Belimumab in Patients With Chronic Lymphocytic Leukemia
Status:
Not yet recruiting
Trial end date:
2027-07-14
Target enrollment:
Participant gender:
Summary
This study is a phase II trial of belimumab in combination with rituximab/venetoclax in
patients with refractory or relapsed chronic lymphocytic leukemia (CLL). Treatment of CLL has
drastically changed in the past years as new therapeutic agents have gained clinical
approval. The combination rituximab/venetoclax over a course of two years is approved as
second line therapy especially in patients with high risk CLL (del17p), showing high
remission rates and achievement of MRD (minimal residual disease) negativity. The next goals
in CLL therapy are now to increase the rate of MRD negativity and to achieve an earlier MRD
negativity during the course of treatment to allow for a reduction of treatment time and
therefore treatment-induced toxicities. In line with other hematologic diseases, progression
free survival depends on remission status, especially MRD negativity, after last treatment as
MRD positivity after therapy indicates the persistence of treatment resistant CLL cells. One
mechanism of therapy resistance has been described as reduced sensitivity to
rituximab-induced antibody dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK)
cell production of B-lymphocyte stimulator (BlyS, also called BAFF), which can be bound by
belimumab, a human anti-BAFF antibody. Moreover, recombinant human (rh)BAFF can dose
dependently reverse cytotoxic effects of venetoclax, which could also be restored by the
application of belimumab. This led to the conceptualization of this clinical trial, in which
belimumab is applied as a weekly subcutaneous injection in combination with
standardrituximab/venetoclax treatment for up to 24 months in relapsed and refractory CLL
patients. By removing BAFF from the CLL microenvironment we aim to increase the efficacy of
rituximab/venetoclax treatment to achieve higher and earlier MRD negativity rates and allow
for an abbreviated treatment.