Chronic GVHDPhase 2NCT04294641
Front Line Ibrutinib Without Corticosteroids for Newly Diagnosed Chronic Graft-versus-Host Disease
A Phase 2 study testing Ibrutinib, ECG and PFT's in people with Chronic GVHD, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
Background: Chronic Graft Versus Host Disease (cGVHD) can occur after a person has had a stem cell or bone marrow transplant. In cGVHD, the donor cells attack the recipient's body. Researchers want to see if a drug called ibrutinib can block one of the proteins that lead to the immune reaction that causes cGVHD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic GVHD
- What is being tested?
- Ibrutinib, ECG and PFT's
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 May 2021to 1 Oct 2024
- Phase
- Phase 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
- Newly diagnosed moderate or severe chronic Graft versus Host Disease (GvHD) (according to the 2014 National Institutes of Health (NIH) Consensus Criteria, requiring systemic immunosuppression.
- History of prior allogeneic Hematopoietic Stem Cell Transplant (HSCT) (any donors, conditioning regimens and graft sources are allowed).
- Subjects may have ongoing acute GvHD features (e.g., erythematous rash, elevated liver enzymes, diarrhea) which are in the opinion of the investigator responding to therapy.
- Stable doses of other immunosuppressive medications (e.g., calcineurin inhibitors, mycophenolate mofetil, rapamune, etc.) with no dose increase in the 2 weeks prior to study treatment initiation. Doses may be adjusted for trough levels.
- Age greater than or equal to 18 years old.
- Karnofsky performance status greater than or equal to 60%.
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- Laboratory parameters as defined below:
- Serum creatinine less than or equal to 2.0 x upper limit of normal (ULN).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN (less than or equal to 5 x ULN if unequivocal liver GvHD).
- Total bilirubin less than or equal to 3 x ULN.
- Absolute neutrophil count greater than or equal to 1.0 x 10(9)/L (no growth factor support allowed).
- Platelets > 50 x 10(9)/L (no transfusions allowed less than or equal to 7 days prior to enrollment).
- Ability to understand and willingness to sign a written informed consent form.
- The effects of ibrutinib on the developing fetus are unknown. For this reason and because tyrosine kinase inhibitors may be teratogenic, female subjects of childbearing potential and men must agree to use highly effective methods of birth control (hormonal or barrier method of birth control; abstinence) prior to study entry, during the period of therapy, and for 30 days after the last dose of study drug.
Who cannot join
- Relapsed or progressive malignant disease (other than minimal residual disease).
- History of other malignant diseases, including post-transplant lymphoproliferative disease, with the following exceptions:
- Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to prior to study treatment initiation and felt to be at low risk for recurrence.
- Adequately treated non-melanomatous skin cancer or lentigo malignant melanoma without current evidence of disease.
- Adequately treated cervical carcinoma in situ without current evidence of disease.
- Received previous systemic treatment for chronic GvHD other than less than or equal to 0.5 mg/kg/day of prednisone equivalent for more than 7 days. Subject may be on steroids that were used to treat acute GvHD and then developed chronic GvHD before completing a taper. At the time of enrollment, the dose should be less than or equal to 0.5 mg/kg/day of prednisone equivalent with no dose increase in the preceding 2 weeks before study treatment initiation.
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- Prior or current treatment with:
- Ibrutinib since the time of transplant (participants may have received ibrutinib prior to transplant for indications other than chronic GvHD).
- Extracorporeal photopheresis (ECP) for acute GvHD less than or equal to 2 weeks prior to study treatment initiation; including any treatment with ECP for chronic GvHD.
- Rituximab or other anti-B cell specific antibodies less than or equal to 4 weeks prior to study treatment initiation.
- Any systemic investigational agents less than or equal to 4 weeks prior to study treatment initiation.
- Impaired cardiac function including any one of the following:
- Myocardial infarction, unstable angina or acute coronary syndrome less than or equal to 6 months prior to study treatment initiation.
- Class 3 or 4 congestive heart failure, uncontrolled arrhythmia or uncontrolled hypertension at any time.
- Uncontrolled infections (including prior aspergillosis) not responsive to antibiotics, antiviral medicines, or antifungal medicines.
