A New Study Evaluating the Activity of Modular CAR T for mYeloma

Prior treatment

• Previous diagnosis of systemic light chain amyloidosis
• Prior treatment with investigational or approved gene therapy or cell therapy products
• Stem cell transplant patients only:
  • allogeneic stem cell transplant within 12 months prior to registration into the study
  • moderate/ severe chronic GVHD (NIH consensus criteria) requiring immunosuppressive therapy and/or systemic steroids
• Patients with any major surgical intervention in the last 3 months, cement augmentation for vertebral collapse is permitted
• Known active central nervous system involvement of MM. History or presence of clinically relevant central nervous system pathology such as epilepsy, paresis, aphasia, stroke within 3 months prior to enrolment, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis
• Patients receiving corticosteroids at a dose of \>5 mg prednisolone per day (or equivalent) that cannot be discontinued
• Received any radiotherapy within the last 7 days prior to lymphodepletion or leukapheresis. Localised radiation to a single site, e.g. for bone pain is permitted at any time
• Patients with any anti-myeloma therapy within the last 7 days prior to LD or leukapheresis

Other illness

• Patients with clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event
• Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded)
• History or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at preconditioning
• Chronic renal impairment requiring dialysis
• Patients with active gastrointestinal bleeding
• Patients with active infectious bacterial or viral disease requiring treatment
• Active autoimmune disease requiring immunosuppression
• Past or current history of other neoplasms
• Active infection requiring systemic anti-microbial therapy, or with temperature more or equal to 38 C within 48 hours before scheduled CAR-T cell infusion

Lab values

• Left ventricular ejection fraction \< 50% (ECHO or MUGA)
• Corrected QT interval (QTc)\>470 ms on ECG
• Patients with significant liver disease: alanine aminotransferase or aspartate aminotransferase ≥3x upper limit normal (ULN), or total bilirubin ≥25umol/L (1.5mg/dL), except in patients with Gilbert's syndrome, or evidence of end-stage liver disease (e.g. ascites, hepatic encephalopathy)
• Known allergy to albumin or DMSO

Other

• Oxygen saturation ≤ 90% on air
• Inability to tolerate leucapheresis
• Life expectancy \<3 months
• Women who are pregnant or breastfeeding
• Requirement for supplementary oxygen at the time of scheduled CAR-T cell infusion
• Clinical deterioration of organ functions (hepatic or renal function) exceeding criteria set at study entry

• Age ≥ 18
• Relapsed/Refractory Multiple Myeloma
• Secretory disease: PP≥5g/L and/or sFLC≥100mg/L of involved light chain with abnormal K:L ratio.
• ≥3 prior lines of therapies (including proteasome inhibitor, IMiD, anti CD38 antibody)
• Refractory to last line of therapy (not achieved at least PR and progressed within 60 days of last dose or achieved at least PR but progressed within 6 months of last dose)
• Has previously received or is not suitable for ASCT
• Eastern Cooperative Oncology Group (ECOG) performance status 0/1
• Creatinine Clearance (CrCl)≥40ml/min, Absolute Neutrophil Count (ANC)≥1x10\^9/L, Platelets (plt)≥50x10\^9/L, Haemoglobin (Hb)≥80 /L, lymphocyte count ≥0.3x10\^9/L
• Patients must weigh \>30 kg
• Agreement to have a pregnancy test, use adequate contraception (if applicable)
• Written informed consent