title: An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia.
abstract: Although combination regimens have improved outcomes over monotherapy in chronic lymphocytic leukemia (CLL), patients eventually relapse. Combined fludarabine, cyclophosphamide, and monoclonal anti-CD52 antibody alemtuzumab (FCC) provided synergistic cytotoxicity with effective clearing of minimal residual disease. This phase 2 study determined FCC efficacy and safety in relapsed/refractory CD52(+) B-CLL after ≥ 1 line of treatment. From January 2005 through June 2008, up to 6 courses of oral fludarabine 40 mg/m² per day, oral cyclophosphamide 250 mg/m² per day, and subcutaneous alemtuzumab (Mab-Campath) 10 mg (increased to 20 mg after first 10-patient cohort) were administered days 1 to 3 every 28 days. The primary objective was overall response rate (ORR); secondary objectives included response duration, time to disease progression, and safety and tolerability. ORR was 67% in 43 patients; 30% achieved complete response. ORR significantly improved with 1 versus ≥ 2 prior therapies (P = .018), and without versus with previous monoclonal antibody treatment (P = .003). Median progression-free survival was 24.4 months, not reached in patients achieving complete response. Median overall survival was 33.6 months. Myelosuppression was the most common adverse event, with a low percentage of cytomegalovirus reactivations and manageable infections. However, close vigilance of opportunistic infections is warranted. FCC provides effective immunotherapy in relapsed/refractory CLL, including in patients with poor-risk prognostic factors.
authors.affiliation: Department of Oncology/Haematology, Niguarda Ca' Granda Hospital, Milano, Italy. marco.montillo@ospedaleniguarda.it
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
authors.forename: Valeria Belsito
authors.initials: VB
authors.lastname: Petrizzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.forename: Monica
authors.initials: M
authors.lastname: Crugnola
authors.forename: Mauro
authors.initials: M
authors.lastname: Spriano
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Spedini
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ilariucci
authors.forename: Lilj
authors.initials: L
authors.lastname: Uziel
authors.forename: Immacolata
authors.initials: I
authors.lastname: Attolico
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vismara
authors.forename: Angelo
authors.initials: A
authors.lastname: De Blasio
authors.forename: Alfonso
authors.initials: A
authors.lastname: Zaccaria
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D015996:Survival Rate; D013997:Time Factors; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine