NCT04294641

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

Type	Name	Description
DRUG	Ibrutinib	140 mg capsules for a dose of 420 mg daily by mouth for up to 12 months.
DIAGNOSTIC_TEST	ECG	At screening.
DIAGNOSTIC_TEST	PFT's	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).
DIAGNOSTIC_TEST	CT	Non-contrast CT at baseline and later during the study if clinically indicated.
DRUG	Steroid pulse (prednisone)	0.5-2mg/kg/day allowed for clinical disease stabilization during first 4 weeks after starting Ibrutinib.
DRUG	Voriconazole	At any dose.
DRUG	Posaconazole	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..
DRUG	Azithromycin	Treat or prevent bronchiolitis obliterans.
DRUG	Montelukast	Treat or prevent bronchiolitis obliterans.
DRUG	Budesonide	Treat or prevent gastrointestinal acute graft-versus host disease (GvHD).
DRUG	Beclomethasone	Treat or prevent gastrointestinal acute graft-versus host disease (GvHD).
OTHER	Filgrastim	Neutrophil growth factor permitted per institutional policy
OTHER	Pegfilgrastim	Neutrophil growth factor permitted per institutional policy.
OTHER	Erythropoietin	Red cell growth factor permitted per institutional policy.
OTHER	Transfusions	According to institutional policy.
PROCEDURE	Oral/Skin biopsy	Optional. Baseline, Cycle 7, Day 1 (6 months), Cycle 12, Day 28 (12 months) and Cycle 24, Day 28.

Timeline

• Start date: 2021-05-10
• Primary completion: 2024-06-24
• Completion: 2024-10-01
• First posted: 2020-03-04
• Last updated: 2026-01-23
• Results posted: 2025-01-22

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study