RITUXIMAB for Mantle cell lymphoma

Inclusion criteria

• {"criterion_text":"- Subjects with confirmed diagnosis of Mantle Cell Lymphoma (World Health Organization Classification, WHO 2008). Classical, small-cell variants and marginal-zone variants can be included."}
• {"criterion_text":"- Stable disease without evidence of clinical progression criteria for at least 3 months. Patients in prolonged therapeutic abstention may be included."}
• {"criterion_text":"- Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug."}
• {"criterion_text":"- Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [ß-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study."}
• {"criterion_text":"- Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study."}
• {"criterion_text":"- Age 18 years or older."}
• {"criterion_text":"- Subjects must not have received any prior therapies (excluding diagnostic splenectomy)."}
• {"criterion_text":"- Asymptomatic patients."}
• {"criterion_text":"- Ann Arbor clinical stages I-IV."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status <2 (0-1)."}
• {"criterion_text":"- Subjects with a non-nodal MCL presentation with mainly bone marrow or peripheral blood involvement."}
• {"criterion_text":"- Other asymptomatic clinical presentations are acceptable in case of low tumor burden, including nodal MCL with lymph node enlargement ≤ 3 cm in the maximum diameter and with low proliferation index (Ki-67 ≤ 30%)."}
• {"criterion_text":"- The following laboratory values at screening: ● ● Neutrophil count ≥ 1×10e9/L, Hemoglobin level ≥ 100 g/L or platelet count ≥ 100×10e9/L Transaminases (AST and ALT) ≤ 3 x ULN ●Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin ●Creatinine ≤ 2 x ULN or calculated creatinine clearance ≥ 40 mL/min/1.73m2"}

Exclusion criteria

• {"criterion_text":"- Aggressive histological variants: blastic and pleomorphic variants (blastoid)."}
• {"criterion_text":"- Known CNS infiltration."}
• {"criterion_text":"- Subjects with expected therapy requirement for MCL in a short time (< 3 months)."}
• {"criterion_text":"- Patients with active hepatitis B or C infection or HIV infection. Positive test results for chronic HBV infection (defined as positive HBsAg serology) or positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing) will be excluded with the following exceptions. 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 or antiviral prophylaxis. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination or prior but cured hepatitis B are eligible. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA."}
• {"criterion_text":"- Anticoagulation requirement with vitamin K antagonists."}
• {"criterion_text":"- Past medical history of stroke or intracranial haemorrhage within 6 months prior to inclusion"}
• {"criterion_text":"- Required medication with strong CYP3A4/5 inhibitors."}
• {"criterion_text":"- Any serious comorbidity that makes the patient unacceptable for receiving the treatment"}
• {"criterion_text":"- Concomitant or previous malignancies the last 2 years other than basal skin cancer or in situ uterine cervix cancer."}
• {"criterion_text":"- Pregnancy or lactation."}
• {"criterion_text":"- Major surgery within 4 weeks of inclusion."}
• {"criterion_text":"- Proliferation index measured by Ki-67 > 30%."}
• {"criterion_text":"- Clinically significant cardiovascular disease 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."}
• {"criterion_text":"- Vaccinated with live, attenuated vaccines within 4 weeks of randomization."}
• {"criterion_text":"- Uncontrolled systemic infection requiring intravenous (IV) antibiotics."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- B-cell monoclonal lymphocytosis with MCL phenotype."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status ≥2."}
• {"criterion_text":"- Presence of B symptoms or any relevant symptoms related to the MCL."}
• {"criterion_text":"- Nodal clinical forms with lymph node enlargement > 3 cm (maximum diameter)."}
• {"criterion_text":"- Cytopenias attributable to MCL: Neutrophil count < 1×10e9/L, Hemoglobin level < 100 g/L or platelet count < 100×10e9/L."}
• {"criterion_text":"- Organ dysfunction related to MCL including creatinine level > 2 ULN or altered liver biochemistry (> 3x ULN)."}
• {"criterion_text":"- Gradual increase in different determinations of serum LDH attributable to MCL that exceeds 20% of the ULN."}

Primary endpoints

• {"endpoint_text":"- Rate of complete remission (CR) achieved at 12 months of I+R combination.","definition_or_measurement_approach":"Rate of complete remission (CR) measured at 12 months of treatment with the Ibrutinib plus Rituximab combination (assessment at 12 months)."}

Secondary endpoints

• {"endpoint_text":"- To determine the overall response rate (ORR) at 12 months, Progression free survival (PFS), duration of response (DOR) and overall survival (OS).","definition_or_measurement_approach":"ORR at 12 months; PFS, DOR and OS as time-to-event endpoints (no further measurement detail provided)."}
• {"endpoint_text":"- To determine the rate of negative minimal residual disease (MRD), the time to obtain a molecular response and the median duration of the molecular response in I+R responding patients.","definition_or_measurement_approach":"MRD negativity rate, time to molecular response and median duration of molecular response in responding patients (molecular assays specified in protocol but not detailed in CTIS summary)."}
• {"endpoint_text":"- Rates of AEs, SAEs, and SUSARs by CTC grade (Version 4.03) during I+R treatment","definition_or_measurement_approach":"Adverse events, serious adverse events and SUSARs classified by CTC v4.03."}
• {"endpoint_text":"- To assess the health-related quality of life (QOL) during treatment.","definition_or_measurement_approach":"Health-related quality of life measured during treatment (specific instruments not detailed in CTIS summary)."}
• {"endpoint_text":"- Genomic studies in indolent clinical forms of MCL (IGHV mutational status, DNA copy-number and whole exome sequencing)","definition_or_measurement_approach":"Genomic analyses including IGHV mutational status, DNA copy-number assessment and whole exome sequencing."}

Spain

Earliest CTIS Part Ii Submission Date

11-06-2024

Latest Decision Or Authorization Date

12-12-2025

Processing Time Days

549

Number Of Sites

12

Number Of Participants

50

Primary sponsor

Full Name

Fundacion Geltamo

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain