Comparison of BTD and BCD Based Regimens in the Treatment of AL Amyloidosis

A Comparative Study of Bortezomib-Thalidomide-Dexamethason and Bortezomib-Cyclophosphamide-Dexamethason in the Treatment of Monoclonal Immunoglobulin Light Chain Amyloidosis: A Prospective Randomized Controlled Trial（BTD-CHINA-TRIAL）

Research Objective:At present, there is no standard therapeutic regimen for monoclonal immunoglobulin light chain (AL) amyloidosis in the world. To compare the efficacy and safety of the regimens between bortezomib-thalidomide-dexamethasone (BTD) and bortezomib-cyclophosphamide-dexamethasone (BCD) in the treatment of AL amyloidosis, so as to provide more clinical evidence for the standard treatment for the disease.

Research Design:This study was designed as a prospective, randomized and controlled clinical study. Patients who meet the inclusion criteria of this study will be randomized to the BTD scheme group or BCD scheme group.

Object and source:Patients meeting the inclusion criteria of AL amyloidosis are enrolled into the study. Screening failure rate ≤ 30%, follow-up dropout rate ≤ 10%.

Sample size evaluation: The complete remission rate (CR) and the very good partial remission rate (VGPR) were used as statistical indexes for hematology remission rate estimation. Referring to the previous literature, the CR and VGPR of bortezomib-thalidomide-dexamethasone (BTD) is 83%, and CR and VGPR of bortezomib-cyclophosphamide-dexamethasone (BCD) is 43%. The boundary value is 0.1, according to the level of significance level α = 0.05, test efficacy 1 - β = 0.8, using the method of effectiveness test, using pass11 software calculation to estimate the sample size to be included in the group, the expected dropout rate is 20%, the total sample size is 70, 35 in each group.

Observation index:Before and after treatment, physical examination should be carried out every month. The following test should be required. Blood pressure

, blood routine, liver function, electrolyte, 24h urine volume, 24h urine protein quantity, urine protein/creatinine ratio, blood uric acid, serum albumin, urea nitrogen, creatinine, eGFR(estimated Glomerular Filtration Rate), blood lipids, infection index, NT-proBNP (N terminal pro B type natriuretic peptide), TNT(Troponin-T), blood and urine free light chain should be detected respectively.

Quality assurance plan:The study shall be conducted in accordance with the current approved protocol and the July 1996 ICH drug clinical study management code (CPMP/ICH / 135/95) (ICH GCP), the Helsinki declaration, regulations and standard operating procedures.

Plan for missing data:(1)When the subject falls off, the researcher should contact the subject as soon as possible by means of visiting, making an appointment for follow-up, making phone calls, sending letters, etc., asking the reason, making record as much detail as possible.(2)All patients with abscission should be recorded for ITT analysis. There is no need for replacement for exfoliated patients. (3)If a patient withdraws from the study due to anaphylaxis, adverse reactions or ineffective treatment, the investigator shall take corresponding treatment measures according to the actual situation of the subject.

Statistical analysis plan:The main evaluation indexes were hematology CR and VGPR, organ function CR and VGPR. The statistical index of treatment effect is the number of patients who meet the criteria of CR and VGPR. Conclusion: if P > 0.05, H0 hypothesis cannot be rejected according to the test level of single side α = 0.05, that is to say, it cannot be judged that the treatment of light amyloidosis in BTD group is better than that in BCD group; if P ≤ 0.05, it can be considered that the treatment of light amyloidosis in BTD group is better than that in BCD group. The difference between the two groups was analyzed by chi square test or Fisher exact probability test as a secondary evaluation index (the overall survival rate and progression free survival period were observed after one year follow-up after six courses of treatment).The safety analysis set includes all cases entering the study and using at least one dose of the study drug. Chi square test or Fisher exact probability test were used to analyze the incidence of adverse events in the two groups. Chi square test or McNemar test were used to analyze the change of abnormal rate of laboratory indexes from baseline.

Inclusion Criteria:

1.Signed the written informed consent; 2.18 years old ≤ age ≤ 80 years old, no restriction on gender; 3.AL amyloidosis was confirmed by pathological biopsy in the accumulated system or organ (kidney, heart, liver, skin), and excluded other secondary factors; 4.The proliferation of monoclonal plasma cells was confirmed by fixed electrophoresis of bone marrow or blood/urine.

Exclusion Criteria:

1. Pathological biopsy showed non-AL amyloidosis;
2. Abnormal proliferation of plasma cells reached the standard of multiple myeloma；
3. Other hematological system tumors;
4. Cushing's syndrome;
5. Active hepatitis;

5.Pregnant or lactating women;