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 Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Rituximab Fludarabine Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab, Fludarabine, ciclophosphamide<br>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<br>* 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)<br>* Other names: GENOXAL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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R F C treatment in patients with Non Hodgkin Lymphoma