Amyloidosis; Systemic
Conditions
Keywords
Primary light chain amyloidosis, Doxycycline, Bortezomib, Prognosis, Progression-free survival, Overall survival, Organ response
Brief summary
Survival of intermediate and high-risk primary light chain amyloidosis (pAL) remains poor due to high mortality within 3-6 months of diagnosis. Rapidly effective regimens such as bortezomib, cyclophosphamide and dexamethasone (BCD) still failed to overcome the poor prognosis in very advanced pAL amyloidosis patients. Recently, doxycycline was demonstrated to induce disruption of fibril formation and reduce the number of intact fibrils in transgenic mouse model of pAL amyloidosis. Furthermore, case-control study suggested that adjuvant oral doxycycline could improve response and survival in cardiac pAL amyloidosis, which necessities further confirmation through a randomized trial. Therefore, we designed a multi-center randomized open-label controlled study to investigate the efficacy and safety of co-administration of oral doxycycline with BCD regimen in treatment-naïve patients with Mayo stage II-III pAL amyloidosis. The primary outcome progression-free survival, and secondary endpoints including overall survival, hematologic response, organ response and toxicity of doxycycline will be evaluated.
Interventions
DRUGDoxycycline
Oral doxycycline 100mg twice daily
DRUGBortezomib
1.3mg/m2 of bortezomib on days 1, 8, 15 and 22 of a 35-day cycle
DRUGCyclophosphamide
300mg/m2 cyclophosphamide on days 1, 8, 15 and 22 of a 35-day cycle
DRUGDexamethasone
40mg of dexamethasone on days 1, 8, 15 and 22 of a 35-day cycle
Sponsors
Peking University First Hospital
Beijing Anzhen Hospital
Beijing Chao Yang Hospital
West China Hospital
Tongji Hospital
Union Hospital Affiliated with Tongji Medical College of HUST
Shanghai Changzheng Hospital
Nanfang Hospital, Southern Medical University
Jian Li
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years old adults. * Biopsy proved treatment-naïve pAL amyloidosis. * Mayo 2004 stage II-III. * dFLC \> 50mg/L. * Patient must provide informed consent.
Exclusion criteria
* Co-morbidity of uncontrolled infection. * Co-morbidity of grade 2 or 3 atrioventricular block. * Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia. * Co-morbidity of other active malignancy. * Co-diagnosis of multiple myeloma or waldenstrom macroglobulinemia. * Grade 2 or higher neuropathy according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. * Allergic history of doxycycline. * Neutrophil \<1×10E9/L，hemoglobin \< 7g/dL，or platelet \< 75×10E9/L. * Severely compromised hepatic or renal function: ALT or AST \> 2.5 × ULN, total bilirubin \> 1.5mg/dL，or eGFR \< 60mL/min.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | 2 years | The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 2 years | The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure. |
| Hematologic response | 2 years | The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure. |
| Organ response | 2 years | The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure. |
| Adverse events | up to 2 years | Adverse events are collected until 30 days after last dose of doxycycline. |
Countries
China
Outcome results
None listed