Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease
Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease
This phase II trial studies how well acalabrutinib works in treating patients with chronic graft versus host disease. Acalabrutinib may be an effective treatment for graft-versus-host disease caused by a stem cell transplant.
Miscellaneous
Phase II
Adults
Not Available
Not Available
Kitko, Carrie
National
Vanderbilt University
05-24-2022
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Men and women 18 years of age
Moderate-severe chronic GVHD, diagnosed per the 2014 National Institutes of Health (NIH) criteria
Progression or recurrence of active chronic GVHD signs/symptoms after treatment with steroids
Karnofsky performance status >= 70%
Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib
Men must refrain from sperm donation during the study
Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
Exclusion Criteria:
Hospitalization for evaluation or management of an infection within the last 8 weeks
Change in immunosuppressive regimen within the 2 weeks prior to enrollment
Noncompliance
Treatment of chronic GVHD with ibrutinib
Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug
Recurrent or prior malignancy (or any other malignancy that requires active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for >= 2 years
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study
Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
Received a live virus vaccination within 28 days of first dose of study drug
Known history of infection with human immunodeficiency virus (HIV)
Uncontrolled, active significant infection (e.g., bacterial, viral, fungal or progressive multifocal leukoencephalopathy)
Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components)
Active bleeding, history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
Requires warfarin or equivalent vitamin K antagonist
History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
Major surgical procedure within 30 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
Child-Pugh score of C for hepatic impairment
Total bilirubin > 2 mg/dL or alanine aminotransferase (ALT) > 2 x upper limit of normal, unless abnormalities are due to liver GVHD, in which case total bilirubin > 3 mg/dL or ALT 5 x upper limit of normal are exclusions
Absolute neutrophil count 1.0 x 10^9/L or use of myeloid growth factors within the past 2 weeks
Platelet count 50 x 10^9/L or platelet transfusion or thrombomimetic agent within the past 2 weeks
Glomerular filtration rate 50 mL/min/1.73 m^2
Breastfeeding or pregnant
Concurrent participation in another clinical trial and receiving a non-Food and Drug Administration (FDA) approved medication
Men and women 18 years of age
Moderate-severe chronic GVHD, diagnosed per the 2014 National Institutes of Health (NIH) criteria
Progression or recurrence of active chronic GVHD signs/symptoms after treatment with steroids
Karnofsky performance status >= 70%
Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib
Men must refrain from sperm donation during the study
Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
Exclusion Criteria:
Hospitalization for evaluation or management of an infection within the last 8 weeks
Change in immunosuppressive regimen within the 2 weeks prior to enrollment
Noncompliance
Treatment of chronic GVHD with ibrutinib
Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug
Recurrent or prior malignancy (or any other malignancy that requires active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for >= 2 years
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study
Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
Received a live virus vaccination within 28 days of first dose of study drug
Known history of infection with human immunodeficiency virus (HIV)
Uncontrolled, active significant infection (e.g., bacterial, viral, fungal or progressive multifocal leukoencephalopathy)
Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components)
Active bleeding, history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
Requires warfarin or equivalent vitamin K antagonist
History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
Major surgical procedure within 30 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
Child-Pugh score of C for hepatic impairment
Total bilirubin > 2 mg/dL or alanine aminotransferase (ALT) > 2 x upper limit of normal, unless abnormalities are due to liver GVHD, in which case total bilirubin > 3 mg/dL or ALT 5 x upper limit of normal are exclusions
Absolute neutrophil count 1.0 x 10^9/L or use of myeloid growth factors within the past 2 weeks
Platelet count 50 x 10^9/L or platelet transfusion or thrombomimetic agent within the past 2 weeks
Glomerular filtration rate 50 mL/min/1.73 m^2
Breastfeeding or pregnant
Concurrent participation in another clinical trial and receiving a non-Food and Drug Administration (FDA) approved medication
