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

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

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.

Study Overview

• Status: Completed
• Conditions: Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: Rituximab Fludarabine Cyclophosphamide

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 Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to progression disease	42 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free-disease period		54 months
Overall survival		54 months
Safety of RFC	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.	54 months
Molecular monitoring of clinical response	Study of t14:18 translocation with altered expression of BCL2.	54 months

Collaborators and Investigators

• Sponsor: 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

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: May 14, 2010
• First Posted (Estimate): May 17, 2010

Study Record Updates

• Last Update Posted (Estimate): May 17, 2010
• Last Update Submitted That Met QC Criteria: May 14, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: R F C treatment in patients with Non Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab; Fludarabine
• 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)