An Open-label, Phase 1b/2 Study of Acalabrutinib Alone or in Combination Therapy in Subjects With B-cell Non-Hodgkin Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- acalabrutinib
- Conditions
- Non Hodgkin Lymphoma
- Sponsor
- Acerta Pharma BV
- Enrollment
- 113
- Locations
- 1
- Primary Endpoint
- Part 1: Incidence of Treatment-emergent Adverse Events.
- Status
- Active, not recruiting
- Last Updated
- 6 months ago
Overview
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
Investigators
Eligibility Criteria
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
- •Subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criterion #4;
- •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 ≤
- •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
Arms & Interventions
Part 1: acalabrutinib Regimen 1
acalabrutinib Regimen 1 for relapsed, refractory Follicular Lymphoma subjects
Intervention: acalabrutinib
Part 1: acalabrutinib Regimen 2
acalabrutinib Regimen 2 + rituximab for relapsed, refractory, or treatment naive Follicular Lymphoma subjects
Intervention: acalabrutinib
Part 1: acalabrutinib Regimen 2
acalabrutinib Regimen 2 + rituximab for relapsed, refractory, or treatment naive Follicular Lymphoma subjects
Intervention: rituximab (IV)
Part 2: acalabrutinib Regimen 1
acalabrutinib Regimen 1 for relapsed, refractory Marginal Zone Lymphoma subjects
Intervention: acalabrutinib
Part 2: acalabrutinib Regimen 2
acalabrutinib Regimen 2 + rituximab for relapsed, refractory Marginal Zone Lymphoma subjects
Intervention: acalabrutinib
Part 2: acalabrutinib Regimen 2
acalabrutinib Regimen 2 + rituximab for relapsed, refractory Marginal Zone Lymphoma subjects
Intervention: rituximab (IV)
Part 3: acalabrutinib Regimen 1
acalabrutinib Regimen + lenalidomide + rituximab for relapsed, refractory Follicular Lymphoma subjects
Intervention: acalabrutinib
Part 3: acalabrutinib Regimen 1
acalabrutinib Regimen + lenalidomide + rituximab for relapsed, refractory Follicular Lymphoma subjects
Intervention: rituximab (IV)
Part 3: acalabrutinib Regimen 1
acalabrutinib Regimen + lenalidomide + rituximab for relapsed, refractory Follicular Lymphoma subjects
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Part 1: Incidence of Treatment-emergent Adverse Events.
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).
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).
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).
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.
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).
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).