Phase 1 rolling 6 trial design evaluating safety of a novel BCMA CAR alone (D8 CAR T cells) and of CAR T cells co-expressing BCMA CAR and a CD19 CAR (D8/CAT CAR T cells) in patients with relapsed/ refractory Multiple Myeloma (RRMM). This trial therefore consists of two initial cohorts. Cohort 1 assesses D8 CAR at 50, 150 and 450x10⁶ cells. Cohort 2 assesses a combined D8/CAT CAR at potential doses of 50, 150 and 450x10⁶ cells.

BCMA CAR T cells OR co-expressing BCMA CAR and a CD19 CAR T cells. ATIMP manufacture takes  about 3-4 weeks. During this period, patients may receive bridging therapy to maintain disease control. Prior to ATIMP infusion, patients will receive iv cyclophosphamide 300 mg/m2 and iv fludarabine 30 mg/m2 on days -5 to -3. Patients receive the ATIMP via 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 10 years post ATIMP infusion.

Key Inclusion:

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

1.          Previous diagnosis of systemic light chain amyloidosis
2.        Prior treatment with investigational or approved gene therapy or cell therapy products 
3.       Allogeneic stem cell transplant within 12 months prior to registration into the study and/or moderate /severe chronic GVHD 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 or pulmonary embolism
7.       Patients receiving corticosteroids at a dose of >5 mg prednisolone per day (or equivalent) that cannot be discontinued
8.       Localised radiation to a single site, e.g. for bone pain is permitted at any time
9.       Patients with any anti-myeloma therapy within the last 7 days prior to lymphodepletion or leukapheresis
10.       Inability to tolerate leukapheresis
11.       Life expectancy less than 3 months
12.       Women who are pregnant or breastfeeding
13.       Known allergy to albumin or DMSO