- Known bleeding disorder or subjects who received a strong cytochrome P450 (CYP) 3A inhibitor less than or equal to 7 days prior to the first dose of ibrutinib or requirement for continuous treatment with a strong CYP3A inhibitor.
- Active hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result to be enrolled.
- Known hypersensitivity to ibrutinib.
- Pregnant women are excluded from this study because ibrutinib has potential for teratogenic and abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ibrutinib, breastfeeding should be discontinued if the mother is treated with ibrutinib. Women who are planning to become pregnant and men who plan to father a child while enrolled in this study or less than or equal to 30 days after the last dose of study drug are excluded.
- Any other reason at the discretion of the investigators and documented in the medical record that may raise concerns about the subject safety or ability to participate on this study.
- Currently active, severe hepatic impairment Child-Pugh class C according to the Child Pugh classification.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Washington University, School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Study of Front Line Ibrutinib Without Corticosteroids for Newly Diagnosed Chronic Graft-versus-Host Disease
Background:
- Chronic Graft Versus Host Disease (cGVHD) can occur after a person has had a stem cell or bone marrow transplant. In cGVHD, the donor cells attack the recipient's body. Researchers want to see if a drug called ibrutinib can block one of the proteins that lead to the immune reaction that causes cGVHD.
Read more
Objective:
- To see if ibrutinib as a first-line treatment can help people with newly diagnosed cGVHD.
Eligibility:
- People age 18 and older with newly diagnosed moderate or severe cGVHD
Design:
- Participants will be screened with:
- Medical and medicine histories
- Physical exam and vital signs
- Electrocardiograms (to measure heart function)
- Assessment of their ability to perform daily activities
- Blood and urine tests
- Assessment of their general well-being.
- Participants will visit the Clinical Center every 2 weeks for the first 2 months. Then they will visit every 4 weeks.
- Participants will take ibrutinib by mouth once every day of every cycle. One cycle is 28 days. Treatment will last up to 2 years. Participants will keep a medicine diary.
- Participants will take tests to measure lung function. They may have computed tomography scans of their chest. They will complete questionnaires about their symptoms and how cGVHD is affecting their body and quality of life. They will repeat the screening tests.
- Participants may have optional blood tests and/or skin biopsies to better understand the drugs effect on the body.
- Participants will be contacted by phone 30 days after treatment ends. They will also be contacted once a year for 2 years to discuss how they are feeling and if they have taken any other medicines to treat cGVHD.
Read the detailed description
Background:
- Chronic graft-versus-host disease (GvHD) is the leading cause of late morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation (alloHSCT), occurring in 40-60% long-term survivors.
- Chronic GvHD occurs due to the dysfunctional peripheral tolerance during post-transplant hematopoietic reconstitution that allows the development and persistence of alloreactive donor-derived T and B cells.
- Prednisone is the front-line therapy; however, about 50% of participants have steroid-refractory disease and there is no standard second-line therapy.
- The most attractive approach for controlling chronic GvHD would be early therapy intervention which could prevent the most severe and irreversible clinical manifestations.
- Anti-B-cell therapy delivered early in chronic GvHD could be effective and steroid-sparing.
- Ibrutinib, reversible small molecule inhibitor of Brutons tyrosine kinase, has been shown to be well-tolerated and effective in phase 1b/2 trial for steroid refractory chronic GvHD.
Objective:
-To evaluate efficacy of ibrutinib as a first-line treatment for persons with newly diagnosed chronic GvHD by measuring the overall response rate (complete response [CR] + partial response [PR]) at 6 months, according to the 2014 National Institutes of Health (NIH) Consensus Criteria
Eligibility:
- Newly diagnosed, moderate or severe chronic GvHD according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression
- Age greater than or equal to 18 years old
- Karnofsky performance status greater than or equal to 60%
- History of prior alloHSCT; any donors, conditioning regimens and graft sources are allowed
- Adequate cardiac, hepatic and other organ function
- Adequate laboratory parameters
Design:
- Multi-center, non-randomized, phase II study
- Two-stage design will be used to determine the overall response rate (CR + PR) at 6 months
- Continuous daily dose of ibrutinib 420 mg by mouth, with the potential for dose reductions to 280 mg and 140 mg
- The accrual ceiling will be set at 40 participants, allowing for a total of up to 28 evaluable subjects.
