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Graft Versus Host DiseasePhase 1/2NCT02195869

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

A Phase 1/2 study testing Ibrutinib in people with Graft Versus Host Disease, run by Pharmacyclics LLC. at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft Versus Host Disease
What is being tested?
Ibrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
10 sitesUnited States
Study dates
14 Jul 2014to 15 Sep 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Emory University, Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • City of Hope Medical Center

    Duarte, California, 91010

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic

    Nashville, Tennessee, 37232

  • University of California, San Francisco

    San Francisco, California, 94143

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease

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.

Being tested
Ibrutinib
Keywords
PCYC1129, PCYC1129CA, 1129, Ibrutinib, PCI32765, IMBRUVICA, Pharmacyclics, PCYC, GVHD, Steroid dependent, refractory, chronic, graft versus host disease, chronic graft versus host disease, immunology
Medical subject headings
Graft vs Host Disease, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02195869
Study groupRoleWhat they receive
Phase 1b: Dose Level 1ExperimentalSubjects receive daily dose of 420 mg of Ibrutinib capsules
Receives: Drug: Ibrutinib
Phase 1b: Dose Level 2ExperimentalSubjects receive daily dose of 280 mg of Ibrutinib capsules
Receives: Drug: Ibrutinib
Phase 1b: Dose Level 3ExperimentalSubjects receive daily dose of 140 mg of Ibrutinib capsules
Receives: Drug: Ibrutinib
Phase 2ExperimentalSubjects receive daily dose of recommended phase 2 dose
Receives: Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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).

    Measured: 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)

  1. Sustained Response Rate as the Percentage of Participants With Sustained Response

    For subjects who achieved an NIH-defined CR or PR, the proportion of subjects who achieved CR or PR that was sustained for at least 20 weeks (140 days). Intermittent SD was also acceptable.

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

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

    For subjects who achieved an NIH-defined CR or PR, the interval between the date of initial documentation of a response and the date of first documented evidence of PD, death, or date of censoring if applicable.

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

  3. Corticosteroid Requirement Changes Over Time

    Average daily corticosteroid dose assessed each week.

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

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

    Subject reported improvement in symptom burden. The symptom burden will be measured according to the Lee cGVHD Symptom Scale. A change in >7 points on the Lee cGVHD Symptom Scale will be considered significant and relates to improvement in quality of life.

    A score is calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. A total summary score is calculated as the average of these 7 subscales if at least 4 subscales have valid scores.

    There are 7 subscales (Skin, Energy, Lung, Eye, Nutrition, Mouth and Psychological) with ratings as follow: 0- Not at all, 1- Slightly, 2 Moderately, 3 Quite a bit, 4-Extremely; with a lower values representing a better outcome.

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

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

    Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2014 (estimated)
  2. Study start14 Jul 2014
  3. Primary completion15 Sep 2017
  4. Study completion15 Sep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02195869
Sponsor's protocol ID
PCYC-1129-CA
Status last verified
Jun 2019
First submitted
11 Jul 2014
Last updated
11 Jul 2019

Publications

  • 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.

    PubMed 34102349

  • 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.

    PubMed 31260802

  • 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.

    PubMed 28924018

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ibrutinib in people with Graft Versus Host Disease, run by Pharmacyclics LLC. at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD. (time frame: 28 treatment days after last subject enrolled in Phase 1 dose level(s).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02195869, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2019.

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