Study of Acalabrutinib and Tafasitamab in MZL Patients

• Status: Recruiting
• Trial end date: 2028-03-15
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter open label phase II trial in patients with previously treated Marginal Zone Lymphomas.

The aim of the study is to evaluate the efficacy and the safety of tafasitamab in combination with acalabrutinib.

Twenty-four patients are expected to be enrolled and treated every 28 days with acalabrutinib and tafasitamab for 24 cycles.

The study consists of two parts, which are performed sequentially. The first part is a safety run-in to evaluate the safety data once 6 patients (representing the 25% of the total cohort) have completed the first cycle of treatment. An Independent Data Monitoring Committee (IDMC) will provide an independent assessment of this evaluation.

The second part starts after the outcome of this evaluation and will include the remaining 18 patients. The 6 patients of the safety run-in phase will be considered for the final evaluation of the study.

Between 11 - 13 weeks, patients showing partial or complete response (PR, CR) will continue treatment, while patients showing stable disease (SD) will discontinue it. However, patients in SD who benefit from therapy may continue to be treated, after agreement between the Investigator and the Sponsor.

Patients who complete the 24 cycles of treatment will enter the follow-up phase up to 3 years from patient's last study treatment dose (about 5 years from treatment start).

Patients who discontinue treatment before cycle 24 for any reason will be followed for up to 3 years (every 6 months for the first year and yearly for the second and third year) from the patient's last study treatment dose.

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• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: International Extranodal Lymphoma Study Group (IELSG)
• Treatments: Acalabrutinib

Criteria

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.

• 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:

• Patients with a prior malignancy and treated with curative intention, unless all treatments of that malignancy were completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low-risk of recurrence and/or no late recurrence.

• 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