Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease

NCT04198922 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1006135NCI-2019-069808801
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

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.

Conditions

Recurrent Moderate-Severe Chronic Graft Versus Host Disease; Hematopoietic and Lymphoid Cell Neoplasm

Outcome Measures

Primary Outcomes (1)

• Best response (complete and partial response [CR + PR])

  The composite outcome of CR and PR, calculated according to the proposed response definitions of the 2014 National Institutes of Health Consensus Conference. Exact 95% confidence intervals (CI) will be calculated for the objective response rate using the Clopper and Pearson method. Will also compare the observed best ORR with the published efficacy of ibrutinib (67%) and provide the 95% CI for the difference.

  Within the first 6 months of treatment when the best response rate is known for each patient

Secondary Outcomes (6)

• 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

Study Arms (1)

Treatment (acalabrutinib)

EXPERIMENTAL

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.

Drug: Acalabrutinib; Other: Questionnaire Administration

Interventions

Acalabrutinib DRUG

Given PO

Also known as: 1420477-60-6, ACP-196, Benzamide, Bruton Tyrosine Kinase Inhibitor ACP-196

Treatment (acalabrutinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (acalabrutinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (6)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

acalabrutinib; benzamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Stephanie Lee, MD, MPH

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 13, 2019
• Study Start: December 11, 2020
• Primary Completion: September 29, 2025
• Study Completion (Estimated): April 30, 2027
• Last Updated: November 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)