AzTrials
AzTrials

Marginal Zone B-cell LymphomaPhase 2NCT02853370

Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma

A Phase 2 study testing Bendamustine and Rituximab in people with Marginal Zone B-cell Lymphoma, run by International Extranodal Lymphoma Study Group (IELSG) at 30 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Marginal Zone B-cell Lymphoma
What is being tested?
Bendamustine and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
30 sitesin 2 countries
Study dates
Jul 2012to Dec 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 25Show fewer
  • 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.
  • 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:
  • Absolute neutrophil count (ANC) ≥1.000/mm3 and Platelets ≥100.000/mm3, unless these abnormalities are related to bone marrow infiltration or to hypersplenism.
  • Aspartate transaminase (AST) ≤2 x upper limit of normal (ULN); Alanine transaminase (ALT) ≤2 x ULN; total bilirubin ≤1.5 x ULN.
  • Creatinine clearance ≥ 10 ml/min (as calculated by the Cockcroft-Gault formula)
  • All patients must:
  • Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
  • Agree not to share study medication with another person.
  • Agree to use an adequate method of contraception for women of childbearing potential during the study treatment and until 12 months after the end of the study treatment.
  • Agree to use an adequate method of contraception for men during the study treatment and until 6 months after the end of the study treatment

Who cannot join

  • 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.
Show all 19Show fewer
  • 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.
  • Major surgery within 30 days before the inclusion in the study
  • A positive Coombs test without haemolysis or an autoimmune hemolytic anemia is not an exclusion criterion.
  • 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.
  • Prior participation in another study with experimental drug during the last 4 months.
  • Pregnant or currently breast-feeding woman.

Trial locations and contacts

30 sites in 2 countries.

30 sites in 2 countries

Italy18 sites

  • Ospedale Civile Ss. Antonio E Biagio

    Alessandria

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

    Ancona

  • Ospedale Armando Businco

    Cagliari

  • A.O. Universitaria S. Martino Di Genova

    Genova

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

    Meldola

  • Irccs Fondazione Centro S. Raffaele Del Monte Tabor

    Milan

  • A.O. Universitaria Policlinico Di Modena

    Modena

  • A.O. "V. Cervello"

    Palermo

  • A.O. Universitaria Policlinico Giaccone

    Palermo

  • A.O. Universitaria Di Parma

    Parma

  • Ausl Di Piacenza

    Piacenza

  • Ospedale S. Maria Delle Croci Di Di Ravenna

    Ravenna

  • Ospedale Bianchi - Melacrino - Morelli

    Reggio Calabria

  • Ospedale Di S. Maria Nuova-Irccs

    Reggio Emilia

  • Irccs Centro Di Riferimento Oncologico Di Basilicata (Crob)

    Rionero Sannitico

  • Irccs Istituto Dermatologico S. Gallicano (Ifo)

    Roma

  • Azienda Ospedaliera "S. Maria"

    Terni

  • Ospedale Di Circolo E Fondazione Macchi

    Varese

Other trials in Italy

France12 sites

  • Créteil (Hôpital Henri Mondor)

    Créteil

  • Dijon (CHU de Dijon - Hôpital d'Enfants)

    Dijon

  • Grenoble cedex 9 (CHU Michallon)

    Grenoble

  • Le Kremlin Bicêtre (Hôpital Bicêtre)

    Le Kremlin-Bicêtre

  • Le Mans (C.H. Le Mans)

    Le Mans

  • Lille cedex (CHRU Lille - Hôpital Claude Huriez)

    Lille

  • Pierre Bénite

    Lyon Sud

  • Vandoeuvre-les-Nancy cedex (CHU Brabois)

    Nancy

  • Nantes cedex 01 (CHU de Nantes - Hôtel Dieu)

    Nantes

  • Paris cedex 10 (Hôpital Saint-Louis)

    Paris

  • Pessac cedex (Centre François Magendie)

    Pessac

  • Rouen (Centre Henri Becquerel)

    Rouen

Other trials in France

About this study

Official title: Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma. The International Extranodal Lymphoma Study Group (IELSG) 36 Phase II Prospective Study

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.

Read the detailed description

Prospective, multicenter, open-label, phase II study, designed to determine efficacy and safety of a Chemo-immunotherapy with the combination of bendamustine + rituximab in patients with splenic marginal zone lymphoma.

Study Population: previously untreated (except for splenectomy and/or antiviral therapy for Hepatitis C Virus (HCV) infection) and symptomatic Splenic Marginal Zone patients.

Objectives: evaluation of the efficacy and the safety of R-Bendamustine in symptomatic Splenic Marginal Zone Lymphoma patients.

Primary Objective: efficacy of R-Bendamustine measured by Complete Response rate. Complete response rate defined as regression to normal size on CT of organomegaly (spleen, liver, lymph nodes); normalization of the blood counts and no evidence of circulating clonal cells, and no evidence or minor (≤ 5%) Bone Marrow (BM) infiltration detected by immunohistochemistry (IHC).

Treatment: The R-Bendamustine regimen consisted of 28-day cycle. Patients achieving a complete response (CR) after 3 cycles received only one more cycle of R-Bendamustine, while those achieving a partial response (PR) received 3 additional cycles of R-Bendamustine; if less than PR patients were withdrawn from the study

Being tested
Bendamustine and Rituximab
Medical subject headings
Lymphoma, B-Cell, Marginal Zone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bendamustine and RituximabDrug

Study groups in NCT02853370
Study groupRoleWhat they receive
Bendamustine and RituximabExperimentalInduction 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)
Receives: Drug: Bendamustine and Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (7)

  1. Overall Response Rate (ORR)

    Percentage of patients with complete and partial response. Partial response (PR) requires regression of 50% or greater in the measurable disease manifestations and no new sites of disease.

    This should include: resolution or decrease in spleen size, improvement on cytopenias and resolution or decrease in lymphadenopathy if present. Bone Marrow should show a decrease in the level of lymphoid infiltration and improvement of the haemopoietic reserve

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

  2. 3-year Progression Free Survival (PFS)

    Percentage of patients free from disease progression after 3 years from study entry.

    Progression is defined as 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.

    Measured: 3 years after study entry

  3. 3-years Duration of Response (DOR)

    Percentage of responding patients after 3 years from study entry. DOR is defined for all patients who achieved a response (CR and PR)

    Measured: 3 years from study entry

  4. 3-years Event Free Survival (EFS)

    Percentage of patients free from events after 3 years from study entry. Events are defined as any treatment failure including disease progression, or discontinuation of treatment for any cause (eg, disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death).

    Measured: 3 years after study entry

  5. 3-years Overall Survival Rate

    Percentage of patients alive after 3 years from study entry

    Measured: 3 years after treatment start

  6. 5 Years Progression Free Survival (PFS) -

    Percentage of patients free from disease progression after 5 years from treatment start. Progression is defined as 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.

    Measured: Five years after study entry

  7. 5 Years Overall Survival (OS)

    Percentage of patients alive after 5 years from study entry

    Measured: Five years after study entry

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2016 (estimated)
  2. Study startJul 2012
  3. Primary completionDec 2020
  4. Study completionDec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02853370
Sponsor's protocol ID
IELSG 36
Status last verified
May 2022
First submitted
26 Jul 2016
Last updated
1 Feb 2023

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bendamustine and Rituximab in people with Marginal Zone B-cell Lymphoma, run by International Extranodal Lymphoma Study Group (IELSG) at 30 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Italy, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response Rate (CRR) (time frame: At the end of treatment (After 24 weeks of treatment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02853370.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in