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.

Eligibility Criteria:
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).