Safety and Efficacy of Fludarabine and Cyclophosphamide + Rituximab
Purpose of this study was to assess the safety profile and the anti-lymphoma activity of the FC+R combination.
|Condition or Disease||Intervention/Treatment||Phase|
The natural history of follicular lymphomas is characterized by a high initial response rate to chemotherapy followed invariably by relapse, with subsequent remissions of progressively shorter duration. The majority of patients eventually die of their disease. As yet, there is no gold standard for the treatment of newly diagnosed or relapsed advanced FL.Rituximab(R) has been shown to be a highly effective agent in the treatment of FL, either alone or in combination with chemotherapy. The ability of R to sensitize indolent lymphoma derived cell lines to cytotoxic chemotherapy agents has been demonstrated. Furthermore, fludarabine (F) may also sensitize cells to the effects of R. Cyclophosphamide (C) and F have shown in vivo synergistic activity. In view of the single agent activity and demonstrated synergy between C and F, and between F and R, we evaluated FC+R in previously treated patients with advanced FL. The primary aim of this study was to assess the safety profile and clinical activity of the FC+R combination. The secondary goal was to evaluate the ability of the treatment to convert bone marrow Bcl2 positivity such that patients achieved molecular remissions.
Primary Outcome Measures
- Toxicity during the treatment period 
- Efficacy evaluated in terms of complete and partial response 1 month after the end of therapy 
Secondary Outcome Measures
- Efficacy evaluated in terms of molecular response ( bone marrow Bcl2 negativity after treatment) 
histologically documented WHO grade 1-2 ,CD20+,follicular lymphoma
relapsed Follicular lymphoma
stage III or IV disease
Stage II patients are eligible if they present with B symptoms or bulky disease
to have a need for therapy in the opinion of treating clinician
expected survival of 6 months or more
age 18 to 70 years
to have undergone < 3 lines of chemotherapy
performance status of 0 to 2
known HIV infections
Known Hepatitis B or C
previous malignancies, or cardiac, renal, hepatic, or respiratory failure
Pregnant or lactating women and patients of child bearing potential unless using birth control measures
Contacts and Locations
|1||Ospedale di Arezzo||Arezzo||Italy||52100|
|2||Ospedale Maggiore di Milano||Milano||Italy||20100|
|4||Ospedale di Pescara||Pescara||Italy||89100|
|5||Ospedale di Piacenza||Piacenza||Italy||29100|
|6||Ospedale di Pisa||Pisa||Italy||56100|
|7||Ospedale di Reggio Calabria||Reggio Calabria||Italy||89100|
|8||Ospedale S. Maria Nuova||Reggio Emilia||Italy||42100|
Sponsors and Collaborators
- Gruppo Italiano Studio Linfomi
- Principal Investigator: Sacchi Stefano, MD, GISL
Study Documents (Full-Text)None provided.
- Alas S, Bonavida B. Rituximab inactivates signal transducer and activation of transcription 3 (STAT3) activity in B-non-Hodgkin's lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of Bcl-2 and sensitization to cytotoxic drugs. Cancer Res. 2001 Jul 1;61(13):5137-44.
- Alas S, Emmanouilides C, Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. Clin Cancer Res. 2001 Mar;7(3):709-23.
- Bellosillo B, Villamor N, Colomer D, Pons G, Montserrat E, Gil J. In vitro evaluation of fludarabine in combination with cyclophosphamide and/or mitoxantrone in B-cell chronic lymphocytic leukemia. Blood. 1999 Oct 15;94(8):2836-43.
- Di Gaetano N, Xiao Y, Erba E, Bassan R, Rambaldi A, Golay J, Introna M. Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone. Br J Haematol. 2001 Sep;114(4):800-9.
- Sacchi S., Tucci A, Merli F, Orsucci L, Cervetti G, Occhini U, Liberati M, Tarantini G, Callea V, Brugiatelli M, Lauta VM, Baldini L, Luminari S, Federico M. Dipartimento di Oncologia ed Ematologia,. Phase II Study with Fludarabine and Cyclophosphamide Plus Rituximab (FC+R) in Relapsed Follicular Lymphoma Patients. ASH 2002. Blood 99, 2002 Ab n° 530