- Conditions
- Chronic GVHD
- Being tested
- Ibrutinib, ECG, PFT's, CT, Steroid pulse (prednisone)
- Keywords
- Immunosuppressive Therapy, Kinase Inhibitors, steroid pulses, Hematologic Malignancies, alloHSCT
- Medical subject headings
- Bronchiolitis Obliterans Syndrome, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica
140 mg capsules for a dose of 420 mg daily by mouth for up to 12 months.
ECGDiagnostic test
Also called Electrocardiogram
At screening.
PFT'sDiagnostic test
Also called Pulmonary function tests
Participants should have PFTs if not performed ≤3 months prior to start of study treatment and Cycle 7, Day 1 (6 months).
Optional at Cycle 12, Day 28 (12 months) and Cycle 24, Day 28 (24 months).
CTDiagnostic test
Also called Computed tomography
Non-contrast CT at baseline and later during the study if clinically indicated.
Steroid pulse (prednisone)Drug
Also called Rayos, Prednisone Intensol, Deltasone
0.5-2mg/kg/day allowed for clinical disease stabilization during first 4 weeks after starting Ibrutinib.
VoriconazoleDrug
Also called Vfend, Vfend IV
At any dose.
PosaconazoleDrug
Also called Noxafil
As clinically indicated. At doses less than or equal to suspension 200 mg twice a day (BID) if ibrutinib dose modified to 280 mg once daily.
OR Posaconazole suspension 200 mg three times a day (TID) or 400 mg BID if Ibrutinib dose modified to 140 mg once daily.
OR Posaconazole injection intravenous (IV) injection 300 mg once daily; or delayed-release capsules 300 mg once daily if Ibrutinib dose modified to 140 mg once daily..
AzithromycinDrug
Also called AzaSite, Zithromax, Zithromax Z-Pak
Treat or prevent bronchiolitis obliterans.
MontelukastDrug
Also called Singulair
Treat or prevent bronchiolitis obliterans.
BudesonideDrug
Also called Entocort, Uceris, Rhinocort Allergy
Treat or prevent gastrointestinal acute graft-versus host disease (GvHD).
BeclomethasoneDrug
Also called Beclometasone, beclomethasone dipropionate, Qvar
Treat or prevent gastrointestinal acute graft-versus host disease (GvHD).
FilgrastimOther
Also called Neupogen
Neutrophil growth factor permitted per institutional policy
PegfilgrastimOther
Also called Neulasta
Neutrophil growth factor permitted per institutional policy.
ErythropoietinOther
Also called haematopoietin, haemopoietin
Red cell growth factor permitted per institutional policy.
TransfusionsOther
According to institutional policy.
Oral/Skin biopsyProcedure or surgery
Optional. Baseline, Cycle 7, Day 1 (6 months), Cycle 12, Day 28 (12 months) and Cycle 24, Day 28.
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib Without Corticosteroids | Experimental | Determine response rate via continuous daily dose by mouth to determine efficacy Receives: Drug: Ibrutinib; Diagnostic Test: ECG; Diagnostic Test: PFT's; Diagnostic Test: CT; Drug: Steroid pulse (prednisone); Drug: Voriconazole; Drug: Posaconazole; Drug: Azithromycin; Drug: Montelukast; Drug: Budesonide; Drug: Beclomethasone; Other: Filgrastim; Other: Pegfilgrastim; Other: Erythropoietin; Other: Transfusions; Procedure: Oral/Skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fraction of Participants With an Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Reported With an 80% Confidence Interval at 6 Months
To evaluate the efficacy of Ibrutinib as a first-line treatment for persons with newly diagnosed chronic graft-versus-host disease (GvHD) overall response rate was measured using the 2014 National Institutes of Health (NIH) consensus criteria and reported with an 80% confidence interval. CR is defined as complete resolution in all of signs and symptoms at all affected organs or tissues. PR is defined as improvement in ≥1 organ or tissue with no progression in any other affected organ or tissue.
