Monoclonal Antibodies in Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL) (MARALL) (MARALL)
Recruitment status was: Active, not recruiting
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.
|Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia||Biological: humanised monoclonal antibody, veltuzumab Biological: humanised monoclonal antibody epratuzumab Biological: humanised monoclonal antibodies veltuzumab and epratuzumab||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study Combining Humanised Anti-CD20 (Veltuzumab), Anti-CD22 (Epratuzumab) and Both Monoclonal Antibodies With Intensive Chemotherapy in Adults With Recurrent or Refractory B-precursor Acute Lymphoblastic Leukaemia (ALL)|
- The total number of dose limiting toxicity events (DLTs) to measure safety and tolerability [ Time Frame: Day 29 ]The primary objective is to assess the safety and tolerability of the combination of veltuzumab and/or epratuzumab with intensive chemotherapy for recurrent or refractory adult B-precursor ALL.
- Morphological and molecular remission in bone marrow [ Time Frame: Day 29 ]
Achievement of morphological complete remission on Day 29 bone marrow
Efficacy of treatment to achieve MRD negativity, and investigate a possible association between the intensity of CD20 and CD22 antigen expression and treatment activity.
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: A: Veltuzumab and chemotherapy
Veltuzumab and modified UKALL XII chemotherapy
Biological: humanised monoclonal antibody, veltuzumab
Veltuzumab with modified UKALL XII induction chemotherapy. Veltuzumab will be administered at 200 mg/m2 IV on Day 8 and subsequently, (if tolerated on Day 8), over 1 hour on Days 15, 22, 29.
Experimental: B: epratuzumab and chemotherapy
epratuzumab and modified UKALL XII chemotherapy
Biological: humanised monoclonal antibody epratuzumab
Epratuzumab with modified UKALL XII induction chemotherapy. Epratuzumab will be administered at 360 mg/m2 IV over 1 hour on Days 8, 15, 22 and 29.
Experimental: C: veltuzumab and epratuzumab and chemotherapy
Veltuzumab and Epratuzumab and modified UKALL XII chemotherapy
Biological: humanised monoclonal antibodies veltuzumab and epratuzumab
Epratuzumab + Veltuzumab with modified UKALL XII induction chemotherapy. Epratuzumab will be administered at 360 mg/m2 IV over 1 hour on Days 8, 15, 22 and 29. Veltuzumab will be administered at 200 mg/m2 IV over 2 hours on Day 8 and over 1 hour on Days 15, 22 and 29. Veltuzumab will be infused 1 hour after the infusion of epratuzumab.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01279707
|University Hospitals Birmingham NHS Foundation|
|Birmingham, United Kingdom, B15 2TH|
|University of Bristol Foundation Trust|
|Bristol, United Kingdom, BS2 8BJ|
|University Hospital of Wales|
|Cardiff, United Kingdom, CF14 4XN|
|Beatson West of Scotland Cancer Centre|
|Glasgow, United Kingdom, G12 0YN|
|Leeds Teaching Hospitals NHS Trust|
|Leeds, United Kingdom, LS9 7TF|
|Barts and the London NHS Trust|
|London, United Kingdom, EC1A 7BE|
|Royal Free Hampstead NHS Trust|
|London, United Kingdom, NW3 2QG|
|Newcastle, United Kingdom, NE2 4HH|
|Nottingham City Hospital|
|Nottingham, United Kingdom, NG5 1PB|
|Plymouth Hospitals NHS Trust|
|Plymouth, United Kingdom, PL6 8DH|
|Principal Investigator:||Matthew Smith, Doctor||Barts and The London NHS Trust|