Trial of Bendamustine And Rituximab for Patients With Previously Untreated Extranodal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Multicentric, Non-Randomized Phase 2 Trial of Bendamustine And Rituximab for Patients With Previously Untreated Extranodal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

The aim of the study is to assess the therapeutic activity and safety of the combination of Bendamustine and Rituximab in MALT lymphomas.

Primary endpoint:

• Event-free-survival (EFS) (failure or death from any cause) for all patients.

Secondary endpoints:

• Complete and partial remission rates for all patients
• Response duration (time to relapse or progression) for responder patients
• Progression-free-survival (PFS) (disease progression or death from lymphoma: for all patients
• Overall survival for all patients
• Acute and long-term toxicity

Study Overview

• Status: Completed
• Conditions: MALT LYMPHOMA
• Intervention / Treatment: Drug: Rituximab and Bendamustine

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28006
    • Hospital La Princesa
  • Madrid, Spain, 28033
    • Hospital MD Anderson
  • Murcia, Spain, 30008
    • Hospital Morales Meseguer
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Zaragoza, Spain, 50009
    • Hospital Clínico de Zaragoza "Lozano Blesa"
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Hospital Central de Asturias
  • Barcelona
    • Badalona, Barcelona, Spain, 08918
      • ICO-HOSPITAL GERMANS TRIAS I PUJOL
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • ICO-Hospital Durans i Reynals
    • Terrassa, Barcelona, Spain, 08221
      • Hospital Mútua de Terrassa
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Marques de Valdecilla
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Hospital Fundación Alcorcón
  • Mallorca
    • Palma de Mallorca, Mallorca, Spain, 07198
      • Hospital Son Llatzer
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clínica Universitaria Navarra
  • Tenerife
    • Sta. Cruz de Tenerife, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type arisen at any extranodal site (WHO classification)
2. Any stage (Ann Arbor I-IV)

3. The novo disease en any extranodal site. For primary gastric or cutaneous lymphoma, local/specific previous treatment is accepted, just following the below criteria:

   1. Cutaneous lymphoma: recurrent lymphoma after local therapy
   2. Gastric lymphoma:

   b1. H. pylori-negative cases, either de novo (non pre-treated) or at relapse following local therapy (i.e., surgery, radiotherapy or antibiotics).

   b2. H. pylori-positive cases at diagnosis, who failed antibiotic therapy, including patients with: clinical (endoscopic) and histological evidence of disease progression at any time post H. pylori eradication; stable disease with persistent lymphoma at 1 year post H. pylori eradication; relapse (without H. pylori re-infection), after a remission; patients who failed either first line antibiotics or further local treatment (surgery or radiotherapy)

4. No evidence of histologic transformation to a high grade lymphoma
5. Measurable or evaluable disease
6. Age >18 and <85
7. ECOG performance status 0-2
8. Life expectancy of at least 1 year
9. Written informed consent given according to national/local regulations

Exclusion Criteria:

1. Prior chemotherapy or prior immunotherapy with any anti-CD20 monoclonal antibody
2. Prior radiotherapy in the last 6 weeks
3. Corticosteroids during the last 28 days, unless prednisone chronically administered at a dose <20 mg/day for indications other than lymphoma or lymphoma-related symptoms
4. Major impairment of renal function (serum creatinine > 2,5 x upper normal) or liver function (ASAT/ALAT <2,5 x upper normal, total bilirubin <2,5x upper normal), unless due to lymphoma involvement.
5. Impairment of bone marrow function (WBC <3.0x109/L, ANC <1.5x109/L, PLT <100x109/L), unless due to lymphoma involvement
6. Evidence of clinically significant cardiac, neurological or metabolic disease, unless due to lymphoma involvement
7. Evidence of symptomatic central nervous system (CNS) disease
8. Active HBV and/or HCV infection
9. Known HIV infection
10. Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer
11. Any psychiatric disease potentially hampering compliance with the study protocol and follow-up schedule
12. Potential to attend regular visits to the hospital, on an outpatient regimen
13. Hypersensibility to any compound of the study medication.
14. Non appropriate contraceptive method in women of childbearing potential or men
15. Treatment with any drug under research within 30 days previous to start the study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Rituximab and Bendamustine	Drug: Rituximab and Bendamustine; Rituximab 375 mg/m2 iv. day 1 Bendamustine 90 mg/m2 iv. day 1 and 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint of assessment is the event-free-survival (EFS) according to the criteria of the International Workshop to Standardize Response Criteria for NHL and Criteria for evaluation of response in NHL	2 years follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Include evaluation of the next parameters: Complete and partial remission rates for all patients Response duration for responder patients PFS for all patients Overall survival for all patients Acute and long-term toxicity	2 years follow-up

Collaborators and Investigators

• Sponsor: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
• Investigators: Principal Investigator: Carlos Montalbán, MD, Ramón y Cajal Hospital; Principal Investigator: Antonio Salar, MD, Hospital del Mar; Principal Investigator: Ana Muntañola, MD, Mutua de Terrassa Hospital; Principal Investigator: María José Terol, MD, Hospital Clínico de Valencia; Principal Investigator: Juan Manuel Sancho, MD, ICO Hospital Germans Trias i Pujol; Principal Investigator: Eva Domingo, MD, ICO Hospital Durans i Reynals; Principal Investigator: Grande Carlos, MD, 12 de Octubre Hospital; Principal Investigator: Carlos Panizo, MD, Clínica Universitaria Navarra; Principal Investigator: Raquel Oña, MD, MD Anderson Hospital; Principal Investigator: Reyes Arranz, MD, La Princesa Hospital; Principal Investigator: Dolores Caballero, MD, Hospital Unisversitario de Salamanca; Principal Investigator: José Luis Bello, MD, Complejo Hospitalario Universitario de Santiago; Principal Investigator: Luis Palomera, MD, Hospital Clínico de Zaragoza; Principal Investigator: Franciaco Javier Peñalver, MD, Fundacion Hospital Alcorcon; Principal Investigator: José Javier Sánchez-Blanco, MD, Morales Meseguer Hospital; Principal Investigator: Concepción Nicolás, MD, Central de Asturias Hospital

Publications and helpful links

General Publications

• Salar A, Domingo-Domenech E, Panizo C, Nicolas C, Bargay J, Muntanola A, Canales M, Bello JL, Sancho JM, Tomas JF, Rodriguez MJ, Penalver FJ, Grande C, Sanchez-Blanco JJ, Palomera L, Arranz R, Conde E, Garcia M, Garcia JF, Caballero D, Montalban C; Grupo Espanol de Linfomas/Trasplante de Medula Osea (GELTAMO). First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2014 Dec;1(3):e104-11. doi: 10.1016/S2352-3026(14)00021-0. Epub 2014 Nov 19.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: November 17, 2009
• First Submitted That Met QC Criteria: November 17, 2009
• First Posted (ESTIMATE): November 18, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): September 7, 2016
• Last Update Submitted That Met QC Criteria: September 6, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: CD 20 positive
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, B-Cell, Marginal Zone; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Bendamustine Hydrochloride; Rituximab
• Other Study ID Numbers: MALT2008-01; No EudraCT: 2008-007725-39