This is a double-blind, randomized, multicenter international Phase 3 study of CAEL-101 combined with standard of care plasma cell dyscrasia (PCD) treatment versus placebo combined with standard of care PCD treatment in Mayo stage IIIa PCD treatment-naïve AL amyloidosis patients. The minimum planned treatment time for each patient will be at least 50 weeks or until the patient’s death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event-driven study, the study will continue, and all patients will continue to receive study treatment until at least 77 deaths have been observed. Approximately 267 patients will be enrolled using a 2:1 randomization ratio. Stratification will be based on geographic region across approximately 70 investigator sites.
Inclusion Criteria
- AL amyloidosis stage IIIb based on the 2013 European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement (Wechalekar 2013, Dispenzieri 2004) (See Table 2) at the time of Screening
- Cardiac involvement as defined by: • Documented clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure
- Planned first-line treatment for plasma cell dyscrasia is CyBorD administered as SoC
Exclusion Criteria
- Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 160 mg dexamethasone (or equivalent corticosteroid) since diagnosis of AL amyloidosis and prior to randomization is allowed.
- Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion
- Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) (Appendix A)
Study Requirements
The patients are followed until the study ends or death, visits are days 1, 8, 15, 22 and then every 2 weeks for the first year, with a follow up visit every 12 weeks in follow up. Research samples are taken fairly frequently. EKGs and Echocardiograms will be performed at various time points throughout the study.
