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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Graft Versus Host Disease	Drug: Ibrutinib	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	45 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease
Study Start Date :	July 2014
Estimated Primary Completion Date :	December 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Phase 1b: Dose Level 1; Ibrutinib PO administered daily	Drug: Ibrutinib; Other Name: PCI32765
Experimental: Phase 1b: Dose Level 2; Ibrutinib (PO) administered daily	Drug: Ibrutinib; Other Name: PCI32765
Experimental: Phase 1b: Dose Level 3; Ibrutinib (PO) administered daily	Drug: Ibrutinib; Other Name: PCI32765
Experimental: Phase 2; Ibrutinib (PO) administered daily for 18 months	Drug: Ibrutinib; Other Name: PCI32765

Outcome Measures

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Primary Outcome Measures :

1. Phase 1b: Number of dose-limiting toxicities as a measure of safety profile to determine recommended dose of ibrutinib [ Time Frame: 28 treatment days after last subject enrolled in Phase 1 dose level(s). ]
2. Phase 2 (Efficacy): Overall cGVHD response rate defined as the proportion of evaluable subjects who achieve a [NIH-defined Complete Response (CR) and Partial Response (PR)] over all subjects who were treated with RP2D [ Time Frame: When the last subject completes 6 months of treatment. ]

Secondary Outcome Measures :

1. Failure Free Survival (FFS) [ Time Frame: When the last subject completes 6 and 12 months of treatment. ]
2. Change in symptom burden by the Lee cGVHD Symptom Scale [ Time Frame: Approximately 18 months after last subject is enrolled or up to disease progression, whichever occurs first. ]
3. Corticosteroid requirement changes over Time [ Time Frame: Approximately 18 months after last subject is enrolled or up to disease progression, whichever occurs first. ]
4. Number of subjects with Adverse Events (AE) as a measure of safety and tolerability of ibrutinib [ Time Frame: Approximately 18 months after last subject is enrolled. ]
5. Determine the plasma pharmacokinetics of ibrutinib and the metabolite, PCI-45227 [ Time Frame: Samples will be collected during the first two weeks of subject receiving study drug and will be assessed approximately 1 month after completion of the PK sample collections of the last subject enrolled at each dose level. ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Locations

United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
University of California, San Francisco
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Georgia
Emory University, Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic
Nashville, Tennessee, United States, 37232
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Pharmacyclics LLC.

Investigators

Study Director:	Lori Styles, MD	Pharmacyclics LLC.

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Pharmacyclics LLC.
ClinicalTrials.gov Identifier:	NCT02195869 History of Changes
Other Study ID Numbers:	PCYC-1129-CA
First Posted:	July 21, 2014
Last Update Posted:	April 14, 2016
Last Verified:	April 2016

Keywords provided by Pharmacyclics LLC.:

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

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases