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

NCT01279707 · Status: UNKNOWN · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 55

Last updated 2014-07-14

No results posted yet for this study

Summary

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.

Conditions

  • Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia

Interventions

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.

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.

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.

Sponsors & Collaborators

  • Gilead Sciences

    collaborator INDUSTRY

  • Queen Mary University of London

    lead OTHER

Principal Investigators

  • Matthew Smith, Doctor · Barts and The London NHS Trust

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
16 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2010-01-31
Primary Completion
2014-08-31
Completion
2014-08-31

Countries

  • United Kingdom

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01279707 on ClinicalTrials.gov