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

NCT02959944 | Completed Phase 3 Results FDA Drug

• 1 other identifier: PCYC-1140-IM
• Study Type: interventional
• Target: 193
• Locations: 14 countries
• Sites: 96

Brief Summary

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

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

Outcome Measures

Primary Outcomes (2)

• 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.

  48 weeks (Cumulatively up to 30 March 2020)

• 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.

  48 weeks (Cumulatively up to 12 July 2021)

Secondary Outcomes (16)

• Primary Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD

  Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 30 March 2020)

• Final Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD

  Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021)

• Primary Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants

  Months 3, 6, 9, 12, 15, 18, 21, 24 (cumulatively up to 30 March 2020)

• Final Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants

  Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021)

• Primary Analysis: Response Rate at 24 Weeks

  24 weeks (Cumulatively up to 30 March 2020)

Study Arms (2)

Ibrutinib + Prednisone

EXPERIMENTAL

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.

Drug: ibrutinib; Drug: Prednisone

Placebo + Prednisone

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Prednisone

Interventions

ibrutinib DRUG

Ibrutinib capsules administered orally daily

Also known as: IMBRUVICA®, PCI-32765

Ibrutinib + Prednisone

Placebo DRUG

Placebo capsules administered orally daily

Placebo + Prednisone

Prednisone DRUG

Prednisone administered daily

Ibrutinib + Prednisone; Placebo + Prednisone

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Pharmacyclics LLC.: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (102)

Arizona Oncology - Scottsdale - Cancer Transplant Institute Location /ID# 1140-1120

Scottsdale, Arizona, 85258-4547, United States

Location

LPCH Stanford /ID# 1140-1128

Palo Alto, California, 94304, United States

Location

Ucsf /Id# 1140-0003

San Francisco, California, 94143, United States

Location

Stanford University/Stanford Cancer Center, Pasteur Drive /ID# 1140-0400

Stanford, California, 94305, United States

Location

UCHSC Anschultz Cancer Pavilion /ID# 1140-0068

Aurora, Colorado, 80010, United States

Location

Children's National Medical Center /ID# 1140-1122

Washington D.C., District of Columbia, 20010, United States

Location

Jackson Memorial Hospital, University of Miami /ID# 1140-0647

Miami, Florida, 33136-1096, United States

Location

Florida Hospital Cancer Institute/Adventist Health System/Sunbelt, Inc /ID# 1140-1121

Orlando, Florida, 32804, United States

Location

Emory University, Winship Cancer Institute /ID# 1140-0033

Atlanta, Georgia, 30322, United States

Location

Emory University/Winship Cancer Institute /ID# 1140-1179

Atlanta, Georgia, 30322, United States

Location

University of Chicago /ID# 1140-0126

Chicago, Illinois, 60637, United States

Location

Loyola University /ID# 1140-0713

Maywood, Illinois, 60153, United States

Location

Indiana University Melvin and Bren Simon Cancer Center /ID# 1140-0010

Indianapolis, Indiana, 46202-5112, United States

Location

University of Kentucky /ID# 1140-1140

Lexington, Kentucky, 40508-2678, United States

Location

University of Louisville Hospital /ID# 1140-1131

Louisville, Kentucky, 40202, United States

Location

University of Maryland /ID# 1140-0205

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital Cancer Center /ID# 1140-0020

Boston, Massachusetts, 02114, United States

Location

Boston Childrens Hospital /ID# 1140-1615

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute /ID# 1140-0349

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer In /ID# 1140-0130

Detroit, Michigan, 48201, United States

Location

University of Minnesota /ID# 1140-0807

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic, Rochester, MN /ID# 1140-0240

Rochester, Minnesota, 55905, United States

Location

Hackensack University Medical Center/ John Theurer Cancer Center /ID# 1140-0343

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of NJ /ID# 1140-0803

New Brunswick, New Jersey, 08903, United States

Location

New York Presbyterian Hospital/Weill Cornell Med College /ID# 1140-0200

New York, New York, 10021, United States

Location

Stony Brook University Medical Center /ID# 1140-0719

New York, New York, 10021, United States

Location

Columbia University Medical Center, MS-CHONY /ID# 1140-1124

New York, New York, 10032-1559, United States

Location

Weill Cornell Physicians - Hematologic Malignancies & Bone Marrow Transplant /ID# 1140-0019

New York, New York, 10065, United States

Location

University of Rochester Cancer Center /ID# 1140-0127

Rochester, New York, 14642-0001, United States

Location

Montefiore Medical Center - Moses Campus /ID# 1140-0120

The Bronx, New York, 10467, United States

Location

University of North Carolina - Lineberger Comprehensive Cancer Center /ID# 1140-1133

