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Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Acalabrutinib
Questionnaire Administration
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Moderate-Severe Chronic Graft Versus Host Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Moffitt Cancer CenterRecruiting
  • Roswell Park Comprehensive Cancer Center
  • The Ohio State University Wexner Medical CenterRecruiting
  • Vanderbilt University Medical CenterRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • Fred Hutch/University of Washington Cancer ConsortiumRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (acalabrutinib)

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Duration of response (DOR)
Will be described for the group achieving at least a PR, defined as the number of weeks the subject maintains a PR or CR. 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.
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).
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).
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.
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).

Full Information

First Posted
December 5, 2019
Last Updated
April 21, 2023
Sponsor
Fred Hutchinson Cancer Center
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT04198922
Brief Title
Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease
Official Title
Acalabrutinib for Chronic Graft-Versus-Host Disease
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 12, 2020 (Actual)
Primary Completion Date
January 31, 2025 (Anticipated)
Study Completion Date
January 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Moderate-Severe Chronic Graft Versus Host Disease, Hematopoietic and Lymphoid Cell Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (acalabrutinib)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib
Other Intervention Name(s)
1420477-60-6, ACP-196, Benzamide, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Best response (complete and partial response [CR + PR])
Description
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.
Time Frame
Within the first 6 months of treatment when the best response rate is known for each patient
Secondary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Description
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.
Time Frame
Up to 30 days following the last dose of acalabrutinib
Title
Duration of response (DOR)
Description
Will be described for the group achieving at least a PR, defined as the number of weeks the subject maintains a PR or CR. 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.
Time Frame
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
Title
Change in patient-reported outcomes: Lee Chronic GVHD Symptom Scale score
Description
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).
Time Frame
Baseline up to 3 years
Title
Change in patient-reported outcomes: Patient-Reported Outcomes Measurement Information System-29
Description
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).
Time Frame
Baseline up to 3 years
Title
Failure-free survival
Description
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.
Time Frame
At 6 months and 1 year
Title
Organ-specific response rates
Description
Response rates by organ will also be calculated and reported as ORR (CR+PR) versus all other categories (SD, PD, MR).
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Fatland
Phone
206.667.6830
Email
chronicGVHDstudies@fredhutch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephanie Lee
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Pidala
Phone
813-745-2556
Email
joseph.pidala@moffitt.org
First Name & Middle Initial & Last Name & Degree
Joseph Pidala, MD, PhD
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maurice Austin
Phone
614-929-9526
Email
Maurice.Austin@osumc.edu
First Name & Middle Initial & Last Name & Degree
Hannah K. Choe, MD
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carrie Kitko
Phone
615-936-1762
Email
carrie.l.kitko@vumc.edu
First Name & Middle Initial & Last Name & Degree
Carrie Kitko, MD
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna E. Kratz
Phone
855-220-4587
Email
aekratz@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Rohtesh Mehta, MD, MPH, MS
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Fatland
Phone
206-667-6830
Email
chronicGVHDstudies@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Stephanie Lee, MD, MPH

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Acalabrutinib for the Treatment of Chronic Graft Versus Host Disease

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