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

Primary Purpose

Immunoglobulin Light-Chain Amyloidosis

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Thalidomide
Cyclophosphamide
Sponsored by
Guangdong Provincial People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Immunoglobulin Light-Chain Amyloidosis focused on measuring AL Amyloidosis, Bortezomib, cyclophosphamide, thalidomide, randomized controlled trial, prognosis, Side effect

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Guangdong Provincial People'S HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group1

Group2

Arm Description

Group1 is the AL amyloidosis patients who have bortezomib-thalidomide-dexamethason-based regimens for their treatment.

Group2 is the AL amyloidosis patients who have bortezomib-cyclophosphamide-dexamethason-based regimens for their treatment.

Outcomes

Primary Outcome Measures

Hematologic Response
According to the criteria of hematologic response of AL amyloidosis.

Secondary Outcome Measures

Organ Response
According to the criteria of organ response of AL amyloidosis.

Full Information

First Posted
June 15, 2020
Last Updated
October 27, 2020
Sponsor
Guangdong Provincial People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04612582
Brief Title
Comparison of BTD and BCD Based Regimens in the Treatment of AL Amyloidosis
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 1, 2020 (Actual)
Primary Completion Date
January 31, 2023 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guangdong Provincial People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immunoglobulin Light-Chain Amyloidosis
Keywords
AL Amyloidosis, Bortezomib, cyclophosphamide, thalidomide, randomized controlled trial, prognosis, Side effect

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Patients who meet the entry criteria will randomly enter the BTD or BCD treatment group according to the proportion of 1:1. The random code will be generated by computer and the random envelope will be made according to the random code. Treatment group included. Each code has a corresponding random envelope. According to the time sequence of subjects meeting the entry criteria, the random number of subjects will be given from small to large. The corresponding random envelope can only be opened during grouping. If a random number falls off in the middle of use, it can no longer be used.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group1
Arm Type
Experimental
Arm Description
Group1 is the AL amyloidosis patients who have bortezomib-thalidomide-dexamethason-based regimens for their treatment.
Arm Title
Group2
Arm Type
Experimental
Arm Description
Group2 is the AL amyloidosis patients who have bortezomib-cyclophosphamide-dexamethason-based regimens for their treatment.
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Other Intervention Name(s)
Bortezomib, Dexamethason
Intervention Description
Bortezomib (d 1, 8, 15, 22, 1.3mg /m2, subcutaneous injection); thalidomide (d 1-28 50-100mg, oral); dexamethason (d 1, 2, 8, 9, 15, 16, 22, 23, 20mg, oral/intravenous injection) as a course of treatment, the patients will complete six courses of treatment after entering the group, and the total observation time is one year after the end of treatment.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Bortezomib, Dexamethason
Intervention Description
Bortezomib (d 1, 8, 15, 22,1.3mg / m2, subcutaneous injection); cyclophosphamide (d 1, 2,900mg / m2, intravenous drip); dexamethason (d 1, 2, 8, 9,15, 16, 22, 23, 20mg, oral/intravenous injection) as a course of treatment, patients will complete six courses of treatment after entering the group, the overall observation time is one year after the end of treatment.
Primary Outcome Measure Information:
Title
Hematologic Response
Description
According to the criteria of hematologic response of AL amyloidosis.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Organ Response
Description
According to the criteria of organ response of AL amyloidosis.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Pathological biopsy showed non-AL amyloidosis; Abnormal proliferation of plasma cells reached the standard of multiple myeloma; Other hematological system tumors; Cushing's syndrome; Active hepatitis; 5.Pregnant or lactating women;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenjian Wang, PhD
Phone
0086-020-83827812-61421
Email
wwjph@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenjian Wang, PhD
Organizational Affiliation
Guangdong Provincial People's Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Guangdong Provincial People'S Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenjian Wang, PhD
Phone
0086-020-83827812-61421
Email
wwjph@126.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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27536686
Citation
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Comparison of BTD and BCD Based Regimens in the Treatment of AL Amyloidosis

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