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Efficacy Response Duration and Toxicity of Rituximab, Fludarabine, and Cyclophosphamide (RFC) as 1st Line Treatment and Rituximab (R) in Maintenance Treatment in Follicular Non Hodgkin (FNH) Lymphoma

Phase 4
Completed
Conditions
Non Hodgkin Lymphoma
Interventions
Registration Number
NCT01124526
Lead Sponsor
Asociacion Espanola de Hematologia y Hemoterapia
Brief Summary

The purpose of this study is to determine whether the rituximab administration with fludarabine and cyclophosphamide results, are better, than the ones obtained with conventional therapy such as CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) and also to determine whether the rituximab administration as maintenance treatment during two years, increase the global clinical responses and the disease free time interval.

Detailed Description

The use of monoclonal antibodies, specifically the chimerical humanized anti-CD20 monoclonal antibody (Rituximab, MabThera®) represents one of the most innovative aspects in the indolent lymphoma treatment. Preliminary data show from 40% to 50% of response with a median response duration between 6 and 11 months in patients with relapsing FL. This response rate increase when rituximab is administered as initial treatment.

Therefore, not only due to the clinical results but also to the tolerance, and based on an innovative mechanism of action and in its minimal toxicity, it seems reasonable to raise the possibility to incorporate the administration of the monoclonal antibody with chemotherapeutic agents.

The development of a new treatment scheme that includes Rituximab administration within treatment protocols that combine fludarabine and cyclophosphamide, whose results are better than the ones obtained with conventional treatments such as CHOP, should increase the molecular response rate and contribute therefore to increase the disease-free time interval (time to progression), without adding any toxicity, in addition to achieve a higher proportion of clinical responses (as global as complete responses). In order to increase the time interval to progression, a maintenance treatment will be carried out for 2 years, which has shown an evident benefit in the time to progression in preliminary studies.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
75
Inclusion Criteria
  • Previously untreated patients with grade I-III follicular lymphoma (grade B- D from the Working Formulation, centrofollicular lymphoma in the REAL classification), without evidence of histological transformation.
  • Clinical diagnose by histological and/or immunophenotypical evaluation with positive results for CD 20 Mo Ab (node, bone marrow).
  • Ann-Arbor stage II-IV.
  • Male and female patients from 18 to 75 years old.
  • Lack of related clinically uncontrolled diseases.
  • Lack of VIH infection.
  • Performance status (ECOG) of 0, 1, 2.
  • Patients who voluntarily gave informed consent for the study participation.
  • Life expectancy > 3 months.
Exclusion Criteria
  • Pregnant or breast-feeding women.
  • Women of childbearing age who do not accept to use an effective contraceptive method during the treatment and one year post-treatment.
  • Immunodeficiency condition and autoimmune diseases.
  • Patients with advanced clinically uncontrolled cardiac, hepatic or renal insufficiency, defined by the following criteria: total bilirubin, alkaline phosphatase or transaminases >2 x upper limit of normal, and serum creatinine value >2 x upper limit of normal.
  • Patients previously treated with chemotherapy or radiotherapy.
  • History of oncologic disease within the last 5 years, apart from non-melanoma cutaneous neoplasia or carcinoma in situ of uterine cervix.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Rituximab, Fludarabine, ciclophosphamideRituximab Fludarabine CyclophosphamidePatients receiving from 4 to 6 cycles of chemotherapy (R F C) each 4 weeks depending on haematological tolerance: RITUXIMAB(R)375 mg/m2 iv,day 3 C1 and day 1 C2-C6,(total dose 375 mg/m2)
Primary Outcome Measures
NameTimeMethod
Time to progression disease42 months
Secondary Outcome Measures
NameTimeMethod
Free-disease period54 months
Overall survival54 months
Safety of RFC54 months

Toxicity is detailed and tabulate following the WHO classification. The safety analysis includes the incidence of adverse events (AE),vital signs and laboratory parameters.

Impact tables are made of AE following the classification of preferred term. Also include an analysis of the intensity of AE and their relation to the combiantion of study treatment.

Molecular monitoring of clinical response54 months

Study of t14:18 translocation with altered expression of BCL2.

Trial Locations

Locations (20)

Fundación Hospital Alcorcón

🇪🇸

Alcorcón, Madrid, Spain

Hospital Infanta Cristina

🇪🇸

Badajoz, Badajoz_Extremadura, Spain

Hospital Universitario Ramón y Cajal

🇪🇸

Madrid, Spain

Fundación Jiménez Díaz

🇪🇸

Madrid, Spain

Hospital Clínico San Carlos

🇪🇸

Madrid, Spain

Hospital Universitario Príncipe de Asturias

🇪🇸

Alcalá de Henares, Madrid, Spain

Hospital de Fuenlabrada

🇪🇸

Fuenlabrada, Madrid, Spain

Hospital San Pedro de Alcántara

🇪🇸

Cáceres, Cáceres_Extremadura, Spain

Hospital Clínico del Río Hortega

🇪🇸

Valladolid, Valladolid_Castilla León, Spain

Complejo Hospitalario Xeral_Calde

🇪🇸

Lugo, Lugo_ Galicia, Spain

Hospital Severo Ochoa

🇪🇸

Leganés, Madrid, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Hospital Clínico Universitario de Salamanca

🇪🇸

Salamanca, Salamanca_Castilla León, Spain

Hospital General de Segovia

🇪🇸

Segovia, Segovia_ Castilla León, Spain

Instituto Catalán de Oncología (ICO)

🇪🇸

Barcelona, Barcelona_Cataluña, Spain

Hospital del Mar

🇪🇸

Barcelona, Barcelona_ Cataluña, Spain

Hospital de Puerto Real

🇪🇸

Puerto Real, Cádiz_ Andalucía, Spain

Hospital de Móstoles

🇪🇸

Móstoles, Madrid, Spain

MD Anderson Internacional España

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

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