Clinical trial NCT02717611: A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
Ibrutinib Intolerant
Lead sponsor: Acerta Pharma BV
Sponsor class: INDUSTRY
First posted: 2016-03-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib)
timeFrame: 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 outcomes:
measure: Progression-Free Survival
timeFrame: 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).
measure: Duration of Response
timeFrame: 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)
measure: Time-to-Next Treatment
timeFrame: 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)
measure: Overall Survival
timeFrame: 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).
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Concord
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Palo Alto
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Lake Success
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Sherman
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Brugge
country: Belgium
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Bournemouth
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: 1-888-292-9613; acertamc@dlss.com
name: Acerta Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Rogers KA, Thompson PA, Allan JN, Coleman M, Sharman JP, Cheson BD, Jones D, Izumi R, Frigault MM, Quah C, Raman RK, Patel P, Wang MH, Kipps TJ. Phase II study of acalabrutinib in ibrutinib-intolerant patients with relapsed/refractory chronic lymphocytic leukemia. Haematologica. 2021 Sep 1;106(9):2364-2373. doi: 10.3324/haematol.2020.272500.
citation: Mato AR, Nabhan C, Barr PM, Ujjani CS, Hill BT, Lamanna N, Skarbnik AP, Howlett C, Pu JJ, Sehgal AR, Strelec LE, Vandegrift A, Fitzpatrick DM, Zent CS, Feldman T, Goy A, Claxton DF, Bachow SH, Kaur G, Svoboda J, Nasta SD, Porter D, Landsburg DJ, Schuster SJ, Cheson BD, Kiselev P, Evens AM. Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience. Blood. 2016 Nov 3;128(18):2199-2205. doi: 10.1182/blood-2016-05-716977. Epub 2016 Sep 6.