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

NCT ID: NCT02195869

Last Updated: 2019-07-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-14

Study Completion Date

2017-09-15

Brief Summary

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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.

Detailed Description

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Conditions

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Graft Versus Host Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1b: Dose Level 1

Subjects receive daily dose of 420 mg of Ibrutinib capsules

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Phase 1b: Dose Level 2

Subjects receive daily dose of 280 mg of Ibrutinib capsules

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Phase 1b: Dose Level 3

Subjects receive daily dose of 140 mg of Ibrutinib capsules

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Phase 2

Subjects receive daily dose of recommended phase 2 dose

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Interventions

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Ibrutinib

Intervention Type DRUG

Other Intervention Names

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PCI32765

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pharmacyclics LLC.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lori Styles, MD

Role: STUDY_DIRECTOR

Pharmacyclics LLC.

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Emory University, Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 34102349 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31260802 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28924018 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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PCYC-1129-CA

Identifier Type: -

Identifier Source: org_study_id

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