Combination of Daratumumab and BD Regimen and Dapagliflozin in the Treatment of M-protein Related Cardiac Disease

NCT06297681 | Not Yet Recruiting

• 1 other identifier: 2023-1-27-2
• Study Type: observational
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

It is expected to include 40 patients with M-protein related cardiac disease. The treatment medication for enrolled patients must comply with the treatment regimen of Daratumumab + Bortezomib + Dexamethasone. All patients were given Dapagliflozin 10mg/day at the beginning of treatment (creatinine clearance rate greater than 20ml/min).

Conditions

M-protein Related Cardiac Disease

Keywords

M-protein related cardiac disease; daratumumab; dapagliflozin; bortezomib; dexamethasone

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The percentage of cases that achieved complete response (CR) and partial response (PR) after treatment compared to the total evaluable cases.

  After 6 cycles of treatment (28 days as 1 cycle)

Secondary Outcomes (4)

• 2-year PFS rate, progression free survival (PFS)

  Treatment for 2 years

• 2-year OS rate, overall survival (OS)

  Treatment for 2 years

• Duration of Relief (DOR)

  Treatment for 2 years

• Next treatment time (TTNT)

  Treatment for 2 years

Study Arms (1)

newly diagnosed M-protein related cardiac disease group

M-protein related cardiac disease aged 18 and above (at least one of the following criteria is met): (1) Systemic amyloidosis of the affected heart; (2) Presence of M component and presence of arrhythmia, cardiac enzyme abnormalities, cardiac function abnormalities, and exclusion of other diagnosable cardiac diseases. It is expected to include 40 patients with M-protein related cardiac disease. The treatment medication for enrolled patients must comply with the treatment regimen of Daratumumab + Bortezomib + Dexamethasone. All patients were given Dapagliflozin 10mg/day at the beginning of treatment (creatinine clearance rate greater than 20ml/min).

Drug: Daratumumab + Bortezomib + Dexamethasone + Dapagliflozin

Interventions

Daratumumab + Bortezomib + Dexamethasone + Dapagliflozin DRUG

The treatment medication for enrolled patients must comply with the treatment regimen of Daratumumab + Bortezomib + Dexamethasone: subcutaneous injection of 1800mg of Daratumumab, d1, 8,15,22 (28 day cycle); (After 2 cycles of improvement in cardiac indicators, it can be adjusted to intravenous injection of daratumumab); Bortezomib 1.3 mg/m2 d1, 8, 15, 22; D1, 8, 15, 22; Dexamethasone 20 mg d1, 2, 8, 9, 15, 16, 22, 23. When NTProBNP is greater than 5400ng/ml, bortezomib 1.0mg/m2; When NTProBNP is greater than 8500ng/ml, bortezomib is 0.7mg/m2. When NTProBNP is greater than 10000ng/ml, bortezomib is temporarily not allowed; NTProBNP greater than 4500ng/ml dexamethasone starts at 10 mg/dose. All patients were given Dapagliflozin 10mg/day at the beginning of treatment (creatinine clearance rate greater than 20ml/min).

newly diagnosed M-protein related cardiac disease group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Observe patient data from Beijing Chaoyang Hospital affiliated with Capital Medical University, Beijing Chuiyangliu Hospital, and Beijing Boren Hospital.

You may qualify if:

• ECOG score 0-2;
• Sign a written informed consent form.

You may not qualify if:

• Acute myocardial infarction;
• Severe functional abnormalities in important organs such as lungs, liver, and kidneys (the carbon monoxide diffusion ability caused by chronic respiratory diseases is 50% lower than expected);
• Major surgery, radiation therapy, infections requiring systemic antibiotic treatment, or other serious infections within 14 days after enrollment;
• Individuals with mental illness, comprehension disorders, or other reasons that make it difficult to control themselves;
• Pregnant or lactating women, as well as reproductive age patients who refuse to take appropriate contraceptive measures during this trial. If the patient is male, refuse to use adequate contraceptive methods or donate semen during the study period and within 3 months after receiving the last cycle of drug study;
• Diagnosed or treated another malignant tumor within 2 years prior to enrollment;
• Individuals with allergies to daratumumab, bortezomib, or dexamethasone components or more severe allergic constitutions;
• HIV infected individuals (HIV antibody positive);
• Active infection of hepatitis B and hepatitis C (hepatitis B B virus surface antigen positive and/or hepatitis B core antibody positive, hepatitis B virus DNA more than 1x103 copies/mL; hepatitis C virus RNA more than 1x103 copies/mL);
• Participate in another clinical trial 30 days after the start of the trial and throughout the entire trial period;
• The researcher determined that patients who are not suitable to participate in this study;

Sponsors & Collaborators

• Beijing Chao Yang Hospital: lead
• Beijing Chuiyangliu Hospital: collaborator
• Beijing Boren Hospital: collaborator

Related Publications (5)

• Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schonland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021 Jul 1;385(1):46-58. doi: 10.1056/NEJMoa2028631.

  PMID: 34192431 BACKGROUND

• Suzuki K, Wechalekar AD, Kim K, Shimazaki C, Kim JS, Ikezoe T, Min CK, Zhou F, Cai Z, Chen X, Iida S, Katoh N, Fujisaki T, Shin HJ, Tran N, Qin X, Vasey SY, Tromp B, Weiss BM, Comenzo RL, Kastritis E, Lu J. Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA. Ann Hematol. 2023 Apr;102(4):863-876. doi: 10.1007/s00277-023-05090-z. Epub 2023 Mar 2.

  PMID: 36862168 BACKGROUND

• Minnema MC, Dispenzieri A, Merlini G, Comenzo RL, Kastritis E, Wechalekar AD, Grogan M, Witteles R, Ruberg FL, Maurer MS, Tran N, Qin X, Vasey SY, Weiss BM, Vermeulen J, Jaccard A. Outcomes by Cardiac Stage in Patients With Newly Diagnosed AL Amyloidosis: Phase 3 ANDROMEDA Trial. JACC CardioOncol. 2022 Nov 15;4(4):474-487. doi: 10.1016/j.jaccao.2022.08.011. eCollection 2022 Nov.

  PMID: 36444227 BACKGROUND

• Sanchorawala V, Palladini G, Minnema MC, Jaccard A, Lee HC, Gibbs S, Mollee P, Venner C, Lu J, Schonland S, Gatt M, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Chauveau D, Gries KS, Fastenau J, Tran NP, Qin X, Vasey SY, Weiss BM, Vermeulen J, Ho KF, Merlini G, Comenzo RL, Kastritis E, Wechalekar AD. Health-related quality of life in patients with light chain amyloidosis treated with bortezomib, cyclophosphamide, and dexamethasone +/- daratumumab: Results from the ANDROMEDA study. Am J Hematol. 2022 Jun 1;97(6):719-730. doi: 10.1002/ajh.26536. Epub 2022 Mar 30.

  PMID: 35293006 BACKGROUND

• Wechalekar AD, Cibeira MT, Gibbs SD, Jaccard A, Kumar S, Merlini G, Palladini G, Sanchorawala V, Schonland S, Venner C, Boccadoro M, Kastritis E. Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group. Amyloid. 2023 Mar;30(1):3-17. doi: 10.1080/13506129.2022.2093635. Epub 2022 Jul 15.

  PMID: 35838162 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

whole blood, urine, bone marrow

MeSH Terms

Interventions

daratumumab; Bortezomib; Dexamethasone; dapagliflozin

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 7, 2024
• Study Start: March 15, 2024
• Primary Completion: January 30, 2025
• Study Completion: December 31, 2025
• Last Updated: March 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share