NCT01805375

A Phase I Trial of DI-B4 in Patients With Advanced CD19 Positive Indolent B-cell Malignancies

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main aims of this clinical study are to find out the maximum dose that can be given safely to patients, the potential side effects of the drug and how they can be managed. The study will also look at what happens to Anti-CD19 (DI-B4) inside the body. DI-B4 is a type of drug called an Anti-CD19 monoclonal antibody which is being used to stop the growth and kill cancerous immune cells by targeting the B-cell marker (CD-19) expressed on their surface. This drug has not been given to patients before. DI-B4 will be given weekly by intravenous infusion for four weeks. The study is in two parts. In Part 1, small groups of patients will be treated at increasing doses to find the highest safest dose and best dose for part 2 of the study. Approximately 16-20 patients will be treated in this part. In Part 2, the dose identified in Part 1 will be given to approximately 20 patients. Patients recruited to the study will receive four weeks (cycles) of treatment. They will attend an end of therapy visit eight weeks after their last dose of DI-B4, and attend follow-up visits up to eighteen months after their first dose of DI-B4. Information on the overall and progression free survival will be collected for a period up to eighteen months after the final patient is treated on the study. Patients will have blood and urine samples taken each week during treatment amongst other clinical tests. CT scans will be performed at the start of the study, at eight weeks post treatment and six months after the study start. Bone marrow biopsies and FDG-PET scans will only be taken if needed. Research blood samples will also be taken to look at what happens to the drug inside the body. It is important to explain that patients will have advanced cancer so it is unlikely that patients will benefit directly from taking part but the study may help improve future treatment of cancer.

Detailed description

Patients with relapsed or refractory CD19 positive indolent B-cell lymphoma, Waldenström Macroglobulinaemia 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.

Conditions

• Indolent B-cell Lymphoma
• Chronic Lymphocytic Leukaemia
• Waldenström Macroglobulinaemia

Interventions

Type	Name	Description
DRUG	DI-B4	DI-B4 will be administered once weekly for up to a total of four weeks. The starting dose will be 0.02 mg given as an intravenous infusion. A cycle is 1 week in duration and patients should expect to receive a maximum of 4 cycles.

Timeline

• Start date: 2013-04-01
• Primary completion: 2017-12-14
• Completion: 2017-12-14
• First posted: 2013-03-06
• Last updated: 2018-02-05

Locations

5 sites across 1 country: United Kingdom