Daratumumab

Background

Cyclophosphamide, bortezomib and dexamethasone (CyBorD) is standard therapy received by many patients with newly diagnosed systemic AL amyloidosis. Daratumumab is an approved agent for treating multiple myeloma via intravenous infusion. It is not a chemotherapy drug; it belongs to the relatively new class of drugs called targeted therapy. It is an antibody targeting a cell surface protein called CD38, which is found on the abnormal plasma cells that cause myeloma and AL amyloidosis. Daratumumab treatment, in combination with standard chemotherapy, has shown good efficacy in treating myeloma, and preliminary trials in AL amyloidosis have also been encouraging.

Daratumumab is usually given intravenously, which may be challenging for patients with AL amyloidosis whose hearts may be adversely affected by receiving fluids intravenously. In this trial, daratumumab is administered in a novel way by subcutaneous injection, which is hoped to be safer and more effective for patients with AL amyloidosis.

The trial aims to compare outcomes in newly diagnosed patients with AL amyloidosis treated with CyBorD alone to those treated with CyBorD and daratumumab. The study is designed to allow stem cell collection after the first 6 months of therapy so that stem cell transplantation may be considered in the future.

The trial

This is a phase 3 trial to test the primary hypothesis that daratumumab in combination with CyBorD will improve the overall haematological response rate compared to CyBorD alone in patients with AL amyloidosis. Participants are expected to be involved in the trial for around 8 years, which will include a screening phase, treatment phase, post-treatment observation phase and long-term follow up phase.

What the trial involves for patients

The screening phase will involve complete clinical evaluation. In the treatment phase, participants in the experimental group will receive dexamethasone followed by subcutaneous daratumumab, followed by cyclophosphamide and bortezomib on weekly treatment days in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks, then every two weeks for 4 cycles, then every 4 weeks until disease progression or subsequent therapy for a maximum of 2 years. Participants in the active comparator arm will receive the same treatment with CyBorD but without daratumumab. During the treatment phase, adverse events and clinical response will be monitored, during the post treatment observation phase disease evaluations will be performed, and during the long term follow up phase subsequent treatment, treatment response, and clinical status will be followed.

Who can take part in the trial

Patients with newly diagnosed systemic AL amyloidosis. For a full list of exclusion criteria, see the www.clinicaltrials.gov website.

Outcomes

The primary outcome measure is percentage of participants with overall complete haematological response. Secondary outcome measures include progression-free survival, organ response rate, overall survival, change in cancer quality of life questionnaire scores.

Timing

The study is ongoing at UCL.