Measured: At 6 months
Fraction of Participants With an Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Reported With an 95% Confidence Interval at 6 Months
To evaluate the efficacy of Ibrutinib as a first-line treatment for persons with newly diagnosed chronic graft-versus-host disease (GvHD) overall response rate was measured using the 2014 National Institutes of Health (NIH) consensus criteria and reported with a 95% confidence interval. CR is defined as complete resolution in all of signs and symptoms at all affected organs or tissues. PR is defined as improvement in ≥1 organ or tissue with no progression in any other affected organ or tissue.
Measured: At 6 months
Secondary outcomes (3)
Fraction of Grade 3 and Grade 4 Serious and/or Non-serious Adverse Events in Participants With Newly Diagnosed Chronic Graft-versus-host Disease (GvHD)
Safety of the agent will be determined by the fraction of grade of 3 and 4 serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe, and Grade 4 is life-threatening.
Measured: Adverse events are captured from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the participant received the last study drug administration.
Failure-free Survival (FFS)
Time to event endpoint failure free survival will be determined using a Kaplan-Meier curve and confidence intervals is calculated using the Brookmeyer-Crowley method. Failure-free survival (FFS) is defined as survival (from enrollment) without death, relapse of the underlying malignancy, or the addition of a new systemic chronic graft-versus-host-disease (GVHD) treatment.
Measured: Participants were followed from enrollment without death, relapse or new GVHD treatment up to 14 months
Fraction of Participants Alive at 24 Months Follow-up Post-treatment
Survival will be determined using a Kaplan-Meier curve at 24 months.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2020
- Study start10 May 2021
- Primary completion24 Jun 2024
- Study completion1 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic GVHDStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, James Gulley, M.D., National Cancer Institute (NCI)
- Investigators
- Steven Z Pavletic, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04294641
- Sponsor's protocol ID
- 200058
- Other IDs
- 20-C-0058
- Status last verified
- Jan 2026
- First submitted
- 3 Mar 2020
- Last updated
- 23 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Front Line Ibrutinib Without Corticosteroids for Newly Diagnosed Chronic Graft-versus-Host Disease
- ClinicalTrials.gov ID
- NCT04294641
- Acronym / sponsor ID
- 200058
- Conditions
- Chronic GVHD
- Keywords
- Immunosuppressive Therapy, Kinase Inhibitors, steroid pulses, Hematologic Malignancies, alloHSCT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 10 May 2021 (actual)
- Primary completion
- 24 Jun 2024 (actual)
- Study completion
- 1 Oct 2024 (actual)
- First posted
- 4 Mar 2020 (actual)
- Results
- Posted 22 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Chronic Graft Versus Host Disease (cGVHD) can occur after a person has had a stem cell or bone marrow transplant. In cGVHD, the donor cells attack the recipient's body. Researchers want to see if a drug called ibrutinib can block one of the proteins that lead to the immune reaction that causes cGVHD.
Objective:
- To see if ibrutinib as a first-line treatment can help people with newly diagnosed cGVHD.
Eligibility:
- People age 18 and older with newly diagnosed moderate or severe cGVHD
Design:
- Participants will be screened with:
- Medical and medicine histories
- Physical exam and vital signs
- Electrocardiograms (to measure heart function)
- Assessment of their ability to perform daily activities
- Blood and urine tests
- Assessment of their general well-being.
- Participants will visit the Clinical Center every 2 weeks for the first 2 months. Then they will visit every 4 weeks.
- Participants will take ibrutinib by mouth once every day of every cycle. One cycle is 28 days. Treatment will last up to 2 years. Participants will keep a medicine diary.
- Participants will take tests to measure lung function. They may have computed tomography scans of their chest. They will complete questionnaires about their symptoms and how cGVHD is affecting their body and quality of life. They will repeat the screening tests.
- Participants may have optional blood tests and/or skin biopsies to better understand the drugs effect on the body.
- Participants will be contacted by phone 30 days after treatment ends. They will also be contacted once a year for 2 years to discuss how they are feeling and if they have taken any other medicines to treat cGVHD.
Detailed description
Background:
- Chronic graft-versus-host disease (GvHD) is the leading cause of late morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation (alloHSCT), occurring in 40-60% long-term survivors.
- Chronic GvHD occurs due to the dysfunctional peripheral tolerance during post-transplant hematopoietic reconstitution that allows the development and persistence of alloreactive donor-derived T and B cells.
- Prednisone is the front-line therapy; however, about 50% of participants have steroid-refractory disease and there is no standard second-line therapy.
- The most attractive approach for controlling chronic GvHD would be early therapy intervention which could prevent the most severe and irreversible clinical manifestations.
- Anti-B-cell therapy delivered early in chronic GvHD could be effective and steroid-sparing.
- Ibrutinib, reversible small molecule inhibitor of Brutons tyrosine kinase, has been shown to be well-tolerated and effective in phase 1b/2 trial for steroid refractory chronic GvHD.
Objective:
-To evaluate efficacy of ibrutinib as a first-line treatment for persons with newly diagnosed chronic GvHD by measuring the overall response rate (complete response [CR] + partial response [PR]) at 6 months, according to the 2014 National Institutes of Health (NIH) Consensus Criteria
Eligibility:
- Newly diagnosed, moderate or severe chronic GvHD according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression
- Age greater than or equal to 18 years old
- Karnofsky performance status greater than or equal to 60%
- History of prior alloHSCT; any donors, conditioning regimens and graft sources are allowed
- Adequate cardiac, hepatic and other organ function
- Adequate laboratory parameters
Design:
- Multi-center, non-randomized, phase II study
- Two-stage design will be used to determine the overall response rate (CR + PR) at 6 months
- Continuous daily dose of ibrutinib 420 mg by mouth, with the potential for dose reductions to 280 mg and 140 mg
- The accrual ceiling will be set at 40 participants, allowing for a total of up to 28 evaluable subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib Without Corticosteroids | Experimental | Drug: Ibrutinib, Diagnostic Test: ECG, Diagnostic Test: PFT's, Diagnostic Test: CT, Drug: Steroid pulse (prednisone), Drug: Voriconazole, Drug: Posaconazole, Drug: Azithromycin, Drug: Montelukast, Drug: Budesonide, Drug: Beclomethasone, Other: Filgrastim, Other: Pegfilgrastim, Other: Erythropoietin, Other: Transfusions, Procedure: Oral/Skin biopsyDetermine response rate via continuous daily dose by mouth to determine efficacy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
Key exclusion criteria (21 listed)
- Relapsed or progressive malignant disease (other than minimal residual disease).
- History of other malignant diseases, including post-transplant lymphoproliferative disease, with the following exceptions:
- Received previous systemic treatment for chronic GvHD other than less than or equal to 0.5 mg/kg/day of prednisone equivalent for more than 7 days. Subject may be on steroids that were used to treat acute GvHD and then developed chronic GvHD before completing a taper. At the time of enrollment, the dose should be less than or equal to 0.5 mg/kg/day of prednisone equivalent with no dose increase in the preceding 2 weeks before study treatment initiation.
