A Phase II Study of Ibrutinib as Prophylaxis for Chronic Graft-Versus-Host Disease (GVHD) in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation (Allo-HCT)
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.
• 50 to 110 days post-transplant prior to registration
• Age ≥ 18 years
• HLA matched-related, matched unrelated donors (defined as 8/8 \[class I: HLA A, B, C, and class II: DRB1\]), or HLA-mismatched-unrelated donors (defined as 7/8 \[with single mismatch at class I: HLA A, B, C, or class II: DRB1\])
• Karnofsky performance status (PS) ≥ 70
• Hemoglobin ≥ 8.0 g/dL (untransfused) (obtained ≤ 7 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1000/mm\^3 (without growth factor support) (obtained ≤ 7 days prior to registration)
• Platelet count ≥ 50,000/mm\^3 (untransfused) (obtained ≤ 7 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 7 days prior to registration)
• Total bilirubin ≤ 1.5 x ULN (unless it is due to Gilbert's syndrome or causes other than liver) OR alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2 x ULN (unless it is due to Gilbert's syndrome or causes other than liver) (obtained ≤ 7 days prior to registration)
• Calculated creatinine clearance ≥ 40 ml/min using the Cockcroft-Gault formula (obtained ≤ 7 days prior to registration)
• Adequate cardiac and pulmonary function at baseline (may be based on pre-transplant vital organ work up):
‣ Cardiac evaluation to determine left ventricular ejection fraction (LV-EF) if there is any clinical reason (for example an ischemic event or hypovolemic shock) to suspect that the LV-EF was affected from the time of the prior measurement of baseline (required ≥ 45%)
⁃ Pulmonary evaluation to determine adequate pulmonary function with a diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 50% predicted value, forced expiratory volume in 1 second (FEV1) ≥ 50% predicted value and forced vital capacity (FVC) ≥ 50% predicted value
• Persons of childbearing potential must have negative serum pregnancy test ≤ 7 days prior to registration. Persons of non-reproductive potential are defined as follows: post-menopausal by history - no menses for ≥ 1 year; or status post (s/p) hysterectomy; or s/p bilateral tubal ligation; or history of bilateral oophorectomy
• All subjects agreeable to using both a highly effective method of birth control \[for example, implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), or sterilized partner\] and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug
• Provide written informed consent
• Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study).
‣ Note: During the active monitoring phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up