Chronic Lymphocytic Leukemia
Conditions
Keywords
Chronic Lymphocytic Leukemia, Ibrutinib Intolerant
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.
Interventions
ACP-196 100 mg to be administered orally (PO) twice a day BID.
Sponsors
Acerta Pharma BV
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | 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. |
| Duration of Response | 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. |
| Time-to-Next Treatment | 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. |
| Overall Survival | 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 |
Countries
Belgium, France, Israel, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORAcerta Clinical Trials
1-888-292-9613; acertamc@dlss.com
Participant flow
Pre-assignment details
For the ACE-CL-208 program, Study Terminated by Sponsor refers to the following: Patients receiving treatment benefits will continue to be provided with study medication in the Post Final Analysis Management of the trial. Sponsor has terminated further data collection for analysis and reporting
Participants by arm
| Arm | Count |
|---|---|
| Acalabrutinib Acalabrutinib 100 mg BID | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Acalabrutinib |
|---|---|
| Age, Continuous | 69.2 Years STANDARD_DEVIATION 9.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 54 Participants |
| Race/Ethnicity, Customized Not Reported | 4 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 56 Participants |
| Region of Enrollment Europe | 11 Participants |
| Region of Enrollment United States | 49 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 60 |
| other Total, other adverse events | 60 / 60 |
| serious Total, serious adverse events | 32 / 60 |
Outcome results
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.
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
Population: All Treated Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acalabrutinib | The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) | 70.0 Percentage of participants |
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.
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)
Population: All Treated Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acalabrutinib | Duration of Response | NA Months |
Secondary
Overall Survival
The overall survival of ACP-319 (acalabrutinib) in subjects with relapsed/refractory CLL who are intolerant of ibrutinib therapy
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).
Population: All Treated Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acalabrutinib | Overall Survival | NA Months |
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.
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).
Population: All Treated Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acalabrutinib | Progression-Free Survival | NA Months |
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.
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)
Population: All Treated Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acalabrutinib | Time-to-Next Treatment | 44.0 Months |