A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy

January 23, 2024 updated by: Acerta Pharma BV

A Phase 2 Study of the Efficacy and Safety of ACP-196 in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy

A Phase 2 Study to evaluate the Efficacy and Safety of ACP-196 (acalabrutinib) in Subjects with Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

A Multicenter, Open-Label, Phase 2 study evaluating the efficacy and safety of Acalabrutinib in subjects with relapsed/refractory CLL (N=60) who are intolerant of ibrutinib therapy.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brugge, Belgium, 8000
        • Research Site
  • France
      • Bordeaux, France, 33076, FR
        • Research Site
  • Israel
      • Haifa, Israel, 31000
        • Research Site
  • Spain
      • Madrid, Spain, 28006
        • Research Site
  • United Kingdom
      • Bournemouth, United Kingdom, BH7 7DW
        • Research Site
      • Leeds, United Kingdom, LS9 7TF
        • Research Site
      • Manchester, United Kingdom, M20 4BX
        • Research Site
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85704
        • Research Site
    • California
      • Concord, California, United States, 94520
        • Research Site
      • La Jolla, California, United States, 92093
        • Research Site
      • Palo Alto, California, United States, 94304
        • Research Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Research Site
    • New York
      • Lake Success, New York, United States, 11042
        • Research Site
      • New York, New York, United States, 10021
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site
      • Sherman, Texas, United States, USA
        • Research Site
    • Washington
      • Seattle, Washington, United States, 98122
        • Research Site
      • Seattle, Washington, United States, 98108
        • Research Site
      • Spokane, Washington, United States, 99208
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Men and women ≥ 18 years of age.
  2. Prior diagnosis of CLL
  3. Must have received ≥ 1 prior therapy for CLL
  4. Intolerant of ibrutinib
  5. Documented disease progression after stopping ibrutinib therapy as defined by the IWCLL 2008 criteria
  6. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
  7. ECOG performance status of ≤ 2.

Exclusion Criteria:

  1. Ongoing AE attributed to ibrutinib therapy
  2. Treatment with systemic anticancer therapy for CLL is prohibited between discontinuation of ibrutinib and enrollment on this trial.
  3. Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT- 199)
  4. Prior malignancy (other than CLL), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the subject has been disease free for ≥ 2 years.
  5. Significant cardiovascular disease such as uncontrolled or symptomatic untreated 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, or QTc > 480 msec at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
  6. Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
  7. Evidence of active Richter's transformation or any evidence of disease progression on ibrutinib therapy or any BTK inhibitor.
  8. CNS involvement by CLL or related Richter's transformation.
  9. Known history of human immunodeficiency virus (HIV), serologic status reflecting active hepatitis B or C infection, or any uncontrolled active systemic infection.
  10. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
  11. History of stroke or intracranial hemorrhage within 2 months before the first dose of study drug.
  12. History of bleeding diathesis.
  13. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
  14. Major surgical procedure within 28 days of first dose of study drug.
  15. Requires treatment with a strong CYP3A inhibitor

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ACP-196 (acalabrutinib)
ACP-196 (acalabrutinib) 100 mg to be administered orally (PO) twice a day BID
Drug: ACP-196 (acalabrutinib)
ACP-196 100 mg to be administered orally (PO) twice a day BID.
Other Names:
  • Acalabrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib)
Time Frame: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 4 years and 7 months). 1 cycle = 28 days

The overall response rate (ORR) of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.

ORR is defined as the proportion of subjects achieving a best overall response (BOR) of either complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) at or before initiation of subsequent anticancer therapy. ORR will be analyzed per investigator's assessment.
From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 4 years and 7 months). 1 cycle = 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).

The progression-free survival of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.

PFS is calculated as date of disease progression or death (censoring date for censored subjects) - first dose date + 1.
From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).
Duration of Response
Time Frame: From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)

The duration of response of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.

DOR is calculated as date of disease progression or death (censoring date for censored subjects) - date of achieving the first CR, CRi, nPR, or PR + 1.
From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)
Time-to-Next Treatment
Time Frame: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)

The time to next treatment of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.

TTNT is defined as the time from date of first acalabrutinib treatment to date of institution of subsequent anticancer therapy for CLL or death due to any cause, whichever comes first. Subjects who do not have the above specified events prior to the data cutoff date will be censored at the date of last visit. TTNT will be calculated as follows:

(Earlier date of institution of subsequent anticancer therapy for CLL or date of death due to any cause) - date of first dose + 1. For censored subjects, date of last visit will replace earlier date of use of subsequent anticancer therapy for CLL or date of death due to any cause in the calculation.
From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)
Overall Survival
Time Frame: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).
The overall survival of ACP-319 (acalabrutinib) in subjects with relapsed/refractory CLL who are intolerant of ibrutinib therapy
From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Acerta Pharma BV

Investigators

  • Study Director: Acerta Clinical Trials, 1-888-292-9613; acertamc@dlss.com

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 8, 2016

Primary Completion (Actual)

October 16, 2020

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

March 11, 2016

First Submitted That Met QC Criteria

March 18, 2016

First Posted (Estimated)

March 24, 2016

Study Record Updates

Last Update Posted (Actual)

January 24, 2024

Last Update Submitted That Met QC Criteria

January 23, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACE-CL-208
  • 2015-005317-68 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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 register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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