Tolerance and Efficacy of Subcutanous Low Doses Rituximab for CLL Consolidation Treatment
Status:
Unknown status
Trial end date:
2015-06-01
Target enrollment:
Participant gender:
Summary
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.