ACALABRUTINIB for Relapsed/Refractory marginal zone lymphoma | B-cell non-Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Men and women ≥18 years of age.\n- Histologically confirmed MZL including splenic, nodal, and extranodal sub-types\n- Previous therapy: a. Cohort 1: Previously received 1 or more lines of systemic therapy including at least 1 CD20-directed regimen (either as monotherapy or as chemoimmunotherapy for MZL) with documented failure to achieve at least PR, or documented disease progression after the most recent treatment regimen. b.\tCohort 2: Previously received 1 or more lines of therapy including at least 1 prior systemic therapy for MZL or radiation therapy with documented failure to achieve at least PR, or document disease progression after the most recent treatment regimen.\n- Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 lesion that measures ≥2.0 cm in the longest dimension and ≥1.0 cm in the longest perpendicular dimension as assessed by CT scan).\n- ECOG performance status of ≤2.\n- Ability to understand the purpose and risks of the study and provide signed and dated informed consent"}

Exclusion criteria

• {"criterion_text":"- Prior malignancy (other than indolent B-cell NHL), 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.\n- Known history of infection with HIV.\n- Serologic status reflecting active hepatitis B or C infection.\n- History of allogeneic stem cell (or organ) transplantation.\n- History of stroke or intracranial hemorrhage within 6 months before the first dose of acalabrutinib.\n- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonist (e.g., phenprocoumon) within 7 days of first dose of study drug.\n- ANC <1.0 × 109/L or platelet count <100 × 109/L. For subjects with documented disease involvement in the bone marrow, ANC <0.50 × 109/L or platelet count <30 × 109/L.\n- Creatinine >1.5 × institutional ULN; total bilirubin >1.5 × ULN; and AST or ALT >2.5 × ULN.\n- Breastfeeding or pregnant.\n- Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.\n- History of or ongoing progressive multifocal leukoencephalopathy (PML).\n- Known medically apparent CNS lymphoma or leptomeningeal disease.\n- Known evidence of transformation to another aggressive lymphoma.\n- 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.\n- Known history of a bleeding diathesis (e.g., hemophilia, von Willebrand disease).\n- 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 using Fridericia formula (QTcF) >480 msec.\n- Prior exposure to a BCR inhibitor (e.g., BTK, or SYK inhibitors).\n- Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment or other conditions within 1 week before the first dose of study drug.\n- Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks before first dose of study drug."}

Primary endpoints

• {"endpoint_text":"- Efficacy: Investigator-assessed ORR according to the Lugano classification for NHL.","definition_or_measurement_approach":"Overall response rate (ORR) assessed by the investigator according to the Lugano classification for non-Hodgkin lymphoma."}

Secondary endpoints

• {"endpoint_text":"- Monitoring and recording AEs and SAEs; hematology, serum chemistry, serum Ig, and T/B/NK-cell count results; vital signs measurements; ECOG; and concomitant medications.","definition_or_measurement_approach":"Safety monitoring via adverse event (AE/SAE) reporting, laboratory tests (hematology, chemistry, serum Ig, lymphocyte subsets), vital signs, ECOG performance status, and concomitant medications recording."}
• {"endpoint_text":"- Investigator-assessed DOR, PFS, and OS according to the Lugano classification for NHL","definition_or_measurement_approach":"Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) assessed by investigator per the Lugano classification for NHL."}

Italy

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

28-05-2025

Processing Time Days

239

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

Acerta Pharma B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands

Contract research organisations

Name

IQVIA Limited

Responsibilities

sponsorDuties codes: 1, 12 (roles as recorded in CTIS; specific role text not provided)

Third parties

• {"country":"United States","full_name":"Astrazeneca Pharmaceuticals LP","duties_or_roles":"sponsorDuties codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1, 12","organisation_type":"Pharmaceutical company"}