Safety and Efficacy of Fludarabine and Cyclophosphamide + Rituximab

Follicular Lymphoma Clinical Trial

Official title:

Phase II Study of Rituximab in Combination With Fludarabine and Cyclophosphamide for the Treatment of Relapsed Follicular Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00393107
• Other study ID #: FR2
• Secondary ID: FolRec02GislFR2
• Status: Completed
• Phase: Phase 2
• First received: October 25, 2006
• Last updated: October 25, 2006
• Start date: March 2000
• Est. completion date: August 2006

Study information

• Verified date: October 2006
• Source: Gruppo Italiano Studio Linfomi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Bioethics Committee
• Study type: Interventional

Clinical Trial Summary

Purpose of this study was to assess the safety profile and the anti-lymphoma activity of the FC+R combination.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

• measurable disease

• 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

Exclusion Criteria:

• known HIV infections

• Known Hepatitis B or C

• CNS lymphoma

• previous malignancies, or cardiac, renal, hepatic, or respiratory failure

• Pregnant or lactating women and patients of child bearing potential unless using birth control measures

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

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• rituximab

• rituximab,fludarabine, cyclophosphamide

Locations

Country	Name	City	State
Italy	Ospedale di Arezzo	Arezzo
Italy	Ospedale Maggiore di Milano	Milano
Italy	Ospedale Monteluce	Perugia
Italy	Ospedale di Pescara	Pescara
Italy	Ospedale di Piacenza	Piacenza
Italy	Ospedale di Pisa	Pisa
Italy	Ospedale di Reggio Calabria	Reggio Calabria
Italy	Ospedale S. Maria Nuova	Reggio Emilia
Italy	Ospedale Molinette	Torino

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Studio Linfomi

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity during the treatment period
Primary	Efficacy evaluated in terms of complete and partial response 1 month after the end of therapy
Secondary	Efficacy evaluated in terms of molecular response ( bone marrow Bcl2 negativity after treatment)

External Links

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