Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease

Acalabrutinib for Chronic Graft-Versus-Host Disease

Sponsors

Lead Sponsor: Fred Hutchinson Cancer Research Center

Collaborator: AstraZeneca

Source Fred Hutchinson Cancer Research Center
Brief Summary

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.

Detailed Description

OUTLINE: 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.

Overall Status Recruiting
Start Date 2020-12-12
Completion Date 2025-01-31
Primary Completion Date 2023-01-31
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Best response (complete and partial response [CR + PR]) Within the first 6 months of treatment when the best response rate is known for each patient
Secondary Outcome
Measure Time Frame
Incidence of adverse events (AEs) Up to 30 days following the last dose of acalabrutinib
Duration of response (DOR) From the date the PR is documented until loss of the response or start of another systemic immunosuppressive treatment for chronic graft versus host disease (GVHD), whichever occurs first, assessed up to 3 years
Change in patient-reported outcomes: Lee Chronic GVHD Symptom Scale score Baseline up to 3 years
Change in patient-reported outcomes: Patient-Reported Outcomes Measurement Information System-29 Baseline up to 3 years
Failure-free survival At 6 months and 1 year
Organ-specific response rates Up to 3 years
Enrollment 50
Condition
Intervention

Intervention Type: Drug

Intervention Name: Acalabrutinib

Description: Given PO

Arm Group Label: Treatment (acalabrutinib)

Intervention Type: Other

Intervention Name: Questionnaire Administration

Description: Ancillary studies

Arm Group Label: Treatment (acalabrutinib)

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Stephanie Lee Principal Investigator Fred Hutch/University of Washington Cancer Consortium
Overall Contact

Last Name: Peter Fatland

Phone: 206.667.6830

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
Moffitt Cancer Center | Tampa, Florida, 33612, United States Not yet recruiting Joseph Pidala 813-745-2556 [email protected] Joseph Pidala Principal Investigator
Roswell Park Comprehensive Cancer Center | Buffalo, New York, 14203, United States Recruiting George Chen 716-845-8722 [email protected] George Chen Principal Investigator
Vanderbilt University Medical Center | Nashville, Tennessee, 37212, United States Not yet recruiting Carrie Kitko 615-936-1762 [email protected] Carrie Kitko Principal Investigator
Fred Hutch/University of Washington Cancer Consortium | Seattle, Washington, 98109, United States Recruiting Peter Fatland 206-667-6830 [email protected] Stephanie Lee Principal Investigator
Location Countries

United States

Verification Date

2021-10-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Treatment (acalabrutinib)

Type: Experimental

Description: Patients receive acalabrutinib 100 mg PO 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.

Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News