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; Blasio, Angelo De; Zaccaria, Alfonso; Morra, Enrica

doi:10.1182/blood-2011-05-351833

Cited by 27 publications

(17 citation statements)

References 25 publications

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“…The OR for all patients was 62%. This rate was comparable with that achieved in pretreated patients within the REACH trial with the FCR regimen and with FC plus alemtuzumab (OR: 69.9% and 67%, respectively) [27,28], and higher than that reported for alemtuzumab monotherapy (OR: 34%) [5]. It is noteworthy that the REACH trial did not include fludarabinerefractory patients, and the 17p deletion was present in only 7% of the patients.…”

Section: Discussionsupporting

confidence: 71%

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

et al. 2013

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Treatment of patients with B-cell chronic lymphocytic leukemia (CLL) relapsed/refractory (R/R) to conventional treatments is particularly challenging. The combination of bendamustine and cytarabine has demonstrated distinct and synergistic mechanisms of action in preclinical studies on cell lines and primary tumor cells of several B-cell lymphomas, including 17p deleted or TP53 mutated CLL. The efficacy of rituximab (375 mg/m 2 , Day 1), plus bendamustine (70 mg/m 2 , days 1-2), and cytarabine (800 mg/m 2 , Day 1-3; R-BAC), every 28 days for up to four courses, was evaluated in a pilot trial enrolling 13 patients with very selected high-risk R/R CLL. All patients (median age 60 years, range 53-74) had symptomatic Binet stage B or C active disease requiring treatment, were characterized by adverse cytogenetics (17p deletion, 11q deletion, or both), unmutated immunoglobulin heavy-chain variable region, and were heavily pretreated (1-5, median three previous lines). Overall, R-BAC was well tolerated with limited non-hematological toxicity. Major toxicities were transient Grade 3/4 neutropenia and thrombocytopenia in 84% and 85% of patients, respectively. Overall response rate (OR) was 84%, including complete and partial response in 38% and 46% of patients, respectively. Patients with 17p deletion had an OR of 78%. After a median follow-up of 17 months, median progression-free survival was 16 months while median overall survival (OS) was not reached (1-year OS: 75 6 13%). R-BAC is an active regimen in R/R heavily pretreated high-risk patients with CLL, representing an option for the treatment of patients that are usually refractory to standard therapy. Am. J.

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Section: Discussionsupporting

confidence: 71%

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

et al. 2013

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“…1* Alessandra Tedeschi, 1* Gianluca Gaidano, 2 Marta Coscia, 3 Valeria Belsito Petrizzi, 4 Ester Orlandi,…”

Section: Marco Montillounclassified

“…1 Higher response rates have been achieved when combined with fludarabine and cyclophosphamide (FC), but this regimen has led to some safety challenges both in first-line and relapsed settings. [2][3][4] Compared to FC, bendamustine shows a better safety profile, including a lower rate of myelosuppression and infective complications, [5][6][7] and was found to be an ideal chemotherapy approach to be investigated in combination with alemtuzumab (BenCam). We conducted an Italian multicenter, single arm, open label, phase I/II study in relapsed and refractory CLL to define the efficacy and tolerability of the combination intravenous (IV) bendamustine Days 1 and 2, and subcutaneous (SC) alemtuzumab Days 1-3, following at least one line of treatment including alkylating agents or purine analogs, alone or in combination.…”

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confidence: 99%

Bendamustine and subcutaneous alemtuzumab combination is an effective treatment in relapsed/refractory chronic lymphocytic leukemia patients

et al. 2014

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“…Fludarabine plus alemtuzumab yielded clearly better response rates and improved OS than fludarabine monotherapy. 61 Although high response rates have been achieved with the combination of alemtuzumab-fludarabine plus cyclophosphamide in relapsed and refractory patients, 62 experiences with this combination in the first-line setting have led to some safety challenges. A randomized study for untreated CLL patients by the French group comparing the activity of alemtuzumabfludarabine plus cyclophosphamide to rituximab-fludarabine plus cyclophosphamide was prematurely closed due to the excess of toxicity in the arm with the alemtuzumab combination.…”

Section: Alemtuzumabmentioning

confidence: 99%

Monoclonal Antibodies in Chronic Lymphocytic Leukemia

2016

Lymphoma and Chronic Lymphocytic Leukemias

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Monoclonal antibodies (MoAbs) play a pivotal role in the treatment of chronic lymphocytic leukemia (CLL). Rituximab, a MoAb against CD20, was initially used as a single agent in the treatment of CLL before being incorporated into newer combination regimens. Integration of rituximab into chemotherapy regimens has led to an improvement in the response rate and overall survival when used in frontline therapy. Despite this, CLL remains an incurable disease, and treatment of relapsed CLL, particularly after failure of purine analog-based regimens, remains challenging. Technological advances relating to development of chimeric and humanized MoAbs are supporting the role of antibody-based regimens for many diseases, including CLL. Currently, MoAbs represent an integral component of CLL therapy. The antitumor efficacy of many therapeutic MoAbs can be potentially improved upon by their use in combination with new targeted therapy agents.

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

Cited by 27 publications

References 25 publications

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

Bendamustine and subcutaneous alemtuzumab combination is an effective treatment in relapsed/refractory chronic lymphocytic leukemia patients

Monoclonal Antibodies in Chronic Lymphocytic Leukemia

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