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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02717611
• Other study ID #: ACE-CL-208
• Secondary ID: 2015-005317-68
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 8, 2016
• Est. completion date: September 1, 2026

Study information

• Verified date: April 2024
• Source: Acerta Pharma BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: September 1, 2026
• Est. primary completion date: October 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• ACP-196 (acalabrutinib)
ACP-196 100 mg to be administered orally (PO) twice a day BID.

Locations

Country	Name	City	State
Belgium	Research Site	Brugge
France	Research Site	Bordeaux
Israel	Research Site	Haifa
Spain	Research Site	Madrid
United Kingdom	Research Site	Bournemouth
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Manchester
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbus	Ohio
United States	Research Site	Concord	California
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Lake Success	New York
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Palo Alto	California
United States	Research Site	Seattle	Washington
United States	Research Site	Seattle	Washington
United States	Research Site	Sherman	Texas
United States	Research Site	Spokane	Washington
United States	Research Site	Tucson	Arizona
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Acerta Pharma BV

Countries where clinical trial is conducted

United States,  Belgium,  France,  Israel,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib)	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	Progression-Free Survival	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).
Secondary	Duration of Response	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)
Secondary	Time-to-Next Treatment	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)
Secondary	Overall Survival	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).

External Links

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