Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia

Abstract

Preclinical data demonstrate enhanced antitumor effect when lumiliximab, an anti-CD23 monoclonal antibody, is combined with fludarabine or rituximab. Clinical data from a phase 1 trial with lumiliximab demonstrated an acceptable toxicity profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). We therefore pursued a phase 1/2 dose-escalation study of lumiliximab added to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated CLL patients. Thirty-one patients received either 375 mg/m 2 (n ‫؍‬ 3) or 500 mg/m 2 (n ‫؍‬ 28) of lumiliximab in combination with FCR for 6 cycles. The toxicity profile was similar to that previously reported for FCR in treatment of relapsed CLL. The overall response rate was 65%, with 52% of patients achieving a complete response (CR), which compares favorably with the CR rate previously reported for the FCR regimen alone in relapsed CLL. The estimated median progression-free survival for all responders was 28.7 months. The addition of lumiliximab to FCR therapy is feasible, achieves a high CR rate, and does not appear to enhance toxicity in previously treated patients with CLL. A randomized trial comparing lumiliximab plus FCR with FCR alone is underway to define the benefit of this combination in relapsed CLL. This trial was registered at clinicaltrials.gov as NCT00103558. (Blood. 2010;115:489-495)

Refractory chronic lymphocytic leukemia - new therapeutic strategies

“…Compared to a historic cohort treated with FCR [12], the CR rate was twice as high (52 % vs. 25 %). The toxicity was comparable [21].…”

Changes in Antigen Expression in a Follow-up of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

“…The humanized anti-CD23 has been developed and used in clinical trials [16]. A phase I/II clinical trial showed that the addition of anti-CD23 to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated CLL/SLL patients resulted in a higher complete response rate, and did not appear to enhance toxicity, indicating that anti-CD23 synergistically enhances antitumor activity of FCR [17]. The investigation of the relation between the levels of CD23 expression and clinical response may be beneficial to achieve the best therapeutic effect without inadvertent addition of toxicity.…”

Monoclonal Antibodies in Chronic Lymphocytic Leukemia

“…[65][66][67][68] This is also the case for CD19, a glycoprotein member of the Ig superfamily, 69 and HLA-DR, a class II antigen of the major histocompatibility complex. 70 In a Phase I/II study, 91 patients with relapsed/ refractory NHL, CLL, and multiple myeloma were enrolled to receive MEDI-551, an antibody targeting CD19.…”