Chapel Hill, North Carolina, 27516, United States

Location

Univ Hosp Cleveland /ID# 1140-0941

Cleveland, Ohio, 44106, United States

Location

University of Pittsburgh - UPMC (Hillman Cancer Center) /ID# 1140-0050

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical University of South Carolina, MUSC /ID# 1140-0738

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center Vanderbilt Ingram Cancer Center /ID# 1140-0024

Nashville, Tennessee, 37232-5280, United States

Location

Methodist San Antonio /ID# 1140-1118

San Antonio, Texas, 78229-3710, United States

Location

Fred Hutchinson Cancer Research Center /ID# 1140-0404

Seattle, Washington, 98109, United States

Location

West Virginia University /ID# 1140-1090

Morgantown, West Virginia, 26506, United States

Location

The Kinghorn Cancer Centre /ID# 1140-1165

Darlinghurst, New South Wales, 2010, Australia

Location

Westmead Hospital /ID# 1140-0848

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane and Women's Hospital /ID# 1140-0190

Herston, Queensland, 4029, Australia

Location

Royal Children's Hospital/ID# 1140-1154

Parkville, Victoria, 3052, Australia

Location

Royal Melbourne Hospital (RMH) /ID# 1140-0633

Parkville, Victoria, 3052, Australia

Location

Fiona Stanley Hospital /ID# 1140-0880

Perth, Western Australia, 6000, Australia

Location

Univ. Klinik for Innere Medizin, Klinische Abteilung for Hematologie, Graz /ID# 1140-0373

Graz, 8036, Austria

Location

Krankenhaus der Elisabethinen Linz /ID# 1140-0849

Linz, 4020, Austria

Location

University of British Columbia (UBC) - Vancouver General Hospital (VGH) /ID# 1140-1166

Vancouver, British Columbia, V5Z 1M9, Canada

Location

The Ottawa Hospital Regional Cancer Center /ID# 1140-0159

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre /ID# 1140-0043

Toronto, Ontario, M5G 2M9, Canada

Location

CHU Sainte-Justine /ID# 1140-1143

Montreal, Quebec, H3T 1C5, Canada

Location

The First Affiliated Hospital of Soochow University /ID# 1140-1208

Suzhou, Jiangsu, 215006, China

Location

Chinese PLA General Hospital /ID# 1140-1198

Beijing, 100853, China

Location

Nanfang Hospital /ID# 1140-1379

Guangzhou, 510000, China

Location

UHC Zagreb /ID# 1140-1169

Zagreb, 10000, Croatia

Location

Hopital de Brabois /ID# 1140-0775

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511, France

Location

CHU Amiens Groupe hospitalier Sud /ID# 1140-1205

Amiens, 80054, France

Location

CHU de GRENOBLE Alpes /ID# 1140-1058

Grenoble, 38043, France

Location

Centre Hospitalier Regional Universitaire de Lille /ID# 1140-0750

Lille, 59037, France

Location

CHU de Nantes /ID# 1140-0520

Nantes, 44093, France

Location

Groupe Hospitalier Pitie-Salpetriere /ID# 1140-0918

Paris, 33000, France

Location

Hopital Saint-Louis - Institut Hematologie Centre Hayem CHU /ID# 1140-0735

Paris, Île-de-France Region, 75010, France

Location

Robert Bosch Hospital /ID# 1140-1160

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

Universitatsklinikum Munster /ID# 1140-1195

Munster, Lower Saxony, 48149, Germany

Location

Universitaetsklinikum Dresden /ID# 1140-1367

Dresden, 01307, Germany

Location

Hannover Medical School /ID# 1140-1141

Hanover, 30625, Germany

Location

Dr. Haunerschen Kinderspital /ID# 1140-1142

Munich, 80337, Germany

Location

University Hospital of Regensburg /ID# 1140-1446

Regensburg, 93053, Germany

Location

St. Laszlo Hospital /ID# 1140-1164

Budapest, 1097, Hungary

Location

IRCCS Ospedale Pediatrico Bambino Gesu /ID# 1140-1150

Rome, Lazio, 00165, Italy

Location

A.O. Univ. Ospedali Riuniti /ID# 1140-0932

Ancona, The Marches, 60126, Italy

Location

ASST Papa Giovanni XXIII /ID# 1140-1231

Bergamo, 24127, Italy

Location

Ospedale San Raffaele IRCCS /ID# 1140-0523

Milan, 20132, Italy

Location

University of Torino /ID# 1140-1268

Torino, 10124, Italy

Location

Centro Trapianti Cellule Staminali, Ospedale Infantile Regina Margherita /ID# 1140-1156

