Study of acalabrutinib and tafasitamab in patients with marginal zone lymphoma

Phase 1

• Conditions: Marginal Zone Lymphomas refractory to or in first or greater relapse after prior systemic therapy; MedDRA version: 20.0Level: PTClassification code 10076596Term: Marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-004396-38-IT
• Lead Sponsor: IELSG - INTERNATIONAL EXTRANODAL LYMPHOMA STUDY GROUP

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-04
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

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:
· MZL: 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.
- 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 (Appendix A).
- 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 lever and renal function.
- Adequate coagulation parameters
- Women with childbearing potential who are using effective contraception 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

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 a
- 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 diseases.
- 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).
- 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.
- Malabsorption syndrome or other condition that precludes enteral route of administration.
- Any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment.
- 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;
- 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 (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to antacids are eligible for enrollment to this study.
- Concurrent participation in another therapeutic clinical trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the efficacy of tafasitamab in combination with acalabrutinib in patients with relapsed or refractory MZL patients;Secondary Objective: To evaluate the safety profile of tafasitamab in combination with acalabrutinib in patients with relapsed or refractory MZL.<br><br>To further evaluate the efficacy of tafasitamab in combination with acalabrutinib in patients with relapsed or refractory MZL.;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: Between 11- 13 weeks after treatment start, at the end of cycles 6, 12,18, 24 (each cycle is 28 days)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Progression free survival; Duration of response; Overall Survival; Adverse events (AE) type and severity according to CTCAE v5.0 and relationship to study treatment; Overall Response Rate;Timepoint(s) of evaluation of this end point: From the first IMP dose to date of disease progression or date of death for any reason or censored at the date of the last follow-up visit, whichever occurs earlier; From the date of first documented response to the date of progression or the date of death for any cause until 3 years from last treatment dose; From the first IMP dose to the date of death for any reason or censored at the date of the last contact, whichever occurs earlier; From the time of informed consent signature until 28 days after treatment discontinuation or until resolution of all treatment related AEs, whichever occurs later;; Between 11- 13 weeks after treatment start, at the end of cycles 6, 12, 18, 24 (each cycle is 28 days)