Phase II Study of Tolerance and Efficacy of Subcutanous Low Doses Rituximab Given as Consolidation Treatment to Chronic Lymphocytic Leukaemia (CLL) Patients Responding to Induction Therapy

Chronic Lymphocytic Leukemia (CLL) is still an incurable disease. However recent advances have established correlation between the quality of the response (in particular achievement of negativity of minimal residual disease (MRD) and progression free and overall survival. That is why MRD negative complete remission (CR) is the current goal in CLL treatment.

The association of Rituximab fludarabine cyclophosphamide leads to the best response rate with 52 to 72% CR in "medically" fit untreated CLL patients. MRD results in this setting are still preliminary and around 50%. However many other situations (unfit, elderly, relapse, haematological toxicity leading to early interruption of treatment...) are associated with much lower response rate that would be improved by consolidation treatment.

Monoclonal antibodies are the treatment of choice for consolidation because of sparing marrow and targeting CLL cells. Alemtuzumab has been used for this purpose and results confirm improvement of CR and MRD negative responses but alemtuzumab induced immunodeficiency lead to unacceptable infectious complications. Rituximab monotherapy induces low response rate at standard dose regimen. This is at least partially due to shaving of CD20, mechanism by which CD20 is lost from the leukemic cells but these cells are not cleared. Using low doses of rituximab reduced shaving and allowed CLL cells clearance by the mononuclear phagocytic system. Such low doses of rituximab can be administered subcutaneously.

The investigators then propose subcutaneous low dose rituximab in consolidation to CLL patients responding after induction but having not achieved MRD negative CR.