Non Hodgkin Lymphoma
Conditions
Keywords
Bruton tyrosine kinase inhibitor, Btk, Follicular Lymphoma, FL, acalabrutinib, ACP-196, MZL, Marginal Zone Lymphoma
Brief summary
Part 1: To characterize the safety profile of acalabrutinib alone or in combination with rituximab in subjects with R/R FL. Part 2: To characterize the activity of acalabrutinib alone or in combination with rituximab in subjects with R/R MZL, as measured by ORR. Part 3: To characterize the safety of acalabrutinib in combination with rituximab and lenalidomide in subjects with R/R FL
Detailed description
An Open-label, Phase 1b/2 Study of Acalabrutinib Alone or in Combination Therapy in Subjects with B-cell Non-Hodgkin Lymphoma
Interventions
DRUGacalabrutinib
DRUGrituximab (IV)
DRUGLenalidomide
Sponsors
Acerta Pharma BV
AstraZeneca
Study design
Allocation
NA
Intervention model
PARALLEL
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. * Part 1: A confirmed diagnosis of FL Grade 1, 2, or 3a, which has relapsed after, or been refractory to ≥ 1 prior therapy for FL, or subjects who have not previously received systemic anticancer therapy for FL., and which requires treatment. * Part 2: For subject with relapsed or refractory MZL: Histologically confirmed MZL including splenic, nodal, and extranodal sub-types 1. Subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criterion #4; 2. Subjects with gastric mucosa-associated lymphoid tissue (MALT) lymphoma must be Helicobacter pylori (HP)-negative * Part 3: For subjects with FL: Pathologically confirmed diagnosis of FL Grade 1, 2, or 3a, which has relapsed after, or been refractory to ≥ 1 prior therapy for FL and which requires treatment per National Cancer Institute or ESMO clinical practice guidelines. * 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 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 Qtc \>480 msec * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. * Breast feeding or pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Incidence of Treatment-emergent Adverse Events. | From the first dose of study drug until study discontinuation, 30 days after the last dose of study drug or one day before the first subsequent anticancer therapy, whichever was earlier, up to 80.7 months (the maximum participant's time on this study). | Treatment-emergent adverse events were used to characterize the safety profile of acalabrutinib alone or in combination with rituximab in participants with relapsed/refractory follicular lymphoma (R/R FL). |
| Part 2: Investigator Assessed Objective Response Rate (ORR) According to the Lugano Classification for Non-Hodgkin Lymphoma (NHL). | Based on all response assessments since the first dose of study drug until study discontinuation or the initiation of subsequent anticancer therapy, whichever was earlier, up to 65.1 months (the maximum participant's time on this study). | The objective response rate (ORR) is used to characterize the activity of acalabrutinib alone or in combination with rituximab in participants with relapsed/refractory marginal zone lymphoma (R/R MZL). |
| Part 3: Incidence of Treatment-emergent Adverse Events. | From the first dose of study drug until study discontinuation, 30 days after the last dose of study drug or one day before the first subsequent anticancer therapy, whichever was earlier, up to 54.3 months (the maximum participant's time on this study). | Treatment-emergent adverse events were used to characterize the safety of acalabrutinib in combination with rituximab and lenalidomide in participants with relapsed/refractory follicular lymphoma (R/R FL). |
Countries
Canada, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| P1: RR Acalabrutinib 100 mg BID (Relapsed/Refractory Cohort: Acalabrutinib 100 mg Twice a Day (BID)) | 12 |
| P1: RR Acalabrutinib 100 mg BID + Rituximab (Relapsed/Refractory Cohort: Acalabrutinib 100 mg Twice a Day (BID) + Rituximab 375 mg/m2) | 13 |
| P1: RR Acalabrutinib 200 mg QD (Relapsed/Refractory Cohort: Acalabrutinib 200 mg once a day (QD)) | 2 |
| P1: TN Acalabrutinib 100 mg BID + Rituximab (Treatment Naive Cohort: Acalabrutinib 100 mg Twice a Day (BID) + Rituximab 375 mg/m2) | 13 |
| P2: Acalabrutinib (Acalabrutinib 100 mg Twice a Day (BID)) | 43 |
| P2: Acalabrutinib + Rituximab (Acalabrutinib 100 mg Twice a Day (BID) + Rituximab 375 mg/m2) | 1 |
| P3: Acalabrutinib + Rituximab + Lenalidomide 15 mg (Acalabrutinib 100 mg Twice a Day (BID) + Rituximab 375 mg/m2 + Lenalidomide 15 mg Daily (QD)) | 8 |
| P3: Acalabrutinib + Rituximab + Lenalidomide 20 mg (Acalabrutinib 100 mg Twice a Day (BID) + Rituximab 375 mg/m2 + Lenalidomide 20 mg Daily (QD)) | 21 |
| Total | 113 |
Baseline characteristics
