ACALABRUTINIB for Marginal zone lymphoma | Relapsed or refractory marginal zone lymphoma

Inclusion criteria

• {"criterion_text":"- Ability to understand and willingness to sign a written informed consent\n- Adequate kidney and liver function\n- Adequate coagulation parameters\n- Women with childbearing potential who are using highly effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and for at least 3 months after the last IMP dose\n- Men who agree not to father a child during trial treatment and for at least 3 months after the last IMP dose\n- Patient able and willing to swallow trial drugs as whole capsule\n- Histologically confirmed diagnosis of MZL\n- Disease refractory to or in first or greater relapse after prior systemic therapy\n- In need of treatment disease satisfying the following criteria: • EMZL: symptomatic lymphoma or with other treatment indications (overt progression, deep invasion, bulky disease, impending organ damage, patient preference), symptomatic disseminated disease, contraindications to radiotherapy (RT), failure after antibiotics or after local therapy, • SMZL: presence of progressive or symptomatic splenomegaly and/ or any progressive cytopaenias, • NMZL: B symptoms, deterioration of peripheral blood counts due to lymphoma infiltration of the bone marrow, rapid enlargement of lymph nodes or compression of vital organs by bulky disease\n- Measurable or non-measurable lesions where the response is nevertheless evaluable by non-imaging means (e.g., gastric or bone marrow infiltrations)\n- Ann Arbor Stage I-IV (Appendix A)\n- ECOG performance status of 0, 1 or 2 with no deterioration over the previous 2 weeks prior to registration\n- Age ≥ 18 years\n- Absolute neutrophil count (ANC) ≥ 1.000/mm3 and platelets ≥ 100.000/mm3, unless these abnormalities are related to bone marrow infiltration or to hypersplenism"}

Exclusion criteria

• {"criterion_text":"- History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following: a. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study, b. Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for ≥3 years without further treatment\n- Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML)\n- Concomitant diseases that require anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists and patients treated with dual anti-platelet therapy\n- Malabsorption syndrome or other condition that precludes enteral route of administration\n- Known hypersensitivity to trial drugs or to any component of the trial drugs\n- Concomitant treatment with strong CYP3A inducers or inhibitors\n- Treatment with proton pump inhibitors. Subjects receiving proton pump inhibitors who switch to antacids are eligible for enrollment to this study\n- Concurrent participation in another therapeutic clinical trial\n- History of or ongoing confirmed central nervous system (CNS) lymphoma\n- Patients who received any IMP within 30 days or 5 half-lives (whichever is shorter) before the first dose of the study IMP\n- Patients who received a live virus vaccination within 28 days of the first IMP dose\n- Any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment\n- Pregnant or breastfeeding women\n- Active human immunodeficiency virus (HIV) or active chronic hepatitis C or hepatitis B virus infection. Patients positive for hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA\n- Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with > 20 mg daily of prednisone dose or equivalent\n- Major surgery and any systemic anti-cancer treatment within 3 weeks prior to registration. If patients had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first IMP dose\n- Prior exposure to a BTK inhibitor or CD19-targeted therapy\n- Steroid therapy for anti-neoplastic intent\n- Severe or uncontrolled cardiovascular diseases\n- History of cerebrovascular accident or intracranial hemorrhage within 6 months prior to registration and known bleeding disorders (e.g., von Willebrand's disease or hemophilia)"}

Primary endpoints

• {"endpoint_text":"- Complete response rate (CR) as best response to treatment, defined according to the international Revised Response Criteria for Malignant Lymphoma . For patients with SMZL, response is defined according to Matutes et al. 2008 and for patients with gastric lymphomas, histological response is evaluated according to GELA scoring system","definition_or_measurement_approach":"Defined according to the international Revised Response Criteria for Malignant Lymphoma. For SMZL use Matutes et al. 2008 definitions; for gastric lymphomas histological response per GELA scoring system."}

Secondary endpoints

• {"endpoint_text":"- Adverse events type and severity according to CTCAE v5.0 and relationship to study treatment","definition_or_measurement_approach":"Adverse events graded and classified according to CTCAE v5.0; relationship to study treatment assessed per protocol."}
• {"endpoint_text":"- Overall response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}

Austria

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

22-07-2024

Processing Time Days

38

Number Of Sites

1

Number Of Participants

6

Italy

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

22-07-2024

Processing Time Days

38

Number Of Sites

7

Number Of Participants

16

Primary sponsor

Full Name

Association International Extranodal Lymphoma Study Group (IELSG)

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Switzerland

Third parties

• {"country":"","full_name":"Astra Zeneca AG","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Incyte Bioseciences International Sarl","duties_or_roles":"Monetary support","organisation_type":""}