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

Asociacion Espanola de Hematologia y Hemoterapia

Status and phase: Completed; Phase 4

Conditions: Non Hodgkin Lymphoma

Treatments: Drug: Rituximab Fludarabine Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT01124526

LNHF-03.

04-0199 (Other Identifier)

2004/254 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 75 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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75 participants in 1 patient group

Rituximab, Fludarabine, ciclophosphamide

Experimental group

Description:

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)

Treatment:

Drug: Rituximab Fludarabine Cyclophosphamide