Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease

NCT02195869 | Completed Phase 1 Results

• 1 other identifier: PCYC-1129-CA
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to assess the safety and clinical efficacy of ibrutinib in subjects with steroid dependent or refractory Chronic Graft Versus Host Disease.

Conditions

Graft Versus Host Disease

Keywords

PCYC1129; PCYC1129CA; 1129; Ibrutinib; PCI32765; IMBRUVICA; Pharmacyclics; PCYC; GVHD; Steroid dependent; refractory; chronic; graft versus host disease; chronic graft versus host disease; immunology

Outcome Measures

Primary Outcomes (2)

• Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD.

  Number of participants with dose-limiting toxicities as a measure of safety profile to determine recommended dose of ibrutinib

  28 treatment days after last subject enrolled in Phase 1 dose level(s).

• Phase 2: Overall Response Rate as the Percentage of Participants With Response

  Overall Response Rate is defined as the proportion of subjects who achieved complete response (CR) or partial response (PR). Response criteria are based on NIH cGVHD Response assessment (Pavletic 2006; Measurement of Therapeutic Response, ASBMT Web site).

  Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.

Secondary Outcomes (5)

• Sustained Response Rate as the Percentage of Participants With Sustained Response

  Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.

• To Evaluate the Clinical Efficacy of Ibrutinib in Steroid Dependent/Refractory cGVHD by Measuring: Duration of Response (DOR)

  Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.

• Corticosteroid Requirement Changes Over Time

  Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.

• Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Summary Score

  Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.

• Phase 2b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD

  From first dose with study drug until 30 days after the last dose of study drug, up to 36.7 months

Study Arms (4)

Phase 1b: Dose Level 1

EXPERIMENTAL

Subjects receive daily dose of 420 mg of Ibrutinib capsules

Drug: Ibrutinib

Phase 1b: Dose Level 2

EXPERIMENTAL

Subjects receive daily dose of 280 mg of Ibrutinib capsules

Drug: Ibrutinib

Phase 1b: Dose Level 3

EXPERIMENTAL

Subjects receive daily dose of 140 mg of Ibrutinib capsules

Drug: Ibrutinib

Phase 2

EXPERIMENTAL

Subjects receive daily dose of recommended phase 2 dose

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Also known as: PCI32765

Phase 1b: Dose Level 1; Phase 1b: Dose Level 2; Phase 1b: Dose Level 3; Phase 2

Eligibility Criteria

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

You may qualify if:

• Steroid dependent or refractory classic chronic GVHD disease.
• No more than 3 previous treatments for cGVHD.
• Receiving baseline systemic glucocorticoid therapy (at stable dose) for cGVHD at study entry.
• Men and women ≥18 years old.
• Karnofsky performance status ≥60.

You may not qualify if:

• Known or suspected active acute GVHD.
• Current treatment with sirolimus AND either cyclosporine or tacrolimus.
• History of treatment with a tyrosine kinase inhibitor (eg, imatinib), purine analogs or other cancer chemotherapy in the 4 weeks prior to starting study drug.
• Currently active, clinically significant cardiovascular disease.
• Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines or a recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
• Progressive underlying malignant disease including post-transplant lymphoproliferative disease.
• History of other malignancy (not including the underlying malignancy that was the indication for transplant)
• Concomitant use of warfarin or other Vitamin K antagonists
• Known bleeding disorders or hemophilia.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Concurrent use of a strong cytochrome P450(CYP) 3A inhibitor.

Sponsors & Collaborators

• Pharmacyclics LLC.: lead

Study Sites (10)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Emory University, Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (3)

• Doki N, Toyosaki M, Shiratori S, Osumi T, Okada M, Kawakita T, Sawa M, Ishikawa T, Ueda Y, Yoshinari N, Nakahara S. An Open-Label, Single-Arm, Multicenter Study of Ibrutinib in Japanese Patients With Steroid-dependent/Refractory Chronic Graft-Versus-Host Disease. Transplant Cell Ther. 2021 Oct;27(10):867.e1-867.e9. doi: 10.1016/j.jtct.2021.05.019. Epub 2021 Jun 6.

  PMID: 34102349 DERIVED

• Waller EK, Miklos D, Cutler C, Arora M, Jagasia MH, Pusic I, Flowers MED, Logan AC, Nakamura R, Chang S, Clow F, Lal ID, Styles L, Jaglowski S. Ibrutinib for Chronic Graft-versus-Host Disease After Failure of Prior Therapy: 1-Year Update of a Phase 1b/2 Study. Biol Blood Marrow Transplant. 2019 Oct;25(10):2002-2007. doi: 10.1016/j.bbmt.2019.06.023. Epub 2019 Jun 28.

  PMID: 31260802 DERIVED

• Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, Flowers ME, Logan AC, Nakamura R, Blazar BR, Li Y, Chang S, Lal I, Dubovsky J, James DF, Styles L, Jaglowski S. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017 Nov 23;130(21):2243-2250. doi: 10.1182/blood-2017-07-793786. Epub 2017 Sep 18.

  PMID: 28924018 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease; Bronchiolitis Obliterans Syndrome

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Manuela Juretic, Associate Director, Clinical Operations
• Organization: Pharmacyclics LLC, An AbbVie Company

mjuretic@pcyc.com

(408) 215.3628

Study Officials

• Lori Styles, 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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2014
• First Posted: July 21, 2014
• Study Start: July 14, 2014
• Primary Completion: September 15, 2017
• Study Completion: September 15, 2017
• Last Updated: July 11, 2019
• Results First Posted: July 11, 2019

Record last verified: 2019-06

Locations

US (10)