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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Non Hodgkin Lymphoma	Drug: Rituximab Fludarabine Cyclophosphamide	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	75 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	September 2004
Actual Primary Completion Date :	July 2007
Actual Study Completion Date :	July 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Rituximab, Fludarabine, ciclophosphamide; Patients 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)	Drug: Rituximab Fludarabine Cyclophosphamide; Patients 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) FLUDARABINE(F):25 mg/m2 iv, day 1-3,(total dose 75 mg/m2) CICLOPHOSPHAMIDE(C)1000 mg/m2 iv, day 1,(total dose 1000 mg/m2); Other Names: MABTHERA; BENEFLUR; GENOXAL

Outcome Measures

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Primary Outcome Measures :

1. Time to progression disease [ Time Frame: 42 months ]

Secondary Outcome Measures :

1. Free-disease period [ Time Frame: 54 months ]
2. Overall survival [ Time Frame: 54 months ]
3. Safety of RFC [ Time Frame: 54 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.

4. Molecular monitoring of clinical response [ Time Frame: 54 months ]
   Study of t14:18 translocation with altered expression of BCL2.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Locations

Spain
Hospital Infanta Cristina
Badajoz, Badajoz_Extremadura, Spain, 06080
Hospital del Mar
Barcelona, Barcelona_ Cataluña, Spain, 08003
Instituto Catalán de Oncología (ICO)
Barcelona, Barcelona_Cataluña, Spain, 08907
Hospital San Pedro de Alcántara
Cáceres, Cáceres_Extremadura, Spain, 10003
Hospital de Puerto Real
Puerto Real, Cádiz_ Andalucía, Spain, 11510
Complejo Hospitalario Xeral_Calde
Lugo, Lugo_ Galicia, Spain, 27004
Hospital Universitario Príncipe de Asturias
Alcalá de Henares, Madrid, Spain, 28805
Fundación Hospital Alcorcón
Alcorcón, Madrid, Spain, 28922
Hospital de Fuenlabrada
Fuenlabrada, Madrid, Spain, 28943
Hospital Severo Ochoa
Leganés, Madrid, Spain, 28911
Hospital de Móstoles
Móstoles, Madrid, Spain, 28935
Hospital Clínico Universitario de Salamanca
Salamanca, Salamanca_Castilla León, Spain, 37007
Hospital General de Segovia
Segovia, Segovia_ Castilla León, Spain, 40001
Hospital Clínico del Río Hortega
Valladolid, Valladolid_Castilla León, Spain, 47010
MD Anderson Internacional España
Madrid, Spain, 28033
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034
Fundación Jiménez Díaz
Madrid, Spain, 28040
Hospital Clínico San Carlos
Madrid, Spain, 28040
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario La Paz
Madrid, Spain, 28046

Sponsors and Collaborators

Asociacion Espanola de Hematologia y Hemoterapia

Investigators

Study Director:	José F. Tomás, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	E . Prieto Pareja, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	F. Hernández Navarro, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	J. Díaz Mediavilla, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	C. Montalbán, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	F. Javier Peñañver, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	J. De La Serna, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	Mª Carmen Burgaleta, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	P. Sánchez Godoy, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	Mª Dolores Monteagudo, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	A. Fernández De Sevilla, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	Mª Jesús Peñarrubia, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	Mª Dolores Caballero Barrigón, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	R. Bajo Gómez, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	A. Paz Coll, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	J. A. Queizán, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	C. Cabrera Silva, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	O. Arija, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	P. Bravo Barahona, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Principal Investigator:	A. Salar, MD	Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	JF Tomás / MD, Asociación Española de Hematología y Hemoterapia
ClinicalTrials.gov Identifier:	NCT01124526 History of Changes
Other Study ID Numbers:	LNHF-03.; 04-0199 ( Other Identifier: Spanish Health Minyster (AEMPS) ); 2004/254 ( Other Identifier: Local Ethic Comities from Madrid CEIC_R MADRID )
First Posted:	May 17, 2010
Last Update Posted:	May 17, 2010
Last Verified:	May 2010

Keywords provided by Asociacion Espanola de Hematologia y Hemoterapia:

R F C treatment in patients with Non Hodgkin Lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cyclophosphamide; Fludarabine phosphate; Rituximab; Fludarabine; Vidarabine	Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents