Study of Acalabrutinib and Tafasitamab in MZL Patients

Inclusion Criteria: * Ability to understand and willingness to sign a written informed consent * Histologically confirmed diagnosis of MZL. * Disease refractory to or in first or greater relapse after prior systemic therapy. * 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 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. * Measurable or non-measurable lesions where the response is nevertheless evaluable by non-imaging means (e.g., gastric or bone marrow infiltrations). * Ann Arbor Stage I-IV. * ECOG performance status of 0, 1 or 2 with no deterioration over the previous 2 weeks prior to registration . * Age ≥ 18 years. * Absolute neutrophil count (ANC) ≥ 1.000/mm3 and platelets ≥ 100.000/mm3, unless these abnormalities are related to bone marrow infiltration or to hypersplenism. * Adequate hepatic function, renal function and coagulation parameters * 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. * Men who agree not to father a child during trial treatment and for at least 3 months after the last IMP dose. * Patient able and willing to swallow trial drugs as whole capsule Exclusion Criteria: * History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following: 1. 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, 2. 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. * Major surgery and any systemic anti-cancer treatment within 3 weeks prior to registration. * Prior exposure to a BTK inhibitor or CD19-targeted therapy. * Steroid therapy for anti-neoplastic intent. * Severe or uncontrolled cardiovascular disease * History of cerebrovascular accident or intracranial hemorrhage within 6 months prior to registration and known bleeding disorders * Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML). * Concomitant diseases that require anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists and patients treated with dual anti-platelet therapy. Patients being treated with factor Xa inhibitors (e.g. rivaroxaban, apixaban, edoxaban), direct thrombin inhibitors (e.g. dabigatran) LMWH, or single anti-platelets agents (e.g. aspirin, clopidogrel) can be included, but must be properly informed about the potential risk of bleeding. * Malabsorption syndrome or other condition that precludes enteral route of administration. * Active human immunodeficiency virus (HIV) or active chronic hepatitis C or hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment. * Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune. thrombocytopenia) requiring steroid therapy with \> 20 mg daily of prednisone dose or equivalent. * Known hypersensitivity to trial drugs or to any component of the trial drugs. * Concomitant treatment with strong CYP3A inducers or inhibitors * Treatment with proton pump inhibitors. Subjects receiving proton pump inhibitors who switch to antacids are eligible for enrollment to this study. * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with trial participation or IMPs administration or may interfere with the interpretation of trial results and/or would make the patient inappropriate for enrolment into this trial. * Concurrent participation in another therapeutic clinical trial * History of or ongoing confirmed central nervous system (CNS) lymphoma * Patients who received any IMP within 30 days or 5 half-lives (whichever is shorter) before the first dose of the study IMP * Pregnant or breastfeeding women * Patients who received a live virus vaccination within 28 days of the first IMP dose