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Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02853370
Recruitment Status : Active, not recruiting
First Posted : August 2, 2016
Last Update Posted : May 14, 2020
Sponsor:
Information provided by (Responsible Party):
International Extranodal Lymphoma Study Group (IELSG)

Tracking Information
First Submitted Date  ICMJE July 26, 2016
First Posted Date  ICMJE August 2, 2016
Last Update Posted Date May 14, 2020
Actual Study Start Date  ICMJE July 2012
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2016)
CT-scan of organomegaly (spleen-liver-lymph nodes) [ Time Frame: up to 24 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
CT-scan of organomegaly (spleen-liver-limph nodes) [ Time Frame: up to 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma
Official Title  ICMJE Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma. The International Extranodal Lymphoma Study Group (IELSG) 36 Phase II Prospective Study
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.

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Marginal Zone B-cell Lymphoma
Intervention  ICMJE Drug: Bendamustine and Rituximab
Study Arms  ICMJE Experimental: Bendamustine and Rituximab

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)

Intervention: Drug: Bendamustine and Rituximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 28, 2016)
65
Original Actual Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

    1. If patients not splenectomised: diagnosis on bone marrow biopsy (histology and immunohistochemistry), 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 mono corticotherapy.
  • Patients requiring a treatment with at least one of the following situation:

    1. Symptomatic SMZL in not splenectomized patients

      1. 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
      2. 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
      3. SMZL with enlarged lymphoadenopathy or involvement of extranodal sites with or without cytopenia
    2. Symptomatic disease in SMZL splenectomised patients with rapidly raising lymphocyte counts, development of lymphadenopathy or involvement of extranodal sites.
    3. 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:

    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 upper limit of normal (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)

Exclusion Criteria:

  • 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 hepatitis B surface (HBS)+; in case of presence of antibody anti hepatitis B core antigen (HBC)+ and anti HBS+, controls should be organized according to guidelines of American Association for the Study of Liver Disease (AASLD) and European Association for the Study of the Liver (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 Prostate Specific Antigen(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 month) 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02853370
Other Study ID Numbers  ICMJE IELSG 36
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party International Extranodal Lymphoma Study Group (IELSG)
Study Sponsor  ICMJE International Extranodal Lymphoma Study Group (IELSG)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Emilio Iannitto, MD Presidio ospedaliero G. Moscati; UOC di Ematologia - Taranto
PRS Account International Extranodal Lymphoma Study Group (IELSG)
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP