Retrospective Study: Efficacy and Safety of Chlorambucil + Rituximab in CLL Patients
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|ClinicalTrials.gov Identifier: NCT01862445|
Recruitment Status : Unknown
Verified March 2018 by Gruppo Italiano Malattie EMatologiche dell'Adulto.
Recruitment status was: Active, not recruiting
First Posted : May 24, 2013
Last Update Posted : March 22, 2018
|Condition or disease|
|CLL B-cell Small Lymphocytic Lymphoma Untreated B-CLL Elderly Patients|
Illness: treatment overview Chronic lymphocytic leukemia (B-CLL) is the most prevalent adult leukemia among western countries (6.7% Non-Hodgkin Lymphomas- NHL). The incidence rate is 2-6 cases per 100.000 person per year increasing with age and reaching an incidence rate of about 13/100.000 at 65 years, median age of onset of the disease. There are two clinical staging systems currently in use for CLL (Rai and Binet staging systems) allowing a rough division of patients into three prognostic groups: good, intermediate and poor prognosis. The clinical course ranges from an indolent behaviour (Rai 0, Binet A) with a long term survival to an aggressive disease with a median survival of 2 years (Rai III and IV, Binet C). There is non survival benefit associated with an early therapy (Binet stage A and B). Treatment usually is initiated when patient progress to the advanced stage (Binet stage C) and/or become symptomatic (fever, night sweats, weight loss). Purine-analogues based chemo-immunotherapy regimens are now considered the standard of care for fit patient with B-CLL (Fludarabine-Cyclophosphamyde-Rituximab, FCR regimen). But aging of the host and biological features of the disease are critical issues in the choice of therapy. The FCR regimen can result in significant myelosuppression and a high rate of early and late infections, especially in elderly patients with B-CLL, suggesting that it may be too toxic and therefore unsuitable for the large subpopulation of elderly and comorbid patients affected by B-CLL/SLL.
Rationale Chlorambucil, an alkylating agent, was the standard first line treatment for B-CLL/SLL before the development of the purine analogues and monoclonal antibodies. Later, phase III trials showed an improved ORR and a prolongation of PFS with fludarabine alone. A further improvement was obtained with the addition of Cyclophosphamide to Fludarabine. Eventually, Fludarabine in combination with Cyclophosphamide and the monoclonal anti-CD20 antibody Rituximab became the standard first line therapy for CLL patients 18 to 65 years old. At the same time, the FCR regimen showed a significant rate of early toxicity consisting of myelosuppression and infection and also a high rate of late infection. Data showed by Hallek et al reported a rate of grade 3-4 hematological toxicity and total infections of 56% and 25%, respectively. They reported 8 treatment-related deaths (2%), five of these due to infections and 4 deaths occurring before the 3th cycle. Also has been reported by Tam et al a risk of 10% of late infection for the first year of remission after FCR treatment. Low-dose FCR was evaluated as an alternative option showing a lower rate of neutropenia, without reduction of response rate. Nevertheless, it was demonstrated to reduce the PFS and it has not been evaluated in the elderly or medically unfit population. Alternative treatments (i.e., low-dose fludarabine, low-dose fludarabine plus cyclophosphamide, rituximab alone) have been explored in phase II trials in elderly and/or medically unfit patients with CLL. Since the cohort sizes were small, however, no definitive recommendations could be made for clinical practice. About three-quarters of CLL patients are more than 65 years old. Data from the CLL 5 phase III trial of GCLLSG (German CLL study group) comparing fludarabine vs Chlorambucil in this setting of patients (median age 70 years, range 65-80 years) displayed no differences in OS and PFR between Fludarabine and Chl, despite a greater percentage of CR and ORR with Fludarabine. This suggests that in elderly B-CLL patients, Fludarabine alone does not represent a major benefit in respect of Chl as front-line therapy. However, rates of complete response (CR) with front-line Chlorambucil single agent are relatively low (up to 7%) as are overall responses (approximately 65%). Phase II trials are ongoing to investigate the efficacy and safety of Rituximab in combination with Chl in previously untreated patients affected by B-CLL.
|Study Type :||Observational|
|Estimated Enrollment :||100 participants|
|Official Title:||A Retrospective Study to Assess the Efficacy and Safety of Chlorambucil Plus Rituximab as Front-line Therapy in Elderly and/or Unfit Patients Affected by B-cell Chronic Lymphocytic Leukemia|
|Study Start Date :||October 2013|
|Estimated Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||May 2018|
Patients receiving Chlorambucil plus Rituximab
- Number of responding patients. [ Time Frame: 10 months from study entry ]Overall response rate.
- Number of adverse events. [ Time Frame: 24 months from study entry ]Safety of Rituximab and Chlorambucil regimen (type, frequency and severity).
- Number of days from the first dose of treatment to re-treatment. [ Time Frame: 24 months from study entry. ]Time to Re-Treatment (TTR) estimation starting from the date of the first dose of the study drug
- Number of patients surviving. [ Time Frame: 24 months from study entry. ]
Progression Free Survival (PFS) estimation starting from the date of the first dose of the study drug.
Overall Survival (OS) estimation starting from the date of the first dose of the study drug
- Number of patients in which the response and the biological and clinical characteristics of the disease at baseline are associated. [ Time Frame: After 10 months from study entry. ]Fitness status, FISH, IgVH, Zap70 and CD38.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01862445
|Study Chair:||Luca Laurenti, Dr.||Istituto di Ematologia, Università Cattolica del Sacro Cuore di Roma|