Recurrent Moderate-Severe Chronic Graft Versus Host DiseasePhase 2NCT04198922

Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease

A Phase 2 study testing Acalabrutinib and Questionnaire Administration in people with Recurrent Moderate-Severe Chronic Graft Versus Host Disease and Hematopoietic and Lymphoid Cell Neoplasm, run by Fred Hutchinson Cancer Center at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Recurrent Moderate-Severe Chronic Graft Versus Host Disease, Hematopoietic and Lymphoid Cell Neoplasm
What is being tested?: Acalabrutinib and Questionnaire Administration
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 6 sitesUnited States
Study dates: 11 Dec 2020to 30 Apr 2027
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

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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

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14203
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Moffitt Cancer Center
Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Acalabrutinib for Chronic Graft-Versus-Host Disease

Read the 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.

Conditions: Recurrent Moderate-Severe Chronic Graft Versus Host Disease, Hematopoietic and Lymphoid Cell Neoplasm
Being tested: Acalabrutinib, Questionnaire Administration
Medical subject headings: Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AcalabrutinibDrug
Also called 1420477-60-6, ACP-196, Benzamide, Bruton Tyrosine Kinase Inhibitor ACP-196
Given PO
Questionnaire AdministrationOther
Ancillary studies

Study groups in NCT04198922
Study group	Role	What they receive
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. Receives: Drug: Acalabrutinib; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

Best Response (Complete and Partial Response [CR + PR])
The composite outcome of Complete Response (CR) and Partial Response (PR), calculated according to the proposed therapeutic response in chronic graft-versus-host disease definitions of the 2014 National Institutes of Health Consensus Conference. The observed best Overall Response Rate (ORR) is also compared with the published efficacy of ibrutinib (67%) and the 95% CI for the difference presented.
Measured: Within 6 months of start of treatment

Secondary outcomes (6)

Incidence of Adverse Events (AEs)
Defined as grade 3 and above according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and all serious AEs (SAEs) described for the population receiving at least one dose of acalabrutinib at least from the time of consent through the safety follow-up period. Any AE/SAE at least possibly related to acalabrutinib therapy will be reported for the duration of the study.
Measured: Up to 30 days following the last dose of acalabrutinib
Duration of Response (DOR)
The median number of weeks a PR or better response (CR) is maintained, among the group achieving at least a PR, calculated from the date of the first response. Will be estimated using the Kaplan-Meier method. Approximate 95% CIs for median DOR will be computed using the formula proposed by Brookmeyer and Crowley.
Measured: 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
Will be assessed by the Lee Chronic GVHD Symptom Scale score. Scores will be calculated based on published algorithms with absolute changes and clinically meaningful changes described for the population as a whole and based on CR + PR versus stable disease (SD) + mixed response (MR) + progressive disease (PD).
Measured: Baseline up to 6 months
Change in Patient-reported Outcomes: Patient-Reported Outcomes Measurement Information System-29
Will be assessed by the Patient-Reported Outcomes Measurement Information System-29. Scores will be calculated based on published algorithms with absolute changes and clinically meaningful changes described for the population as a whole and based on CR + PR versus stable disease (SD) + mixed response (MR) + progressive disease (PD).
Measured: Baseline up to 6 months
Failure-free Survival
Will be defined as the duration of relapse-free survival without adding any other systemic treatment for chronic GVHD. Will be estimated with the composite event of death from any cause, relapse and addition of secondary immune suppressive agents using the Kaplan-Meier method. Systemic immune-suppressive agents include orally or intravenously administered systemically active immune-suppressive drugs, as well as procedures including extra-corporeal photopheresis.
Measured: At 6 months and 1 year
Organ-specific Response Rates
Response rates by organ will also be calculated and reported as ORR (CR+PR) versus all other categories (SD, PD, MR)
Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Dec 202030 Apr 2027

First posted13 Dec 2019
Study start11 Dec 2020
Primary completion29 Sep 2025
Study completion30 Apr 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Recurrent Moderate-Severe Chronic Graft Versus Host DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04198922
Sponsor's protocol ID: RG1006135
Other IDs: NCI-2019-06980, 8801
Status last verified: Sep 2026
First submitted: 5 Dec 2019
Last updated: 14 Oct 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No