Splenic Marginal Zone Lymphoma MedDRA version: 14.1 Level: PT Classification code 10062113 Term: Splenic marginal zone lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentr
Sponsors
INTERNATIONAL EXTRANODAL LYMPHOMA STUDY GROUP (IELSG)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria •Initial diagnosis of CD20+ Splenic Marginal Zone Lymphoma morphology confirmed by histology, cytology, immunophenotype (chromosomal abnormalities by quantitative multiplex PCR of short fluorescent fragments (QMPSF) is optional) according to WHO 2008 classification of Lymphoma criteria or according to the recommendation of the Splenic Lymphoma Group (Matutes et al. Leukemia 2008) for non splenectomized patient. 1.If patients not splenectomised: diagnosis on bone marrow biopsy (histology and immunohystochemistry), and blood (cytology, immunophenotype), chromosomal abnormalities by QMPSF optional. 2.If patients splenectomised diagnosis on spleen, bone marrow biopsy (histology and immunohistochemistry), and blood (cytology, immunophenotype) chromosomal abnormalities by QMPSF optional. •No previous treatment with immunotherapy or chemotherapy or radiotherapy unless pretreatment by monocorticotherapy. •Patients requiring a treatment with at least one of the following situation: 1)Symptomatic SMZL in not splenectomized patients a)Bulky (arbitrarily defined as =6 cm below left costal margin) or progressive or painful splenomegaly, without enlarged lymphoadenopathy, with or without cytopenia, not eligible for splenectomy or not willing splenectomy b)One of the following symptomatic/progressive cytopenias: Hb 6 months. •Voluntary signed informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. •The following laboratory values at screening: 1.Absolute neutrophil count (ANC) ?1.000/mm3 and Platelets ?100.000/mm3, unless these abnormalities are related to bone marrow infiltration or to hypersplenism. 2.Aspartate transaminase (AST) ?2 x ULN; Alanine transaminase (ALT) ?2 x ULN; total bilirubin ?1.5 x ULN. 3.Creatinine clearance = 10 ml/min (as calculated by the Cockcroft-Gault formula - Appendix I). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: Exclusion criteria •Any type of lymphoma other than SMZL. •Patients with proven biopsy of histological transformation. •Contraindication to any drug contained in the chemotherapy regimen. •Myocardial infarction during last 3 months or unstable coronary disease or uncontrolled chronic symptomatic congestive heart insufficiency NYHA III – IV (Appendix H). •Uncontrolled hypertension. •Uncontrolled diabetes mellitus as defined by the investigator. •Active systemic infection requiring treatment. •HIV positive serology. •Active hepatitis B virus infection (presence of antigen HBS+; in case of presence of antibody anti HBC+ and anti HBS+, controls should be organized according to guidelines of AASLD and l’EASL). •Active and previously untreated HCV infection •Prior history of malignancies other than lymphoma within 3 years (except for complete resection of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy). Patients previously diagnosed with prostate cancer are eligible if (1) their disease was T1-T2a, N0, M0, with a Gleason score ?7, and a prostate specific antigen (PSA) ?10 ng/mL prior to initial therapy, (2) they had definitive curative therapy (ie, prostatectomy or radiotherapy) ?2 years before Day 1 of Cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or 1 months) of systemic corticosteroids. •Serious medical or psychiatric illness likely to interfere with participation in this clinical study. •Prior participation in another study with experimental drug during the last 4 months. •Pregnant or currently breast-feeding woman.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy of R-Bendamustine measured by Complete Response rate.;Secondary Objective: Efficacy measured by •Overall Response Rate (ORR) •Safety and tolerability measured by toxicities of R-Bendamustine evaluated by assessment of laboratory parameters and adverse events coded with NCI Common Toxicity Criteria, version 4.0 (Appendix F) •3-year Progression Free Survival (PFS) •Duration Of Response (DOR) •3-year Event Free Survival (EFS) •Time to Next Treatment (TTNT) •3-year Overall Survival (OS) •Risk of histological transformation •5 year-PFS and - OS;Primary end point(s): Efficacy of R-Bendamustine measured by Complete Response rate. Complete response rate will be assessed by means of CT-scan, Immunophenotype in blood and bone marrow (PET-scan optional). Response criteria will be determined as follows: Complete response (CR) requires the disappearance of all evidence of disease a.Regression to normal size on CT of organomegaly (splenomegaly, hepatomegaly and lymphoadenopathies) b.Normalization of the blood counts (Hb >12 g/dl; platelets >100.000/mm3; neutrophils >1.500/mm3 and no evidence of circulating clonal B-cells) c.No evidence or minor (50%, of measurable signs of the disease from nadir- Relapsed disease: Reappearance of any measurable sign of the disease. A patient is defined as a responder if she/he has a complete or partial response. Patients without response assessment (due to whatever reason) will be considered as non-responders.;Timepoint(s) of evaluation of this end point: 24 weeks from beginning of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ?Overall Response Rate (ORR) (Complete response + Partial response) ?Safety and tolerability measured by toxicities of R-Bendamustine evaluated by assessment of laboratory parameters and adverse events coded with NCI Common Toxicity Criteria, version 4.0 (Appendix J). ?3-year Progression Free Survival (PFS), defined as the time from entry into the study until reappearance of cytopenia or lymphoma relapse/ progression with enlarged lymph node(s) or spleen if present, histologic transformation or death as a result of any cause. Responding patients, patients who are lost to follow up, who withdrawal the consent or drop-out due to adverse event will be censored at their last assessment date. Patients died due to tumor will be considered in progression. Patients died for any other cause will be censored to the death date. ?Duration of Response (DR), is defined for all patients who achieved a response (CR and PR) and is measured from the time of response until the date of first documentation of progression or relapse. Patients without relapse or progression will be censored at their last assessment date. Patients died due to tumor will be considered in progression. Patients died for any other cause will be censored to the death date. ?3-year Event Free Survival (EFS), will be measured from the day of treatment start to the date of documentation of one of the following events: any treatment failure including disease progression, or discontinuation of treatment for any reason (eg, disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death). Responding patients, patients who are lost to follow up, who withdrawal the consent or drop-out due to adverse event will be censored at their last assessment date. ?Time To Next Treatment (TTNT), defined as the time from the end of the chemo-immunotherapy course to the day of next treatment commencement irrespective of cause ?3-year Overall Surviv | — |
Countries
Italy
Contacts
Public ContactSegreteria Amministrativa
Fondazione Italiana Linfomi ONLUS
Outcome results
None listed