- Prior or current treatment with:
- Impaired cardiac function including any one of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: Imbruvica140 mg capsules for a dose of 420 mg daily by mouth for up to 12 months. | Drug | Ibrutinib Without Corticosteroids |
| ECGAlso: ElectrocardiogramAt screening. | Diagnostic test | Ibrutinib Without Corticosteroids |
| PFT'sAlso: Pulmonary function testsParticipants should have PFTs if not performed ≤3 months prior to start of study treatment and Cycle 7, Day 1 (6 months). Optional at Cycle 12, Day 28 (12 months) and Cycle 24, Day 28 (24 months). | Diagnostic test | Ibrutinib Without Corticosteroids |
| CTAlso: Computed tomographyNon-contrast CT at baseline and later during the study if clinically indicated. | Diagnostic test | Ibrutinib Without Corticosteroids |
| Steroid pulse (prednisone)Also: Rayos, Prednisone Intensol, Deltasone0.5-2mg/kg/day allowed for clinical disease stabilization during first 4 weeks after starting Ibrutinib. | Drug | Ibrutinib Without Corticosteroids |
| VoriconazoleAlso: Vfend, Vfend IVAt any dose. | Drug | Ibrutinib Without Corticosteroids |
| PosaconazoleAlso: NoxafilAs clinically indicated. At doses less than or equal to suspension 200 mg twice a day (BID) if ibrutinib dose modified to 280 mg once daily. OR Posaconazole suspension 200 mg three times a day (TID) or 400 mg BID if Ibrutinib dose modified to 140 mg once daily. OR Posaconazole injection intravenous (IV) injection 300 mg once daily; or delayed-release capsules 300 mg once daily if Ibrutinib dose modified to 140 mg once daily.. | Drug | Ibrutinib Without Corticosteroids |
| AzithromycinAlso: AzaSite, Zithromax, Zithromax Z-PakTreat or prevent bronchiolitis obliterans. | Drug | Ibrutinib Without Corticosteroids |
| MontelukastAlso: SingulairTreat or prevent bronchiolitis obliterans. | Drug | Ibrutinib Without Corticosteroids |
| BudesonideAlso: Entocort, Uceris, Rhinocort AllergyTreat or prevent gastrointestinal acute graft-versus host disease (GvHD). | Drug | Ibrutinib Without Corticosteroids |
| BeclomethasoneAlso: Beclometasone, beclomethasone dipropionate, QvarTreat or prevent gastrointestinal acute graft-versus host disease (GvHD). | Drug | Ibrutinib Without Corticosteroids |
| FilgrastimAlso: NeupogenNeutrophil growth factor permitted per institutional policy | Other | Ibrutinib Without Corticosteroids |
| PegfilgrastimAlso: NeulastaNeutrophil growth factor permitted per institutional policy. | Other | Ibrutinib Without Corticosteroids |
| ErythropoietinAlso: haematopoietin, haemopoietinRed cell growth factor permitted per institutional policy. | Other | Ibrutinib Without Corticosteroids |
| TransfusionsAccording to institutional policy. | Other | Ibrutinib Without Corticosteroids |
| Oral/Skin biopsyOptional. Baseline, Cycle 7, Day 1 (6 months), Cycle 12, Day 28 (12 months) and Cycle 24, Day 28. | Procedure or surgery | Ibrutinib Without Corticosteroids |
Primary outcome
Fraction of Participants With an Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Reported With an 80% Confidence Interval at 6 Months
Time frame: At 6 months
To evaluate the efficacy of Ibrutinib as a first-line treatment for persons with newly diagnosed chronic graft-versus-host disease (GvHD) overall response rate was measured using the 2014 National Institutes of Health (NIH) consensus criteria and reported with an 80% confidence interval. CR is defined as complete resolution in all of signs and symptoms at all affected organs or tissues. PR is defined as improvement in ≥1 organ or tissue with no progression in any other affected organ or tissue.
Fraction of Participants With an Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Reported With an 95% Confidence Interval at 6 Months
Time frame: At 6 months
To evaluate the efficacy of Ibrutinib as a first-line treatment for persons with newly diagnosed chronic graft-versus-host disease (GvHD) overall response rate was measured using the 2014 National Institutes of Health (NIH) consensus criteria and reported with a 95% confidence interval. CR is defined as complete resolution in all of signs and symptoms at all affected organs or tissues. PR is defined as improvement in ≥1 organ or tissue with no progression in any other affected organ or tissue.
3 secondary outcomes
Fraction of Grade 3 and Grade 4 Serious and/or Non-serious Adverse Events in Participants With Newly Diagnosed Chronic Graft-versus-host Disease (GvHD)
Time frame: Adverse events are captured from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the participant received the last study drug administration.
Failure-free Survival (FFS)
Time frame: Participants were followed from enrollment without death, relapse or new GVHD treatment up to 14 months
Fraction of Participants Alive at 24 Months Follow-up Post-treatment
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Z Pavletic, M.D. principal investigator
National Cancer Institute (NCI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib, ECG and PFT's in people with Chronic GVHD, run by National Cancer Institute (NCI) at 2 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 14 inclusion and 21 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 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 phase mean?
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 22 Jan 2025). 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?
Fraction of Participants With an Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Reported With an 80% Confidence Interval at 6 Months (time frame: At 6 months). 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?
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 23 Jan 2026; AzTrials last refreshed its copy on 7 Nov 2026.