 0
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.

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Kinghorn Cancer Centre /ID# 1140-1165 - Darlinghurst
Recruitment hospital [2] 0 0
Westmead Hospital /ID# 1140-0848 - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital /ID# 1140-0190 - Herston
Recruitment hospital [4] 0 0
Royal Children's Hospital/ID# 1140-1154 - Parkville
Recruitment hospital [5] 0 0
Royal Melbourne Hospital (RMH) /ID# 1140-0633 - Parkville
Recruitment hospital [6] 0 0
Fiona Stanley Hospital /ID# 1140-0880 - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
United States of America
State/province [23] 0 0
West Virginia
Country [24] 0 0
Austria
State/province [24] 0 0
Graz
Country [25] 0 0
Austria
State/province [25] 0 0
Linz
Country [26] 0 0
Canada
State/province [26] 0 0
British Columbia
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
China
State/province [29] 0 0
Jiangsu
Country [30] 0 0
China
State/province [30] 0 0
Beijing
Country [31] 0 0
China
State/province [31] 0 0
Guangzhou Shi
Country [32] 0 0
Croatia
State/province [32] 0 0
Zagreb
Country [33] 0 0
France
State/province [33] 0 0
Ile-de-France
Country [34] 0 0
France
State/province [34] 0 0
Meurthe-et-Moselle
Country [35] 0 0
France
State/province [35] 0 0
Amiens
Country [36] 0 0
France
State/province [36] 0 0
Grenoble
Country [37] 0 0
France
State/province [37] 0 0
Lille
Country [38] 0 0
France
State/province [38] 0 0
Nantes
Country [39] 0 0
France
State/province [39] 0 0
Paris
Country [40] 0 0
Germany
State/province [40] 0 0
Baden-Wuerttemberg
Country [41] 0 0
Germany
State/province [41] 0 0
Niedersachsen
Country [42] 0 0
Germany
State/province [42] 0 0
Dresden
Country [43] 0 0
Germany
State/province [43] 0 0
Hannover
Country [44] 0 0
Germany
State/province [44] 0 0
Munich
Country [45] 0 0
Germany
State/province [45] 0 0
Regensburg
Country [46] 0 0
Hungary
State/province [46] 0 0
Budapest
Country [47] 0 0
Italy
State/province [47] 0 0
Lazio
Country [48] 0 0
Italy
State/province [48] 0 0
Marche
Country [49] 0 0
Italy
State/province [49] 0 0
Bergamo
Country [50] 0 0
Italy
State/province [50] 0 0
Milan
Country [51] 0 0
Italy
State/province [51] 0 0
Torino
Country [52] 0 0
Italy
State/province [52] 0 0
Turin
Country [53] 0 0
Japan
State/province [53] 0 0
Aichi
Country [54] 0 0
Japan
State/province [54] 0 0
Hiroshima
Country [55] 0 0
Japan
State/province [55] 0 0
Hyogo
Country [56] 0 0
Japan
State/province [56] 0 0
Ibaraki
Country [57] 0 0
Japan
State/province [57] 0 0
Kanagawa
Country [58] 0 0
Japan
State/province [58] 0 0
Okayama
Country [59] 0 0
Japan
State/province [59] 0 0
Osaka
Country [60] 0 0
Japan
State/province [60] 0 0
Tokyo
Country [61] 0 0
Japan
State/province [61] 0 0
Kumamoto
Country [62] 0 0
Japan
State/province [62] 0 0
Sapporo
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Daegu Gwang Yeogsi
Country [64] 0 0
Korea, Republic of
State/province [64] 0 0
Seoul Teugbyeolsi
Country [65] 0 0
Korea, Republic of
State/province [65] 0 0
Seoul
Country [66] 0 0
Singapore
State/province [66] 0 0
Singapore
Country [67] 0 0
Spain
State/province [67] 0 0
Barcelona
Country [68] 0 0
Spain
State/province [68] 0 0
Sevilla
Country [69] 0 0
Spain
State/province [69] 0 0
Valencia
Country [70] 0 0
Taiwan
State/province [70] 0 0
Taichung
Country [71] 0 0
Taiwan
State/province [71] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pharmacyclics LLC.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Janssen Research & Development, LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Justin Wahlstrom, MD
Address 0 0
Pharmacyclics LLC.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://yoda.yale.edu


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.