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

Sponsor

Asociacion Espanola de Hematologia y Hemoterapia (Other)

Overall Status

Completed

CT.gov ID

NCT01124526

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

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 :

Sep 1, 2004

Actual Primary Completion Date :

Jul 1, 2007

Actual Study Completion Date :

Jul 1, 2008

Arms and Interventions

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

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

Primary Outcome Measures

Time to progression disease [42 months]

Secondary Outcome Measures

Free-disease period [54 months]
Overall survival [54 months]
Safety of RFC [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.
Molecular monitoring of clinical response [54 months]
Study of t14:18 translocation with altered expression of BCL2.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Hospital Infanta Cristina	Badajoz	Badajoz_Extremadura	Spain	06080
2	Hospital del Mar	Barcelona	Barcelona_ Cataluña	Spain	08003
3	Instituto Catalán de Oncología (ICO)	Barcelona	Barcelona_Cataluña	Spain	08907
4	Hospital San Pedro de Alcántara	Cáceres	Cáceres_Extremadura	Spain	10003
5	Hospital de Puerto Real	Puerto Real	Cádiz_ Andalucía	Spain	11510
6	Complejo Hospitalario Xeral_Calde	Lugo	Lugo_ Galicia	Spain	27004
7	Hospital Universitario Príncipe de Asturias	Alcalá de Henares	Madrid	Spain	28805
8	Fundación Hospital Alcorcón	Alcorcón	Madrid	Spain	28922
9	Hospital de Fuenlabrada	Fuenlabrada	Madrid	Spain	28943
10	Hospital Severo Ochoa	Leganés	Madrid	Spain	28911
11	Hospital de Móstoles	Móstoles	Madrid	Spain	28935
12	Hospital Clínico Universitario de Salamanca	Salamanca	Salamanca_Castilla León	Spain	37007
13	Hospital General de Segovia	Segovia	Segovia_ Castilla León	Spain	40001
14	Hospital Clínico del Río Hortega	Valladolid	Valladolid_Castilla León	Spain	47010
15	MD Anderson Internacional España	Madrid		Spain	28033
16	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
17	Fundación Jiménez Díaz	Madrid		Spain	28040
18	Hospital Clínico San Carlos	Madrid		Spain	28040
19	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
20	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