Trial Information

Combination Antibody Therapy With Apolizumab (1D10) and Rituximab (CD20) in Relapsed Lymphoma and CLL

While recurrent non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are
often responsive to therapy, they are rarely curable and disease control is the primary
therapeutic goal. Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown single
agent activity in these diseases and is currently approved for the therapy of recurrent
indolent lymphoma. However, rituximab induces objective remission in at most 60% of cases
with inevitable relapse. The 1D10 antigen, a subclass of the HLA-DR molecule, is expressed
in a majority of cases of B-cell malignancy. Apolizumab is a humanized monoclonal antibody
that targets this antigen. In a phase I dose escalation trial this antibody has shown
clinical activity against B-cell NHL that express the 1D10 antigen. Acute infusional
toxicity has been tolerable, and a maximum of 5 mg/kg has been given in each of 4 weekly
doses. Preclinical in vitro data from Dr. George Weiner's laboratory suggests at least
additive anti-tumor efficacy when cells are exposed to both antibodies simultaneously. This
trial will pilot the use of combination therapy with rituximab and apolizumab in patients
with tumors that express both antigens. Feasibility and tolerability of the regimen will be
determined. Experimental endpoints will include pharmacokinetics of apolizumab, assessment
of apoptosis in circulating CLL cells by FACS analysis with Annexin 5, assessment of T-and
B-cell dynamics, and effects of rituximab and apolizumab on CLL mRNA as measured by cDNA
microarray. Following the first 21 patients on trial, the administration sequence of
rituximab and apolizumab was changed from rituximab first to apolizumab first to potentially
reduce sensitization of apolizumab toxicity by rituximab.