Activated B-cell Diffuse Large B-Cell Lymphoma (ABC DLBCL)
Conditions
Keywords
de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, de Novo Activated B-cell (ABC), de Novo Activated B-cell, ABC DLBCL, DLBCL, Lymphoma, B-Cell, Immunoproliferative Disorders, Immune System Diseases, Bruton's tyrosine kinase
Brief summary
To characterize the safety profile of acalabrutinib in subjects with relapsed or refractory de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL).
Interventions
DRUGAcalabrutinib
Sponsors
Acerta Pharma BV
Study design
Allocation
NON_RANDOMIZED
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 de novo ABC DLBCL * Relapsed or refractory disease * Subjects must have ≥ 1 measurable disease sites
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 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 LVEF \< 50% * 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 |
|---|---|---|
| Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL. | SAEs collected from time of consent; TEAEs beginning after first dose and continuing through 30 days (+/- 7 days) after last dose. | Safety assessments included SAEs TEAEs, including AEs leading to discontinuation of study drug or dose reduction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration (AUC) | 1 Cycle (28 days) | To Characterize the Pharmacokinetic parameter AUC of acalabrutinib |
| Maximum Observed Plasma Concentration (Cmax) | 1 Cycle (28 days) | To Characterize the Pharmacokinetic parameter Cmax of acalabrutinib |
| Evaluate Pharmacodynamic (PD) Effects (Done at US Sites Only) | 2 Cycles (1 cycle = 28 days) and at end of treatment | To evaluate the concentration pharmacodynamic effects of acalabrutinib |
| Evaluate Activity of Acalabrutinib as Measured by Overall Response Rate (ORR) | From enrollment to the date of disease progression, assessed up to Cycle 48 (1 cycle is 28 days) | To evaluate the activity of acalabrutinib as measured by ORR |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - Relapse Subjects Acalabrutinib 100mg administered orally (PO) twice daily (BID) | 11 |
| Cohort 2 - Refractory Subjects Acalabrutinib 100mg administered orally (PO) twice daily (BID) | 10 |
| Total | 21 |
Baseline characteristics
| Characteristic | Cohort 1 - Relapse Subjects | Total | Cohort 2 - Refractory Subjects |
|---|---|---|---|
| Age, Continuous | 70.7 Year STANDARD_DEVIATION 9.57 | 64.1 Year STANDARD_DEVIATION 14.66 | 56.9 Year STANDARD_DEVIATION 16.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 19 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 10 Participants | 15 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 2 Participants | 6 Participants | 4 Participants |
| Region of Enrollment United States | 9 Participants | 15 Participants | 6 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 11 | 5 / 10 |
| other Total, other adverse events | 10 / 11 | 10 / 10 |
| serious Total, serious adverse events | 4 / 11 | 5 / 10 |
Outcome results
Primary
Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL.
Safety assessments included SAEs TEAEs, including AEs leading to discontinuation of study drug or dose reduction.
Time frame: SAEs collected from time of consent; TEAEs beginning after first dose and continuing through 30 days (+/- 7 days) after last dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - Relapse Subjects | Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL. | 3 Participants |
| Cohort 2 - Refractory Subjects | Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL. | 2 Participants |
Secondary
Area Under the Plasma Concentration (AUC)
To Characterize the Pharmacokinetic parameter AUC of acalabrutinib
Time frame: 1 Cycle (28 days)
Secondary
Evaluate Activity of Acalabrutinib as Measured by Overall Response Rate (ORR)
To evaluate the activity of acalabrutinib as measured by ORR
Time frame: From enrollment to the date of disease progression, assessed up to Cycle 48 (1 cycle is 28 days)
Secondary
Evaluate Pharmacodynamic (PD) Effects (Done at US Sites Only)
To evaluate the concentration pharmacodynamic effects of acalabrutinib
Time frame: 2 Cycles (1 cycle = 28 days) and at end of treatment
Secondary
Maximum Observed Plasma Concentration (Cmax)
To Characterize the Pharmacokinetic parameter Cmax of acalabrutinib
Time frame: 1 Cycle (28 days)