Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma

NCT02853370 | Completed Phase 2 Results

• 1 other identifier: IELSG 36
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 30

Brief Summary

Splenic Marginal Zone Lymphoma (SMZL) is a well-defined low-grade B-cell lymphoma,considered as a rare neoplasm accounting for about 2% of all non-Hodgkin's lymphomas (NHL) and represents for most cases of otherwise unclassifiable chronic lymphoid B-cell cluster of differentiation antigen 5 (CD5)-lymphoproliferative disorders. SMZL is characterized by an almost exclusive involvement of the spleen and bone marrow and in about 25% of cases the disease pursues an aggressive course and most patients die of lymphoma progression within 3-4 years. Retrospective studies have indicated that purine analogous achieved very high response rates in both naïve and pre-treated patients. Moreover, the introduction of the anti-cluster of differentiation antigen 20 (CD20) humanized antibody rituximab, either used alone or in combination with chemotherapy has been reported to be very effective in producing a rapid clearance of neoplastic cells.

Conditions

Marginal Zone B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  Percentage of patients with complete response. Complete response to be assessed by means of CT-scan, Immunophenotype in blood and bone marrow (PET-scan optional) Complete response (CR) requires the disappearance of all evidence of disease 1. Regression to normal size on CT of organomegaly (splenomegaly, hepatomegaly and lymphoadenopathies) 2. 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) 3. No evidence or minor (\<5%) BM infiltration detected by immunohistochemistry

  At the end of treatment (After 24 weeks of treatment)

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  At the end of treatment (After 24 weeks of treatment)

• 3-year Progression Free Survival (PFS)

  3 years after study entry

• 3-years Duration of Response (DOR)

  3 years from study entry

• 3-years Event Free Survival (EFS)

  3 years after study entry

• 3-years Overall Survival Rate

  3 years after treatment start

Study Arms (1)

Bendamustine and Rituximab

EXPERIMENTAL

Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2\* Rituximab 375 mg/m2 i.v. d1\*\* Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2\* Rituximab 375 mg/m2 i.v. d1 From Cycle 4 to Cycle 6, every 4 weeks, depending on the response after the first 3 Cycles \*Or days 2-3 according to institutional/patient/physician preference \*\*Administration of Rituximab during cycle 1 and cycle 2 can be postponed to day 8 or 14 in case of risk of tumor lysis syndrome (TLS)

Drug: Bendamustine and Rituximab

Interventions

Bendamustine and Rituximab DRUG

Bendamustine and Rituximab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Initial diagnosis of CD20+ Splenic Marginal Zone Lymphoma morphology confirmed by histology, cytology, immunophenotype (chromosomal abnormalities by quantitative multiplex Polymerase Chain Reaction (PCR) of short fluorescent fragments (QMPSF) is optional) according to World Health Organization (WHO) 2008 classification of Lymphoma criteria or according to the recommendation of the Splenic Lymphoma Group for non splenectomized patient.
• If patients not splenectomised: diagnosis on bone marrow biopsy (histology and immunohistochemistry), and blood (cytology, immunophenotype), chromosomal abnormalities by QMPSF optional.
• 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 mono corticotherapy.
• Patients requiring a treatment with at least one of the following situation:
• Symptomatic SMZL in not splenectomized patients
• 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
• One of the following symptomatic/progressive cytopenias: Hb \<10 g/dL, or Plat \<80.000/mm3, or ANC \<1.000/mm3, whatever the reason (autoimmune or hypersplenism or bone marrow infiltration) not eligible for splenectomy or not willing splenectomy
• SMZL with enlarged lymphoadenopathy or involvement of extranodal sites with or without cytopenia
• Symptomatic disease in SMZL splenectomised patients with rapidly raising lymphocyte counts, development of lymphadenopathy or involvement of extranodal sites.
• SMZL with concomitant hepatitis C infection who have not responded or are relapsed after Interferon and/or Ribavirin.
• Clinically and/or radiologically confirmed measurable disease before treatment start.
• Aged ≥ 18 yo at time of initial diagnosis and ≤ 80 yo.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Minimum life expectancy of \>6 months.

You may not qualify if:

• 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.
• Uncontrolled hypertension.
• Uncontrolled diabetes mellitus as defined by the investigator.
• Active systemic infection requiring treatment.
• Previously known 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 ng/mL if they did not undergo prostatectomy.
• Impaired renal function with creatinine clearance \<10 ml/min.
• Severe chronic obstructive pulmonary disease with hypoxemia.
• Medical condition requiring long-term use (\>1 months) of systemic corticosteroids.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Sponsors & Collaborators

• International Extranodal Lymphoma Study Group (IELSG): lead

Study Sites (30)

Créteil (Hôpital Henri Mondor)

Créteil, France

Location

Dijon (CHU de Dijon - Hôpital d'Enfants)

Dijon, France

Location

Grenoble cedex 9 (CHU Michallon)

Grenoble, France

Location

Le Kremlin Bicêtre (Hôpital Bicêtre)

Le Kremlin-Bicêtre, France

Location

Le Mans (C.H. Le Mans)

Le Mans, France

Location

Lille cedex (CHRU Lille - Hôpital Claude Huriez)

Lille, France

Location

Pierre Bénite

Lyon Sud, France

Location

Vandoeuvre-les-Nancy cedex (CHU Brabois)

Nancy, France

Location

Nantes cedex 01 (CHU de Nantes - Hôtel Dieu)

Nantes, France

Location

Paris cedex 10 (Hôpital Saint-Louis)

Paris, France

Location

Pessac cedex (Centre François Magendie)

Pessac, France

Location

Rouen (Centre Henri Becquerel)

Rouen, France

Location

Ospedale Civile Ss. Antonio E Biagio

Alessandria, Italy

Location

A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona

Ancona, Italy

Location

Ospedale Armando Businco

Cagliari, Italy

Location

A.O. Universitaria S. Martino Di Genova

Genova, Italy

Location

Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Sede Di Meldola (Fc)

Meldola, Italy

Location

Irccs Fondazione Centro S. Raffaele Del Monte Tabor

Milan, Italy

Location

A.O. Universitaria Policlinico Di Modena

Modena, Italy

Location

A.O. "V. Cervello"

Palermo, Italy

Location

A.O. Universitaria Policlinico Giaccone

Palermo, Italy

Location

A.O. Universitaria Di Parma

Parma, Italy

Location

Ausl Di Piacenza

Piacenza, Italy

Location

Ospedale S. Maria Delle Croci Di Di Ravenna

Ravenna, Italy

Location

Ospedale Bianchi - Melacrino - Morelli

Reggio Calabria, Italy

Location

Ospedale Di S. Maria Nuova-Irccs

Reggio Emilia, Italy

Location

Irccs Centro Di Riferimento Oncologico Di Basilicata (Crob)

Rionero Sannitico, Italy

Location

Irccs Istituto Dermatologico S. Gallicano (Ifo)

Roma, Italy

Location

Azienda Ospedaliera "S. Maria"

Terni, Italy

Location

Ospedale Di Circolo E Fondazione Macchi

Varese, Italy

Location

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Emilio Iannitto
• Organization: U.O.C. Haematology - A.O.U. Policlinico Paolo Giaccone, Palermo (Italy)

emilio.iannitto@gmail.com

+39 091 6554415

Study Officials

• Emilio Iannitto, MD

  Presidio ospedaliero G. Moscati; UOC di Ematologia - Taranto

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: August 2, 2016
• Study Start: July 1, 2012
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: February 1, 2023
• Results First Posted: February 1, 2023

Record last verified: 2022-05

Locations

IT (18); FR (12)