Phase1 rolling 6 trial design evaluating safety of a novel BCMA CAR alone (D8 CAR Tcells) and of CAR T cells co-expressing BCMA CAR and a CD19 CAR (D8/CAT CAR Tcells) in patients with relapsed/ refractory Multiple Myeloma (RRMM). Thistrial therefore consists of two initial cohorts. Cohort 1 assesses D8 CAR at 50and 150x10⁶ cells. Cohort 2 assesses a combined D8/CAT CAR and has 2potential doses of 50 and 150x10⁶ cells

BCMA CAR Tcells OR co-expressing BCMA CAR and a CD19 CAR T cells.ATIMP manufacture takes about 15 days. During thisperiod, patients may receive bridging therapy to maintain disease control.Prior to ATIMP infusion patients will receive iv cyclophosphamide 60mg/kg andiv fludarabine 30 mg/m2 on Days -5 to -3. Patients receive the ATIMP via asingle intravenous infusion.Patients will be followed up regularly(with daily, weekly and monthly visits) until 2 years post ATIMP infusion. After 2 years patients will continue to be followed up annually until 10years post ATIMP infusion.

Key Inclusion:

1. Age ≥ 18
2. Relapsed/Refractory Multiple Myeloma
3. Secretory disease: PP≥5g/L and/or sFLC≥100mg/L of involved light chain with abnormal K:L ratio.
4. ≥3 prior lines of therapies (including PI (proteasome inhibitor), IMiD (immunomodulatory drugs), antiCD38 antibody

1.          Previous diagnosis of systemic light chainamyloidosis
2.        Prior treatment with investigational orapproved gene therapy or cell therapy products 
3.       Allogeneic stem cell transplant within 12months prior to registration into the study and/or moderate /severe chronicGVHD requiring immunosuppressive therapy and/or systemic steroids
4.       Active infectious bacterial or viral disease 
5.       Known CNS involvement
6.       Medical history including: other neoplasms,autoimmune disease, chronic renal impairment, significant liver disease, DVT orpulmonary embolism
7.       Patients receiving corticosteroids at a doseof >5 mg prednisolone per day (or equivalent) that cannot be discontinued
8.       Use of rituximab (or rituximab biosimilar)within the last 3 months prior to CAR T cell infusion or leukapheresis. 
9.       Localised radiation to asingle site, e.g. for bone pain is permitted at any time
10.       Patients with any anti-myeloma therapy withinthe last 7 days prior to LD or leukapheresis
11.       Inability to tolerate leukapheresis
12.       Life expectancy
13.       Women who are pregnant or breastfeeding
14.       Known allergy to albumin or DMSO