RITUXIMAB for Marginal zone lymphoma|Extranodal marginal zone lymphoma (MALT lymphoma)|Splenic marginal zone lymphoma|Nodal marginal zone lymphoma

Inclusion criteria

• {"criterion_text":"- To be eligible for inclusion, each patient must fulfill all of the following criteria: Chemotherapy and immunotherapy-naïve, symptomatic and in need of treatment patients, with histologically proven CD20-positive MZL, not eligible for local therapy, including: 1. EMZL (MALT Lymphoma) patients with MALT- IPI score 1-3 in need of systemic therapy. Either de novo or relapsed following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma) arisen at any extranodal site with MALT-international prognostic index (IPI) score 1-2 at the time of study entry. 1.1. The following patients with gastric MALT Lymphoma can be entered: a) H. pylori-negative cases, either de novo (non pretreated) or at relapse following local therapy (i.e., surgery, radiotherapy or antibiotics). b) H. pylori-positive cases at diagnosis, who either first line antibiotics or further local treatment (surgery or radiotherapy), including patients with: - clinical (endoscopic) and histological evidence of disease progression at any time post H. pylori eradication; - clinical (endoscopic) and histological relapse (without H. pylori re-infection), after a remission patients; - persistent (stable) lymphoma at = 1 year post H. pylori eradication. 1.2. Similar consideration may be applied to patients with ocular adnexal lymphoma treated with antibiotics.\n- Adequate kidney function\n- For women of childbearing potential only: negative serum pregnancy test done within 7 days prior to study drugs administration or within 14 days if with a confirmatory urine pregnancy test within 7 days prior to the first study drugs administration.\n- Fertile male or female patients of childbearing potential and their partners must use higly effective contraception during the study and for at least 12 months after the last dose of subcutaneous rituximab and 3 months after the last dose of ibrutinib.In case hormonal methods of birth control is used a barrier method must be added.\n- Ability to understand and the willingness to sign a written informed consent document\n- SMZL patients in need of therapy. Either de novo or relapsed following local therapy [including surgery and antiviral therapy for Hepatitis C virus (HCV)]. Patient must have a symptomatic disease requiring treatment and be not eligible for splenectomy or not willing to undergo splenectomy. 2.1. Patients with SMZL can be entered if any of the following criteria is present: a) bulky progressive or painful splenomegaly; b) enlarged lymph nodes or involvement of extranodal sites with or without cytopenias, i.e. involvement of =3 nodal sites, each with a diameter of =3 cm. Any nodal tumor mass with a diameter of =7 cm (GELG criteria, as adopted in follicular lymphoma) ; c) one of the following symptomatic/progressive cytopenias: - Hgb < 10 g/dL; - ANC < 1000/µL: - PLT< 80 000/µL whatever the reason (autoimmune or hypersplenism or bone marrow infiltration). 2.2. Splenectomised patients with rapidly raising lymphocyte counts, lymphadenopathy or involvement of extranodal sites can be entered. 2.3. SMZL with concomitant HCV infection who have not responded to or are relapsed after antiviral therapy can be entered\n- NMZL patients in need of therapy Either, de novo presenting with disseminated disease or relapsed after local radiotherapy or following antiviral therapy for HCV. Localized nodal MZL is not eligible.\n- Measurable or evaluable disease\n- Ann Arbor II-IV (see Appendix B). Stage I disease may be eligible only if not candidate to local therapy (surgery or radiotherapy).\n- Age >/= 18\n- Life expectancy of at least 1 year\n- ECOG Performance status 0-2\n- Adequate bone marrow function"}

Exclusion criteria

• {"criterion_text":"- Any type of lymphoma other than MZL (including MZL with histologic transformation to high-grade lymphoma)\n- Active, severe infections\n- Pregnancy or breastfeeding\n- Any 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 ibrutinib capsules, or put the study outcomes at undue risk.\n- Clinically significant cardiovascular diseases such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification\n- Any serious medical or psychiatric illness likely to interfere with participation in this clinical study\n- Prior history of malignancies other than MZL within 3 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer\n- Current enrolment or participation in another therapeutic clinical trial within 28 days prior to treatment start\n- Clinically significant hypersensitivity (e.g., anaphylactic or anaphylactoid reactions to the compound of ibrutinib and/or rituximab themselves or to the excipients in their formulation).\n- Active HCV or Hepatitis B virus (HBV) infections. Positive test results for chronic HBV infection (defined as positive HBsAg serology).\n- Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing and taking specific antiviral prophylaxis, according to local policy. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination are eligible\n- Any previous systemic treatment with immunotherapy or chemotherapy or with BTK inhibitors.\n- Localized (stage IE and IIE) gastric, ocular and cutaneous MALT lymphoma that may benefit from local therapy only (surgery or radiotherapy).\n- Known CNS involvement of MZL.\n- Major surgery within 4 weeks prior to registration\n- History of stroke or intracranial bleeding within 6 months\n- Known bleeding diathesis (eg, von Willebrand’s disease) or hemophilia.\n- Concurrent use of warfarin of other vitamin K antagonists\n- Concurrent use of strong cytochrome P450 (CYP)3A4/5 inhibitors\n- Positive test results for hepatitis C. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA\n- HIV infection or immunodeficiency"}

Primary endpoints

• {"endpoint_text":"- a) Complete Response (CR) rate at 12 months\n- b) PFS at 5 years assessed by the investigators, according to revised response criteria for malignant lymphomas, from study entry to death from any cause or PD","definition_or_measurement_approach":"CR rate at 12 months: proportion of patients achieving Complete Response at 12 months per investigator assessment. PFS at 5 years: progression-free survival assessed by investigators according to revised response criteria for malignant lymphomas, measured from study entry to death from any cause or disease progression (PD)."}

Secondary endpoints

• {"endpoint_text":"- Acute and long-term safety evaluated by assessment of laboratory parameters and adverse events coded with NCI Common Toxicity Criteria, version 4.0","definition_or_measurement_approach":"Safety assessed by laboratory parameters and adverse event reporting coded using NCI CTCAE (version indicated)."}
• {"endpoint_text":"- Complete Response rate at 24 months","definition_or_measurement_approach":"Proportion of patients achieving CR at 24 months per investigator assessment."}
• {"endpoint_text":"- Overal Response Rate (ORR) at 12 and 24 months","definition_or_measurement_approach":"Overall response rate (ORR) at specified timepoints per investigator assessment according to lymphoma response criteria."}
• {"endpoint_text":"- Overall Survival","definition_or_measurement_approach":"Overall survival measured from study entry to death from any cause."}

Belgium

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

24-02-2026

Processing Time Days

655

Number Of Sites

1

Number Of Participants

12

Portugal

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

03-06-2024

Processing Time Days

390

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

24-02-2026

Processing Time Days

655

Number Of Sites

16

Number Of Participants

110

France

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

26-02-2026

Processing Time Days

657

Number Of Sites

12

Number Of Participants

54

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":"France","full_name":"LYSARC","duties_or_roles":"Sponsor duties codes listed: 1,12,15 (value: centralized anatomopathologocal review (LYSA-P) and for SMZL patients a cytological review at LYON), 2,8","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Centre Hospitalier Universitaire De Dijon","duties_or_roles":"Code 15 (Biomarker analysis)","organisation_type":"Hospital/Clinic/Other health care facility"}