A Cancer Research UK Phase I Trial of the Anti-CD19 DI-B4 Monoclonal Antibody Given Intravenously, Weekly for Four Weeks, in Patients With Advanced CD19 Positive Indolent B-cell Malignancies
Patients with relapsed or refractory CD19 positive indolent B-cell lymphoma or chronic
lymphocytic leukaemia will be entered into this study.
For the vast majority of patients, B-cell non Hodgkin lymphoma and chronic lymphocytic
leukaemia are incurable using existing therapeutic approaches.
Although anti-CD20 directed therapy has improved outcomes, more than fifty percent of
patients still relapse following treatment or are refractory to it and therefore additional
novel non-cross resistant therapies are urgently required.
DI-B4 is a humanised, low-fucosylated anti-CD19 Immunoglobulin (Ig) G1 monoclonal antibody
with potent antibody-dependent cell-mediated cytotoxicity (ADCC) but minimal complement
dependent cytotoxicity (CDC). The target antigen, CD19, is the canonical B-cell marker that
is expressed on all B-cells including the malignant B-cells in NHL, CLL and acute
lymphoblastic leukaemia (ALL). The CD19 antigen is therefore an attractive B-cell lineage
specific target for monoclonal antibody therapy. DI-B4 is expected to act through the
depletion of normal and malignant CD19 positive cells, primarily via ADCC.
This is a multi-centre, Phase I, dose escalation/dose expansion study. For the first three
cohorts, an intra-patient dose escalation scheme will be followed unless a DLT is observed.
From Cohort 4 onwards, a standard 3 + 3 dose escalation schedule of DI-B4 will be continued
until the maximum tolerated dose (MTD) is defined, up to a maximum dose of 1000mg.
Interventional
Primary Purpose: Treatment
To recommend a dose for future trials with a new drug called DI-B4 by finding the highest safe dose which can be given to patients
38 Months
Yes
United Kingdom: Medicines and Healthcare Products Regulatory Agency
CRUKD/12/003
NCT01805375
April 2013
Name | Location |
---|