Monoclonal Antibodies in Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL) (MARALL)

The treatment of adult B-cell acute lymphoblastic leukaemia (ALL) has progressed considerably in the past 3 decades, particularly due to intensification of chemotherapies, improved supportive care and the incorporation of stem cell transplantation. However, the maximum tolerability of standard chemotherapeutics has been reached in ALL. Using conventional chemotherapy, 80-85% of adults with ALL will achieve a complete remission (CR). Unfortunately treatment at relapse is generally unsuccessful and rarely results, in long-term survival (7% survival at 5 years). Therefore, the investigators are exploring novel treatment strategies through the use of monoclonal antibodies (MoAbs) directed at surface antigens on leukaemic blasts. Using MoAbs directed against surface proteins on B cells has had excellent results in other B-cell diseases such as low and high grade non-Hodgkin lymphomas, without additional toxicity. There has also been limited evidence from small studies and case reports of the efficacy of MoAbs in ALL.

This is a Phase I/II study to determine the safety and tolerability of the combination of veltuzumab and epratuzumab with intensive chemotherapy in patients with relapsed B-cell ALL. A maximum of 51 patients will be treated with a combination of UKALL XII induction chemotherapy and the monoclonal antibodies veltuzumab and epratuzumab. Veltuzumab and epratuzumab are humanised monoclonal antibodies that target CD20 and CD22 surface proteins, respectively. Both of these proteins are expressed on ALL tumour B cells.

One group of patients will receive modified UKALL XII chemotherapy + veltuzumab; a second, modified UKALL XII chemotherapy + epratuzumab and if limited toxicity is found in these first 2 groups, a third group will receive, modified UKALL XII chemotherapy + both veltuzumab and epratuzumab. Patients will be assessed for safety, tolerability and disease response. Safety and tolerability will be measured by the number of Dose Limiting Toxicities (DLTs) in each group. Disease response will be measured by the microscopic appearance of patient bone marrow samples at day 29, and by molecular tests for tumour cells in bone marrow.