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
1. Histologically proven relapsed or refractory indolent B-cell lymphoma or chronic
lymphocytic leukaemia. Patients must have received at least one line of previous therapy.
2. CD19 positive malignancy as demonstrated by immunohistochemistry or flow cytometry
3. Life expectancy of at least 12 weeks
4. World Health Organisation (WHO) performance status of 0-1 (Appendix 1)
5. Haematological and biochemical indices within the ranges shown below. These
measurements must be performed within one week (Day -7 to Day 1) before the patient
commences treatment with DI-B4.
Laboratory Test Value required Haemoglobin (Hb)
≥ 9.0 g/dL (red cell support is permissible), Absolute neutrophil count (ANC) ≥1.0 x
10^9/L (or ≥0.5 x 10^9/L if bone marrow involvement), Platelet count
≥75 x 10^9/L (or ≥50 x 10^9/L if bone marrow involvement), Serum bilirubin
≤1.5 x upper limit of normal (ULN) Alanine amino-transferase (ALT) and/or aspartate
amino-transferase (AST) ≤ 2.5 x (ULN) unless raised due to
hepatic involvement in which case up to 5 x ULN is permissible Calculated creatinine
clearance (Cockroft-Gault formula) ≥30 ml/min (uncorrected value)
6. 18 years or over
7. Written (signed and dated) informed consent and be capable of co-operating with
treatment and follow-up
1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy,
chemotherapy or investigational medicinal products during the previous 4 weeks before
2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or
certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug
Development Office (DDO) should not exclude the patient.
3. Known to be serologically positive for hepatitis B (unless due to vaccination),
hepatitis C or human immunodeficiency virus (HIV).
4. Patients with clinically active leptomeningeal or central nervous system
5. Patients with transformed lymphoma from a pre-existing indolent lymphoma. Patients with
a previous history of transformation, but on this disease episode have a biopsy proven
indolent recurrence may be included.
6. Patients receiving corticosteroids, except where the patient has been on a stable dose
for the preceding seven days. Doses of prednisolone or equivalent >10 mg daily are not
permitted whilst on the study.
7. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease
(New York Heart Association [NYHA] - refer to Appendix 5), prior history of cardiac
ischaemia or prior history of cardiac arrhythmia.
8. Ability to become pregnant (or already pregnant or lactating). However, those female
patients who have a negative serum or urine pregnancy test before enrolment and agree to
use two highly effective forms of contraception (oral, injected or implanted hormonal
contraception and condom, have an intra-uterine device and condom, diaphragm with
spermicidal gel and condom) during the trial and for six months afterwards are considered
9. Male patients with partners of child-bearing potential (unless they agree to take
measures not to father children by using one form of highly effective contraception
[condom plus spermicide] during the trial and for six months afterwards). Men with
pregnant or lactating partners should be advised to use barrier method contraception (e.g.
condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
10. Major thoracic or abdominal surgery from which the patient has not yet recovered.
11. At high medical risk because of non-malignant systemic disease including active
12. Is a participant or plans to participate in another interventional clinical trial,
whilst taking part in this Phase I study of DI-B4. Participation in an observational trial
would be acceptable.
13. Any other condition which in the Investigator‟s opinion would not make the patient a
good candidate for the clinical trial.