Doxycycline in AL amyloidosis Phase II RCT. Standard therapy + Doxycycline vs standard therapy Confirmed centres: Christian Medical College, Vellore (Dr. Anup J Devasia) R & R Hospital, Delhi (Dr. Uday Yanamandra) Christian Medical College, Ludhiana (Dr. Chepsy Philip)

RANDOMIZE 4 cycles CyBorD + Doxycycline 100mg BD End points Primary Response after 4 cycles Secondary 3 year EFS 3 year OS Adverse events Organ specific parameters Eligibility Patients with primary systemic amyloidosis Non low risk patients No known hypersensitivity to Doxycycline 4 cycles CyBorD 2 years accrual, 3 years minimum follow up. 80% power to detect 40% improvement in response at 4 months 50 patients in each arm

Investigations at diagnosis After 4 cycles of therapy and Investigations at diagnosis After 4 cycles of therapy and then every 3 months CBC, Creat, Ca, Ph, UA, LFT SPEP, S FLC, IFE 24 hr. U protein, U BJP B2 microglobulin 2DEcho with GLS Trop T, NT Pro BNP BM – asp/trephine/FISH CBC, Creat, Ca, Ph, UA, LFT SPEP, S FLC, IFE 24 hr. U protein, U BJP 2DEcho with GLS Trop T, NT Pro BNP

After 4-6 cycles of therapy Eligible patients will be taken up for autologous SCT. Post ASCT if CR -> Follow up every 3 months If VGPR/PR -> Bortezomib maintenance ± Doxycycline based on the group x 2 years If <PR/PD -> Off the study -> Other regimens. If not eligible/unwilling for transplant. Bortezomib maintenance ± Doxycycline based on the group to which randomized x 2 years. If clinical progression -> off study -> Other regimens.