An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia

Marco Montillo, Alessandra Tedeschi, Valeria Belsito Petrizzi, Francesca Ricci, Monica Crugnola, Mauro Spriano, Pierangelo Spedini, Fiorella Ilariucci, Lilj Uziel, Immacolata Attolico, Eleonora Vismara, Angelo De Blasio, Alfonso Zaccaria, Enrica Morra

Research output: Contribution to journalArticle

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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/m 2 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.

Original languageEnglish
Pages (from-to)4079-4085
Number of pages7
JournalBlood
Volume118
Issue number15
DOIs
Publication statusPublished - Oct 13 2011

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B-Cell Chronic Lymphocytic Leukemia
Refractory materials
Cyclophosphamide
Labels
Cells
Cytotoxicity
Monoclonal Antibodies
Safety
Opportunistic Infections
Residual Neoplasm
Cytomegalovirus
Antibodies
Immunotherapy
Disease-Free Survival
Disease Progression
Anti-Idiotypic Antibodies
Therapeutics
fludarabine
alemtuzumab
Recurrence

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia. / Montillo, Marco; Tedeschi, Alessandra; Petrizzi, Valeria Belsito; Ricci, Francesca; Crugnola, Monica; Spriano, Mauro; Spedini, Pierangelo; Ilariucci, Fiorella; Uziel, Lilj; Attolico, Immacolata; Vismara, Eleonora; De Blasio, Angelo; Zaccaria, Alfonso; Morra, Enrica.

In: Blood, Vol. 118, No. 15, 13.10.2011, p. 4079-4085.

Research output: Contribution to journalArticle

Montillo, M, Tedeschi, A, Petrizzi, VB, Ricci, F, Crugnola, M, Spriano, M, Spedini, P, Ilariucci, F, Uziel, L, Attolico, I, Vismara, E, De Blasio, A, Zaccaria, A & Morra, E 2011, 'An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia', Blood, vol. 118, no. 15, pp. 4079-4085. https://doi.org/10.1182/blood-2011-05-351833
Montillo, Marco ; Tedeschi, Alessandra ; Petrizzi, Valeria Belsito ; Ricci, Francesca ; Crugnola, Monica ; Spriano, Mauro ; Spedini, Pierangelo ; Ilariucci, Fiorella ; Uziel, Lilj ; Attolico, Immacolata ; Vismara, Eleonora ; De Blasio, Angelo ; Zaccaria, Alfonso ; Morra, Enrica. / An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia. In: Blood. 2011 ; Vol. 118, No. 15. pp. 4079-4085.
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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/m 2 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.",
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AU - Petrizzi, Valeria Belsito

AU - Ricci, Francesca

AU - Crugnola, Monica

AU - Spriano, Mauro

AU - Spedini, Pierangelo

AU - Ilariucci, Fiorella

AU - Uziel, Lilj

AU - Attolico, Immacolata

AU - Vismara, Eleonora

AU - De Blasio, Angelo

AU - Zaccaria, Alfonso

AU - Morra, Enrica

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N2 - 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/m 2 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.

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