Mantle Cell Lymphoma (MCL)
Conditions
Keywords
Bruton tyrosine kinase inhibitor, Btk, Mantle Cell Lymphoma, MCL, ACP-196, Acalabrutinib, ACE-LY-004, Calquence
Brief summary
The purpose of this study is to characterize the safety and efficacy profile of ACP-196 (acalabrutinib) in subjects with relapsed or refractory Mantle Cell Lymphoma (MCL).
Detailed description
This clinical trial is a Phase 2, multicenter, (approximately 70 global centers), open-label study in subjects with histologically documented MCL, who have relapsed after, or were refractory to, ≥ 1 (but not \> 5) prior treatment regimens. Subjects will be enrolled and will take 100 mg of acalabrutinib twice per day (BID) in repeated 28-day cycles. Treatment with acalabrutinib may be continued until disease progression or an unacceptable drug-related toxicity occurs. Dose modification provisions are provided in the study protocol. All subjects will have hematology, chemistry, and urinalysis safety panels done at screening. Once dosing commences (Day 1), all subjects will be evaluated for safety, including serum chemistry and hematology, once weekly for the first 4 weeks, every 2 weeks in Cycle 2, every 4 weeks in Cycles 3 to 12, and every 24 weeks thereafter. PK/PD testing will be done in Cycles 1 and 2. Tumor assessments will be completed at 8- to 24-week intervals during the trial.
Interventions
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
* Men and women ≥ 18 years of age. * Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. * Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.
Exclusion criteria
* A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ACP-196 (acalabrutinib), or put the study outcomes at undue risk * 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, or corrected QT interval (QTc) \> 480 msec. * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. * Breast feeding or pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL. | From the date of the first dose until 30 days after the last dose of the study drug or start of a new anti-cancer treatment, whichever came first, assessed up to approximately 4 year and 10 months. 1 cycle =28 days | The overall response rate (ORR) is defined as the proportion of subjects achieving either a partial remission (response) (PR) or complete response (CR) according to the Lugano Classification for NHL (Cheson 2014) as assessed by investigators, where SD stands for Stable Disease, PD for Progressive Disease and NE for Not Evaluable. |
Countries
Australia, Belgium, Czechia, France, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORAcerta Pharma
1-888-292-9613
Participant flow
Pre-assignment details
For the ACE-LY-004 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. No further data collection for analysis and reporting will be completed after the final Analysis.
Participants by arm
| Arm | Count |
|---|---|
| ACP-196 100 mg BID subjects with relapsed/refractory MCL | 124 |
| Total | 124 |
Baseline characteristics
| Characteristic | ACP-196 100 mg BID |
|---|---|
| Age, Continuous | 67.1 Years STANDARD_DEVIATION 10.5 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 90 Participants |
| Race/Ethnicity, Customized Not Reported | 29 Participants |
| Race/Ethnicity, Customized White | 92 Participants |
| Region of Enrollment Australia | 2 Participants |
| Region of Enrollment Belgium | 2 Participants |
| Region of Enrollment France | 26 Participants |
| Region of Enrollment Italy | 8 Participants |
| Region of Enrollment Netherlands | 5 Participants |
| Region of Enrollment Poland | 19 Participants |
| Region of Enrollment Spain | 4 Participants |
| Region of Enrollment United Kingdom | 13 Participants |
| Region of Enrollment USA | 45 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 59 / 124 |
| other Total, other adverse events | 122 / 124 |
| serious Total, serious adverse events | 62 / 124 |
Outcome results
Primary
Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL.
The overall response rate (ORR) is defined as the proportion of subjects achieving either a partial remission (response) (PR) or complete response (CR) according to the Lugano Classification for NHL (Cheson 2014) as assessed by investigators, where SD stands for Stable Disease, PD for Progressive Disease and NE for Not Evaluable.
Time frame: From the date of the first dose until 30 days after the last dose of the study drug or start of a new anti-cancer treatment, whichever came first, assessed up to approximately 4 year and 10 months. 1 cycle =28 days
Population: The analysis population included all treated subjects.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ACP-196 (Acalabrutinib) | Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL. | CR | 59 Participants |
| ACP-196 (Acalabrutinib) | Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL. | PR | 42 Participants |
| ACP-196 (Acalabrutinib) | Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL. | SD | 10 Participants |
| ACP-196 (Acalabrutinib) | Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL. | PD | 10 Participants |
| ACP-196 (Acalabrutinib) | Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL. | NE | 3 Participants |