| Characteristic | P1: RR Acalabrutinib 100 mg BID + Rituximab | P1: RR Acalabrutinib 200 mg QD | P1: TN Acalabrutinib 100 mg BID + Rituximab | P2: Acalabrutinib | P2: Acalabrutinib + Rituximab | P3: Acalabrutinib + Rituximab + Lenalidomide 15 mg | P3: Acalabrutinib + Rituximab + Lenalidomide 20 mg | Total | P1: RR Acalabrutinib 100 mg BID |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.7 Years STANDARD_DEVIATION 10.6 | 59.0 Years STANDARD_DEVIATION 21.2 | 59.6 Years STANDARD_DEVIATION 12.2 | 66.0 Years STANDARD_DEVIATION 10 | 43.0 Years | 62.5 Years STANDARD_DEVIATION 9.7 | 63.0 Years STANDARD_DEVIATION 9.7 | 64.0 Years STANDARD_DEVIATION 11.2 | 63.3 Years STANDARD_DEVIATION 16 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 7 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 3 Participants | 10 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 11 Participants | 2 Participants | 12 Participants | 41 Participants | 1 Participants | 5 Participants | 17 Participants | 101 Participants | 12 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 13 Participants | 2 Participants | 12 Participants | 38 Participants | 1 Participants | 7 Participants | 17 Participants | 101 Participants | 11 Participants |
| Region of Enrollment Canada | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 5 Participants | 9 Participants | 0 Participants |
| Region of Enrollment Italy | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants |
| Region of Enrollment United States | 13 Participants | 2 Participants | 13 Participants | 36 Participants | 1 Participants | 8 Participants | 16 Participants | 101 Participants | 12 Participants |
| Sex: Female, Male Female | 8 Participants | 1 Participants | 8 Participants | 17 Participants | 1 Participants | 1 Participants | 6 Participants | 48 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 5 Participants | 26 Participants | 0 Participants | 7 Participants | 15 Participants | 65 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 1 / 13 | 0 / 2 | 0 / 13 | 7 / 43 | 0 / 1 | 1 / 8 | 3 / 21 |
| other Total, other adverse events | 12 / 12 | 13 / 13 | 2 / 2 | 13 / 13 | 41 / 43 | 1 / 1 | 8 / 8 | 21 / 21 |
| serious Total, serious adverse events | 2 / 12 | 5 / 13 | 0 / 2 | 3 / 13 | 9 / 43 | 1 / 1 | 4 / 8 | 11 / 21 |
Outcome results
Primary
Part 1: Incidence of Treatment-emergent Adverse Events.
Treatment-emergent adverse events were used to characterize the safety profile of acalabrutinib alone or in combination with rituximab in participants with relapsed/refractory follicular lymphoma (R/R FL).
Time frame: From the first dose of study drug until study discontinuation, 30 days after the last dose of study drug or one day before the first subsequent anticancer therapy, whichever was earlier, up to 80.7 months (the maximum participant's time on this study).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Acalabrutinib 100 mg BID | Part 1: Incidence of Treatment-emergent Adverse Events. | 12 Number of participants |
| Part 1: Acalabrutinib 100 mg BID + Rituximab | Part 1: Incidence of Treatment-emergent Adverse Events. | 13 Number of participants |
| Part 1: Relapsed or Refractory Acalabrutinib 200 mg QD | Part 1: Incidence of Treatment-emergent Adverse Events. | 2 Number of participants |
| Part 1: Acalabrutinib 100 mg Rituximab | Part 1: Incidence of Treatment-emergent Adverse Events. | 13 Number of participants |
Primary
Part 2: Investigator Assessed Objective Response Rate (ORR) According to the Lugano Classification for Non-Hodgkin Lymphoma (NHL).
The objective response rate (ORR) is used to characterize the activity of acalabrutinib alone or in combination with rituximab in participants with relapsed/refractory marginal zone lymphoma (R/R MZL).
Time frame: Based on all response assessments since the first dose of study drug until study discontinuation or the initiation of subsequent anticancer therapy, whichever was earlier, up to 65.1 months (the maximum participant's time on this study).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Acalabrutinib 100 mg BID | Part 2: Investigator Assessed Objective Response Rate (ORR) According to the Lugano Classification for Non-Hodgkin Lymphoma (NHL). | 60.5 Percentage of participants |
| Part 1: Acalabrutinib 100 mg BID + Rituximab | Part 2: Investigator Assessed Objective Response Rate (ORR) According to the Lugano Classification for Non-Hodgkin Lymphoma (NHL). | 0 Percentage of participants |
Primary
Part 3: Incidence of Treatment-emergent Adverse Events.
Treatment-emergent adverse events were used to characterize the safety of acalabrutinib in combination with rituximab and lenalidomide in participants with relapsed/refractory follicular lymphoma (R/R FL).
Time frame: From the first dose of study drug until study discontinuation, 30 days after the last dose of study drug or one day before the first subsequent anticancer therapy, whichever was earlier, up to 54.3 months (the maximum participant's time on this study).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Acalabrutinib 100 mg BID | Part 3: Incidence of Treatment-emergent Adverse Events. | 8 Number of participants |
| Part 1: Acalabrutinib 100 mg BID + Rituximab | Part 3: Incidence of Treatment-emergent Adverse Events. | 21 Number of participants |