Front Line Ibrutinib Without Corticosteroids for Newly Diagnosed Chronic Graft-versus-Host Disease

NCT04294641 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 20005820-C-0058
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Chronic GVHD

Keywords

Immunosuppressive Therapy; Kinase Inhibitors; steroid pulses; Hematologic Malignancies; alloHSCT

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  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)

  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

  24 months

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Adverse events are collected from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the participant received the last study drug administration.

Study Arms (1)

Ibrutinib Without Corticosteroids

EXPERIMENTAL

Determine response rate via continuous daily dose by mouth to determine efficacy

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

Interventions

Ibrutinib DRUG

140 mg capsules for a dose of 420 mg daily by mouth for up to 12 months.

Also known as: Imbruvica

Ibrutinib Without Corticosteroids

ECG DIAGNOSTIC_TEST

At screening.

Also known as: Electrocardiogram

Ibrutinib Without Corticosteroids

PFT's DIAGNOSTIC_TEST

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).

Also known as: Pulmonary function tests

Ibrutinib Without Corticosteroids

CT DIAGNOSTIC_TEST

Non-contrast CT at baseline and later during the study if clinically indicated.

Also known as: Computed tomography

Ibrutinib Without Corticosteroids

Steroid pulse (prednisone) DRUG

0.5-2mg/kg/day allowed for clinical disease stabilization during first 4 weeks after starting Ibrutinib.

Also known as: Rayos, Prednisone Intensol, Deltasone

Ibrutinib Without Corticosteroids

Voriconazole DRUG

At any dose.

Also known as: Vfend, Vfend IV

Ibrutinib Without Corticosteroids

Posaconazole DRUG

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..

Also known as: Noxafil

Ibrutinib Without Corticosteroids

Azithromycin DRUG

Treat or prevent bronchiolitis obliterans.

Also known as: AzaSite, Zithromax, Zithromax Z-Pak

Ibrutinib Without Corticosteroids

Montelukast DRUG

Treat or prevent bronchiolitis obliterans.

Also known as: Singulair

Ibrutinib Without Corticosteroids

Budesonide DRUG

Treat or prevent gastrointestinal acute graft-versus host disease (GvHD).

Also known as: Entocort, Uceris, Rhinocort Allergy

Ibrutinib Without Corticosteroids

Beclomethasone DRUG

Treat or prevent gastrointestinal acute graft-versus host disease (GvHD).

Also known as: Beclometasone, beclomethasone dipropionate, Qvar

Ibrutinib Without Corticosteroids

Filgrastim OTHER

Neutrophil growth factor permitted per institutional policy

Also known as: Neupogen

Ibrutinib Without Corticosteroids

Pegfilgrastim OTHER

Neutrophil growth factor permitted per institutional policy.

Also known as: Neulasta

Ibrutinib Without Corticosteroids

Erythropoietin OTHER

Red cell growth factor permitted per institutional policy.

Also known as: haematopoietin, haemopoietin

Ibrutinib Without Corticosteroids

Transfusions OTHER

According to institutional policy.

Ibrutinib Without Corticosteroids

Oral/Skin biopsy PROCEDURE

Optional. Baseline, Cycle 7, Day 1 (6 months), Cycle 12, Day 28 (12 months) and Cycle 24, Day 28.

Ibrutinib Without Corticosteroids

Eligibility Criteria

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

You may qualify if:

• 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%.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Washington University, School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Hematologic Neoplasms

Interventions

ibrutinib; Electrocardiography; Respiratory Function Tests; Tomography, X-Ray Computed; Prednisone; Voriconazole; posaconazole; Azithromycin; montelukast; Budesonide; Beclomethasone; Filgrastim; pegfilgrastim; Erythropoietin; Blood Transfusion

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Diagnostic Techniques, Respiratory System; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Pregnenediones; Pregnenes; Pregnadienetriols; Steroids, Chlorinated; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Biological Therapy; Therapeutics

Results Point of Contact

• Title: Dr. James Gulley
• Organization: National Cancer Institute

gulleyj@mail.nih.gov

301-480-8870

Study Officials

• Steven Z Pavletic, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 4, 2020
• Study Start: May 10, 2021
• Primary Completion: June 24, 2024
• Study Completion: October 1, 2024
• Last Updated: January 23, 2026
• Results First Posted: January 22, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (2)