Trial Information

A Phase II Trial of Revlimid® as Consolidation Treatment of Residual Disease in Patients With Chronic Lymphocytic Leukemia (CLL)

CLL is the most prevalent leukemia in the western world and is considered incurable.
Standard therapy for CLL is typically in the form of purine analogs, alkylating agents,
monoclonal antibodies, or combinations of these drugs. Unfortunately, despite high
response rates these treatment strategies are considered palliative and all patients
eventually experience disease relapse and with time become less responsive to therapy.
Following standard treatment, CLL patients often fail to achieve a complete response, or
they have minimal residual disease (MRD) in the marrow and this often correlates with a
short time to progression and next therapy.

The National California Institute Working Group and newly updated International Workshop on
Chronic Lymphocytic Leukemia Working Group definition of a complete response (CR) in CLL is
quite permissive and allows for the persistence of 30% of residual lymphocytes in the
marrow. These response criteria were initially developed at a time treatment options for
CLL patients were limited and relatively few CRs were obtained. However, therapeutic
advances including monoclonal antibodies and stem cell transplant have reduced residual CLL
cells to a greater extent than previously possible and necessitated updating of current
response criteria to include MRD evaluation and the development of highly sensitive assays
that can measure MRD such as multiparametric 4-color flow cytometry, allele-specific PCR,
and more convenient investigational assays such as peripheral blood levels of CLLU-1.
Regardless, the majority of complete responses achieved following any initial therapy still
have detectable residual disease.

Importantly, CLL patients who lack minimal residual disease following treatment consistently
demonstrate prolonged progression free survival (PFS) and overall survival (OS) compared
with those with persistent MRD. As such, the development of therapeutic strategies that
have the potential to eradicate disease after therapy are highly desired. Such
consolidation therapies have potential to improve the depth of a remission, prolong PFS, and
potentially overall survival in CLL patients. The investigators propose that Revlimid
might be one such therapy that can be used as consolidation to eradicate residual disease or
improve remissions in patients who have received therapy and that this might lead to a
prolonged disease free duration. The investigators hypothesize that Revlimid will be safe
and well tolerated in this setting.

The investigators further hypothesize that Revlimid consolidation might be effective in CLL
patients at risk of early relapse such as those patients with leukemia cells that use
unmutated immunoglobulin heavy chain variable regions. The investigators found that the
relative CLLU1 expression level on blood samples mirrored the residual level of CLL cells as
determined by 4-color flow cytometry on cells from the aspirated marrow. The investigators
hypothesize that monitoring for expression of CLLU1 might provide a reliable means with
which to evaluate residual disease in the context of Revlimid consolidation therapy.
Previous single agent Revlimid studies have suggested that Revlimid treatment of CLL
patients may positively impact immune parameters increasing the relative composition of
T-lymphocytes, modulation of cytokines, and can lead to improvement immunoglobulin levels
and or the development of leukemia specific antibodies, the investigators hypothesize that
similar changes in immune parameters may occur in the context of Revlimid consolidation
therapy.