ALARIC
Research type
Research Study
Full title
BCMA/CD19 targeting CAR T cell for AL Amyloid: Phase 1 trial assessing the treatment of AL Amyloid (relapsed/refractory to previous therapy) with CAR T cells
IRAS ID
1010908
Contact name
Ashutosh Wechalekar
Contact email
Sponsor organisation
University College London
ISRCTN Number
ISRCTN49320109
Research summary
Light chain amyloidosis (AL amyloid) is a subtype of amyloidosis that happens when plasma cells in the bone marrow change. Normally the plasma cells make antibodies. Abnormal plasma cells make extra pieces of antibodies called ‘light chain’ that circulate in the blood and deposit in organs, as amyloid protein fibrils, causing damage.
Treatment of AL amyloidosis includes chemotherapy, proteasome inhibitors, immunomodulatory drugs, antibodies and autologous stem cell transplant.
However, there are patients whose disease returns (relapses) or does not respond to treatment (refractory disease). For these patients, further treatment is needed.
Chimeric Antigen Receptors (CAR) T cells are blood cells genetically engineered to recognise and kill tumour cells. Several CAR T cell therapies have been approved to treat some blood cancers. However currently there are no CAR T cells to treat AL amyloid.
We have developed 2 types of CAR T cells that recognise targets present on the plasma cells. The 1st type targets a protein called BCMA (D8 CAR T cells). The 2nd type targets BCMA and an additional protein, called CD19 present on some plasma cells (D8/CAT CAR T cells) and which has been shown to make the CAR T cells last longer in the body. ALARIC aims to assess whether giving these CAR T cells to participants with relapsed/refractory (r/r) AL amyloid is safe and what dose to use.
We will modify participant’s T cells in a laboratory to make the D8 CAR T cells (targeting BCMA) or D8/CAT CAR T cells (targeting BCMA and CD19). Participants will have 2 chemotherapy drugs to make space for the CAR T cells. The first group of patients will receive D8 CAR T cells; the second group D8/CAT CAR T cells. 2 dose levels will be tested in each group.
The same CAR T cells are tested in patients with r/r multiple myeloma in MCARTY. 15 patients have been treated and results are promising.
We want to test these CAR T cells (at the same dose) in patients with r/r AL amyloid.REC name
London - West London & GTAC Research Ethics Committee
REC reference
25/LO/0139
Date of REC Opinion
2 May 2025
REC opinion
Further Information Favourable Opinion