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Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease

Trial Status: Active

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.

Inclusion Criteria

  • 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
  • Presence of at least one of these manifestations: skin erythema, mouth sensitivity or ulcers, nausea, diarrhea or liver dysfunction attributable to chronic GVHD
  • 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
  • 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
  • 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
  • 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 or receiving therapeutic anti-platelet or anticoagulation, including warfarin or equivalent vitamin K antagonist
  • Prothrombin time/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of lupus anticoagulant) > 2 x upper limit of normal (ULN)
  • Requires treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study
  • 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 28 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
  • 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
  • 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
  • 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


Moffitt Cancer Center
Contact: Joseph Pidala
Phone: 813-745-2556

New York

Roswell Park Cancer Institute
Status: ACTIVE
Contact: George Liwei Chen
Phone: 716-845-8722


Vanderbilt University / Ingram Cancer Center
Contact: Carrie Lynn Kitko
Phone: 615-936-1762


Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE
Contact: Ahona Mukherjee
Phone: 206-667-6830


I. Determine the best overall response rate to acalabrutinib in patients who require second or later line therapy for chronic graft versus host disease (GVHD).


I. Describe the safety and tolerability of acalabrutinib in the chronic GVHD population.

II. Determine the duration of response, among patients achieving a complete or partial response.

III. Determine the change in patient-reported outcomes, specifically the Lee Chronic (c) GVHD Symptom Scale score and the Patient-Reported Outcomes Measurement Information System (PROMIS)-29, between enrollment and follow-up.

IV. Determine the failure-free survival (FFS) (duration of relapse-free survival without adding another systemic treatment for chronic GVHD).

V. Determine organ-specific response rates.

VI. Store peripheral blood mononuclear cells and plasma for future biologic studies.


Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 6 cycles with an option to continue for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then periodically thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Fred Hutch / University of Washington Cancer Consortium

Principal Investigator
Stephanie Joi Lee

  • Primary ID RG1006135
  • Secondary IDs NCI-2019-06980, 8801
  • ID NCT04198922