Monoclonal antibodies in recurrent B cell ALL (MARALL)

• Research type

  Research Study

• Full title

  Phase I/II study combining humanised anti-CD20 (veltuzumab), anti-CD22 (epratuzumab) and both monoclonal antibodies with intensive chemotherapy in adults with recurrent B-precursor acute lymphoblastic leukaemia (ALL) - MARALL

• IRAS ID

  13327

• Contact name

  Matthew White

• Sponsor organisation

  R & D Office, Queen Mary University London

• Eudract number

  2008-002286-32

• ISRCTN Number

  ISRCTN

• Clinicaltrials.gov Identifier

  NCT

• Research summary

  The treatment of adult B-cell acute lymphoblastic leukaemia (ALL) has progressed considerably in the past 3 decades due to intensification of chemotherapies, improved supportive care and stem cell transplantation. However, the maximum tolerability of standard chemotherapeutics has been reached in ALL. Using conventional chemotherapy, 80-85% of adults with ALL achieve a complete remission (CR). Unfortunately treatment at relapse is generally unsuccessful and rarely results in long-term survival (7% survival at 5 years). We 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 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 epratzumab with intensive chemotherapy in patients with relapsed B-cell ALL. A maximum of 55 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 UKALL XII veltuzumab; a second, UKALL XII epratuzumab and if acceptable toxicity is found in these first 2 groups, a third group will receive, UKALL XII 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 tumor cells in bone marrow (an optional Minimal Residual Disease feasibility study).

• REC name

  London - Harrow Research Ethics Committee

• REC reference

  09/H0709/42

• Date of REC Opinion

  10 Aug 2009

• REC opinion

  Further Information Favourable Opinion