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

Exclusion Criteria29

• 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
• Oxygen saturation ≤ 90% on air
• Patients with clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event
• Left ventricular ejection fraction \< 50% (ECHO or MUGA)
• Corrected QT interval (QTc)\>470 ms on ECG
• 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 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)
• Patients with any major surgical intervention in the last 3 months, cement augmentation for vertebral collapse is permitted
• Patients with active gastrointestinal bleeding
• Patients with active infectious bacterial or viral disease requiring treatment
• 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
• Active autoimmune disease requiring immunosuppression
• Past or current history of other neoplasms
• 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
• Inability to tolerate leucapheresis
• Life expectancy \<3 months
• Women who are pregnant or breastfeeding
• Known allergy to albumin or DMSO
• 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
• 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