Turin, 10126, Italy

Location

Anjou Kousei Hospital /ID# 1140-1435

Anjo, Aichi-ken, 446-8602, Japan

Location

Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital /ID# 1140-1437

Hiroshima, Hiroshima, 730-8619, Japan

Location

Kobe City Medical Center General Hospital /ID# 1140-1438

Kobe, Hyōgo, 650-0047, Japan

Location

Hyogo College of Medicine College Hospital /Id# 1140-1434

Nishinomiya-shi, Hyōgo, 663-8501, Japan

Location

Duplicate_University of Tsukuba Hospital /ID# 1140-1445

Tsukuba, Ibaraki, 305-8576, Japan

Location

Tokai University Hospital /ID# 1140-1444

Isehara-shi, Kanagawa, 259-1193, Japan

Location

Duplicate_Kurashiki Central Hospital /ID# 1140-1442

Kurishiki-shi, Okayama-ken, 710-8602, Japan

Location

Okayama University Hospital /ID# 1140-1430

Okayama, Okayama-ken, 700-8558, Japan

Location

Osaka Women's and Children's Hospital /ID# 1140-1440

Izumi-Shi, Osaka, 594-1101, Japan

Location

Osaka City University Hospital /ID# 1140-1157

Osaka, Osaka, 545-8586, Japan

Location

Dup_Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 1140-1439

Bunkyo-ku, Tokyo, 113-8677, Japan

Location

National Center for Child Health and Development /ID# 1140-1443

Setagaya-ku, Tokyo, 157-8535, Japan

Location

Kumamoto Medical Center /ID# 1140-1431

Kumamoto, 860-0008, Japan

Location

Hokkaido University Hospital /ID# 1140-1436

Sapporo, 060-8648, Japan

Location

National University Cancer Institute - National University Health System /ID# 1140-1155

Singapore, 119228, Singapore

Location

Singapore General Hospital /ID# 1140-1162

Singapore, 169608, Singapore

Location

Kyungpook National Univ Hosp /ID# 1140-1153

Daegu, Daegu Gwang Yeogsi, 41944, South Korea

Location

Yonsei University Health System, Severance Hospital /ID# 1140-0927

Seodaemun-gu, Seoul Teugbyeolsi, 03722, South Korea

Location

Samsung Medical Center /ID# 1140-0925

Seoul, Seoul Teugbyeolsi, 06351, South Korea

Location

Cath Univ Seoul St Mary's Hosp /ID# 1140-0928

Seoul, Seoul Teugbyeolsi, 06591, South Korea

Location

SoonChunHyang University Seoul /ID# 1140-1163

Seoul, 04401, South Korea

Location

Asan Medical Center /ID# 1140-0963

Seoul, 05505, South Korea

Location

Hospital Clinic /ID# 1140-0533

Barcelona, 08036, Spain

Location

Hospital Santa Creu i Sant Pau /ID# 1140-0535

Barcelona, 08041, Spain

Location

Hospital Universitario Virgen del Rocio /ID# 1140-0863

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia /ID# 1140-1145

Valencia, 46010, Spain

Location

China Medical University Hosp /ID# 1140-1199

Taichung, Taichung, 40447, Taiwan

Location

National Taiwan Univ Hosp /ID# 1140-1184

Taipei City, Taipei, 10002, Taiwan

Location

Related Publications (1)

• Miklos DB, Abu Zaid M, Cooney JP, Albring JC, Flowers M, Skarbnik AP, Yakoub-Agha I, Ko BS, Bruno B, Waller EK, Yared J, Sohn SK, Bulabois CE, Teshima T, Jacobsohn D, Greinix H, Mokatrin A, Lee Y, Wahlstrom JT, Styles L, Socie G. Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study. J Clin Oncol. 2023 Apr 1;41(10):1876-1887. doi: 10.1200/JCO.22.00509. Epub 2023 Jan 6.

  PMID: 36608310 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Graft vs Host Disease

Interventions

ibrutinib; Prednisone

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Justin Wahlstrom MD
• Organization: Pharmacyclics, LLC

jwahlstrom@pcyc.com

669-215-7210

Study Officials

• Justin Wahlstrom, MD

  Pharmacyclics LLC.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: November 9, 2016
• Study Start: May 11, 2017
• Primary Completion: March 27, 2020
• Study Completion: July 12, 2021
• Last Updated: March 30, 2023
• Results First Posted: May 4, 2021

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

FR (7); KR (6); JP (14); AU (2); CA (4); ES (4); SG (2); IT (6); US (38); CN (3); CR (1); HU (1); DE (6); TW (2)