This phase II trial tests how well ibrutinib works in preventing chronic graft-versus-host disease (GVHD) in patients undergoing donor (allogeneic) hematopoietic cell transplantation (HCT). An allogeneic hematopoietic cell transplantation (allo-HCT) is a treatment in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical donor. When healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets. However, sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). Giving ibrutinib after the transplant may stop that from happening. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking a protein in the blood called Bruton's tyrosine kinase (BTK). By blocking BTK, ibrutinib inhibits certain immune cells that play a role in cGVHD. Giving ibrutinib after an allo-HCT may prevent the development of chronic GVHD.
PRIMARY OBJECTIVE: I. To evaluate the efficacy of ibrutinib in reducing the incidence of National Institutes of Health (NIH) moderate/severe chronic GVHD by 1-year post-registration. (Phase II Trial) SECONDARY OBJECTIVES: I. To determine the safety of ibrutinib when prescribed as prophylaxis for chronic GVHD. II. To determine the cumulative incidence of non-relapse mortality (NRM). III. To determine the cumulative incidence of relapse (CIR). IV. To determine the cumulative incidence of chronic GVHD (moderate/severe and all grades). V. To determine the cumulative incidence of late acute GVHD (LA GVHD). VI. To determine 1-year overall survival (OS) from time of transplantation. VII. To determine NIH moderate/severe chronic GVHD and relapse free survival (CRFS). VIII. To determine immune suppressive therapy required for therapy of chronic GVHD. IX. To determine the cumulative incidence of complete immune suppression (IS) discontinuation. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-30 of each cycle. Cycles repeat every 30 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo an echocardiography prior to registration on study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
40
Undergo echocardiography
Given PO
Mayo Clinic in Florida
Jacksonville, Florida, United States
RECRUITINGCumulative incidence of NIH moderate/severe chronic graft-versus-host disease (GVHD)
The cumulative incidence of National Institutes of Health (NIH) moderate/severe chronic GVHD will be estimated from the date of registration using a competing risk model, with death and relapse without NIH moderate/severe chronic GVHD as the competing risks.
Time frame: At 1 year post registration
Cumulative incidence of non-relapse mortality (NRM)
The cumulative incidence of NRM will be estimated from the date of registration using the competing risk model, with relapse as a competing risk event.
Time frame: Up to 1 year after last dose of study drug
Cumulative incidence of relapse
The cumulative incidence of relapse will be estimated from date of registration until date of relapse using the competing risk model with NRM as a competing risk event.
Time frame: Up to 1 year after last dose of study drug
Cumulative incidence of moderate/severe chronic GVHD
The cumulative incidence of moderate/severe chronic GVHD will be estimated from date of registration until date of first evidence of moderate/severe chronic GVHD using competing risk model, with relapse and death as competing risk events.
Time frame: Up to 1 year after last dose of study drug
Cumulative incidence of moderate/severe chronic GVHD
The cumulative incidence of moderate/severe chronic GVHD assessed from transplant up to 1 year post-transplant will be estimated.
Time frame: Up to 1 year after last dose of study drug
Cumulative incidence of chronic GVHD of all grades
The cumulative incidence of all grades of chronic GVHD will be estimated using the competing risk model, with relapse and death as competing risk events.
Time frame: Up to 1 year after last dose of study drug
Cumulative incidence of late acute GVHD
The cumulative incidence of acute GVHD will be estimated using the competing risk model, with relapse and death as competing risk events.
Time frame: Up to 1 year after last dose of study drug
Overall survival (OS)
OS is defined as the time from treatment to death, regardless of disease recurrence.
Time frame: Up to 1 year after last dose of study drug
NIH moderate/severe GVHD and relapse free survival (CRFS)
NIH moderate/severe CRFS is defined as the time from registration until moderate/severe chronic GVHD, relapse, or death due to any cause.
Time frame: Up to 1 year after last dose of study drug
Type and duration of immune suppressive therapy
The type and duration of immune suppressive therapy required for therapy of chronic GVHD will be summarized and described descriptively.
Time frame: Up to 1 year after last dose of study drug
Cumulative incidence of complete immune suppression (IS) discontinuation
The cumulative incidence of complete IS discontinuation will be estimated from the date of registration until the date of discontinuation of IS.
Time frame: Up to 1 year after last dose of study drug
Incidence of adverse events (AE)
The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns.
Time frame: Up to 1 year after last dose of study drug
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