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

Non Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01124526
• Other study ID #: LNHF-03.
• Secondary ID: 04-01992004/254
• Status: Completed
• Phase: Phase 4
• First received: February 10, 2009
• Last updated: May 14, 2010
• Start date: September 2004
• Est. completion date: July 2008

Study information

• Verified date: May 2010
• Source: Asociacion Espanola de Hematologia y Hemoterapia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: July 2008
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

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)

Locations

Country	Name	City	State
Spain	Hospital Universitario Príncipe de Asturias	Alcalá de Henares	Madrid
Spain	Fundación Hospital Alcorcón	Alcorcón	Madrid
Spain	Hospital Infanta Cristina	Badajoz	Badajoz_Extremadura
Spain	Hospital del Mar	Barcelona	Barcelona_ Cataluña
Spain	Instituto Catalán de Oncología (ICO)	Barcelona	Barcelona_Cataluña
Spain	Hospital San Pedro de Alcántara	Cáceres	Cáceres_Extremadura
Spain	Hospital de Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Severo Ochoa	Leganés	Madrid
Spain	Complejo Hospitalario Xeral_Calde	Lugo	Lugo_ Galicia
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	MD Anderson Internacional España	Madrid
Spain	Hospital de Móstoles	Móstoles	Madrid
Spain	Hospital de Puerto Real	Puerto Real	Cádiz_ Andalucía
Spain	Hospital Clínico Universitario de Salamanca	Salamanca	Salamanca_Castilla León
Spain	Hospital General de Segovia	Segovia	Segovia_ Castilla León
Spain	Hospital Clínico del Río Hortega	Valladolid	Valladolid_Castilla León

Sponsors (1)

Lead Sponsor	Collaborator
Asociacion Espanola de Hematologia y Hemoterapia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression disease		42 months	Yes
Secondary	Free-disease period		54 months	Yes
Secondary	Overall survival		54 months	Yes
Secondary	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	Yes
Secondary	Molecular monitoring of clinical response	Study of t14:18 translocation with altered expression of BCL2.	54 months	Yes