R-2cda and Prolongation of Therapy With Rituximab Alone in Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma
R-2cda and Prolongation of Therapy With Rituximab Alone in Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma
The objective of this study is to confirm the efficacy of the association of R-2cda in
 patients affected by Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma and of
 evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab
 alone in increasing and prolonging the duration of the response.
Chronic Lymphocytic Leukaemia (CLL) is a lymphoproliferative disorder characterized by the
 progressive accumulation of monoclonal peripheral B cells in bone marrow, peripheral blood
 and lymphoid tissues. Median survival is about 10 years. It is now clear that front line
 therapy for a patient with CLL requiring treatment should be the association of purine
 analogue and rituximab with or without cyclophosphamide. Concerning the choice of the purine
 analogue, similar results have been obtained by using cladribine instead of fludarabine.
 Although cladribine is less commonly used, the direct comparison between the two analogues
 for what concerns efficacy and toxicity, has confirmed the same profile of the two drugs.
 Encouraging results have been obtained using the monoclonal antibody in association with the
 purine analogue.

 The utilization of rituximab as a maintenance therapy could improve the response in cases of
 persistence of minimal residual disease as well as delay the insurgence of relapses thus
 increasing the DFS.

 The objective of this study is to confirm the efficacy of the association of R-2cda and of
 evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab
 alone in increasing and prolonging the duration of the response. The results of this study
 will be compared with existing clinical results from a group of 42 pts already treated as
 standard with R-2cda without additional rituximab infusions.

 Patients enrolled in the study will receive 4 cycles of R-2-CdA therapy. Patients, who
 achieve a partial response or complete response after the therapy with R- 2-CdA, will prolong
 therapy with Rituximab. The therapy will begin 3 months after the end of the induction
 therapy and patients will receive one administration every 2 months for a total of 8
 administrations.
Inclusion Criteria:

 -  Aged ≥ 18 years

 -  Patients affected by CLL / SLL

 -  Presence of active disease defined as the presence of one of the following:

 Disease related symptoms (weight loss >10% in the last 6 months, fever >38° C for 2 weeks
 without evidence of infection, or marked asthenia, or profuse sweating without evidence of
 infection) Massive nodes (at least 10 cm in longest diameter) or progressive or symptomatic
 lymphadenopathy Massive (at least 6 cm below left costal margin) or progressive or
 symptomatic splenomegaly Progressive lymphocytosis (increased >50% in 2 months) or
 lymphocyte doubling time < 6 months Evidence of progressive bone marrow insufficiency seen
 as evidence of or worsening of anemia and or thrombocytopenia Autoimmune anemia and or
 thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy

 Exclusion Criteria:

 -  Age < 18 years

 -  Patients with cardiac, pulmonary, neurological, psychiatric or serious metabolic
 conditions not related to CLL / SLL

 -  Altered hepatic function (bilirubin, GOT, GPT, or gammaGT > 2 times upper limit of
 normal) not attributable to CLL / SLL

 -  Altered renal function (creatinine > 1,5 times upper limit of normal)

 -  Patients with serious active infections

 -  Pregnancy and/ or breastfeeding

 -  Patients with positive serology for HBSAG or HBCAB without evaluation by a
 hepatologist

 -  Patients with positive serology for HIV

 -  Life expectancy of less than 12 months

 -  Not taking any other experimental drugs

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to Cladribine (2CdA).