Assessment of Efficacy and Safety of Front-line Fludarabine, Cyclophoshamide and Ofatumumab Chemoimmunotherapy in Young Patients With Chronic Lymphocytic Leukemia. (CLL0911)

• Number of complete responses. [ Time Frame: After 8 months from study entry. ] [ Designated as safety issue: No ]
  The complete response (CR) rate after FCO2 front-line treatment.
  
  

• Number of overall responses. [ Time Frame: After 8 months from study entry. ] [ Designated as safety issue: No ]
  Overall Response (OR) rate after FCO2 front-line treatment.
  
  
• Number of patients in progression-free survival. [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: No ]
  Progression-free survival (PFS) calculated from the date of first treatment dose - induction phase - until the date of the first documentation of progressive disease or until death (whatever the cause), whichever occurs first. Patients still alive and known to be progression free will be censored at the moment of last follow-up.
  
  
• Number of patients needing a new CLL Treatment. [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: No ]
  Time to a new CLL treatment (TTT) will be calculated from the date of last treatment dose until date of a new treatment received for CLL, where death occurred before the new treatment will be considered as competing risk. Patients still alive without receiving a new treatment will be censored at the time of the last follow-up.
  
  
• Number of patients in overall survival [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: No ]
  Overall survival (OS): defined as the time interval between the date of first treatment dose - induction phase- and the date of death for any cause; patients still alive will be censored at the moment of last follow-up.
  
  
• Number of toxic events. [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: Yes ]
  Toxicity of treatment according the last NCI criteria.
  
  
• Outcome of patients according to clinical and biologica variables. [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: No ]
  Outcome of patients (response, PFS OS) according to clinical and biologic variables (age; size of nodes, 2-microglobulin, lymphocyte count, stage, IgVH, p53, FISH, ZAP-70, CD38, FLCs).
  
  

Given that:

• rituximab, fludarabine and cyclophosphamide (FCR) front-line treatment was associated with a high OR rate, superior PFS and OS as compared to fludarabine and cyclophosphamide regimen;
• a direct relationship between the dose of rituximab and the response rate has been reported;
• ofatumumab, as single agent, proved activity in CLL patients with refractory disease;
• ofatumumab, fludarabine and cylophosphamide (O-FC) front-line treatment has been associated with a high complete response (CR) rate;
• the expected grade 3-4 granulocytopenia could led to reduce the dose intensity of study drugs (FC) and increase the infection rate; a schedule combining FC with an increased dose of ofatumumab associated to primary phrophylaxis of granulocytopenia could be associated with an improvement in the CR rate. The purpose of this study is to determine whether we could improve the CR rate of the golden standard treatment for fit patients with CLL , the FCR regimen, with a chemoimmunotherapy including FC combined with an increased dose of the monoclonal antibody ofatumumab, given every other week (FCO2) associated with a primary prophylaxis of granulocytopenia.