Clinical trial NCT01124526: 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
Official title: Prospective Non-randomized Multicenter Study to Assess the Efficacy Response Duration and Toxicity of RFC as First-line Treatment and R as Maintenance Treatment, in Patients Diagnosed of Follicular Non Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non Hodgkin Lymphoma
Keywords: R F C treatment in patients with Non Hodgkin Lymphoma
Lead sponsor: Asociacion Espanola de Hematologia y Hemoterapia
Sponsor class: OTHER
First posted: 2010-05-17
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to progression disease
timeFrame: 42 months
Secondary outcomes:
measure: Free-disease period
timeFrame: 54 months
measure: Overall survival
timeFrame: 54 months
measure: Safety of RFC
timeFrame: 54 months
measure: Molecular monitoring of clinical response
timeFrame: 54 months
Other outcomes:
Locations:
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
state: Badajoz_Extremadura
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Barcelona_ Cataluña
city: Barcelona
country: Spain
facility: Instituto Catalán de Oncología (ICO)
state: Barcelona_Cataluña
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
state: Cáceres_Extremadura
city: Puerto Real
country: Spain
facility: Hospital de Puerto Real
state: Cádiz_ Andalucía
city: Lugo
country: Spain
facility: Complejo Hospitalario Xeral_Calde
state: Lugo_ Galicia
city: Alcalá de Henares
country: Spain
facility: Hospital Universitario Príncipe de Asturias
state: Madrid
city: Alcorcón
country: Spain
facility: Fundación Hospital Alcorcón
state: Madrid
city: Fuenlabrada
country: Spain
facility: Hospital de Fuenlabrada
state: Madrid
city: Leganés
country: Spain
facility: Hospital Severo Ochoa
state: Madrid
city: Móstoles
country: Spain
facility: Hospital de Móstoles
state: Madrid
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
state: Salamanca_Castilla León
city: Segovia
country: Spain
facility: Hospital General de Segovia
state: Segovia_ Castilla León
city: Valladolid
country: Spain
facility: Hospital Clínico del Río Hortega
state: Valladolid_Castilla León
city: Madrid
country: Spain
facility: MD Anderson Internacional España
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: José F. Tomás, MD
role: STUDY_DIRECTOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: E . Prieto Pareja, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: F. Hernández Navarro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: J. Díaz Mediavilla, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: C. Montalbán, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: F. Javier Peñañver, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: J. De La Serna, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: Mª Carmen Burgaleta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: P. Sánchez Godoy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: Mª Dolores Monteagudo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: A. Fernández De Sevilla, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: Mª Jesús Peñarrubia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: Mª Dolores Caballero Barrigón, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: R. Bajo Gómez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: A. Paz Coll, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: J. A. Queizán, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: C. Cabrera Silva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: O. Arija, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: P. Bravo Barahona, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
name: A. Salar, MD
role: PRINCIPAL_INVESTIGATOR
References: