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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

Primary Purpose

Non Hodgkin Lymphoma

Status

Completed

Phase

Phase 4

Locations

Spain

Study Type

Interventional

Intervention

Rituximab Fludarabine Cyclophosphamide

About this trial

This is an interventional treatment trial for Non Hodgkin Lymphoma focused on measuring R F C treatment in patients with Non Hodgkin Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab, Fludarabine, ciclophosphamide

Arm 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)

Outcomes

Primary Outcome Measures

Time to progression disease

Secondary Outcome Measures

Free-disease period

Overall survival

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.

Molecular monitoring of clinical response

Study of t14:18 translocation with altered expression of BCL2.

Full Information

NCT ID

NCT01124526

First Posted

February 10, 2009

Last Updated

May 14, 2010

Sponsor

Asociacion Espanola de Hematologia y Hemoterapia

1. Study Identification

Unique Protocol Identification Number

NCT01124526

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

May 2010

Overall Recruitment Status

Completed

Study Start Date

September 2004 (undefined)

Primary Completion Date

July 2007 (Actual)

Study Completion Date

July 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Asociacion Espanola de Hematologia y Hemoterapia

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non Hodgkin Lymphoma

Keywords

R F C treatment in patients with Non Hodgkin Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

75 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rituximab, Fludarabine, ciclophosphamide

Arm Type

Experimental

Arm 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)

Intervention Type

Drug

Intervention Name(s)

Rituximab Fludarabine Cyclophosphamide

Other Intervention Name(s)

MABTHERA, BENEFLUR, GENOXAL

Intervention 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) 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)

Primary Outcome Measure Information:

Title

Time to progression disease

Time Frame

42 months

Secondary Outcome Measure Information:

Title

Free-disease period

Time Frame

54 months

Title

Overall survival

Time Frame

54 months

Title

Safety of RFC

Description

Time Frame

54 months

Title

Molecular monitoring of clinical response

Description

Study of t14:18 translocation with altered expression of BCL2.

Time Frame

54 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials: