The goal of this clinical trial is to evaluate whether selinexor combined with daratumumab and dexamethasone (XDd) can treat patients with advanced light-chain cardiac amyloidosis. The main questions it aims to answer are: Does XDd regimen achieve hematologic complete response in patients with advanced light-chain cardiac amyloidosis? Does XDd regimen improve cardiac response, organ response, progression-free survival, overall survival, quality of life, and safety?
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Selinexor (X): 40 mg orally once weekly (QW) Daratumumab (D): 1800 mg per dose, subcutaneous injection; administered once weekly during cycles 1-2, once every 2 weeks during cycles 3-6, and once every 4 weeks from cycle 7 onward. One cycle is 4 weeks. Dexamethasone (d): 20-40 mg once weekly (QW)
Hematologic complete response rate
Time frame: From enrollment to the end of treatment at 1 year
Cardiac organ response rate
Time frame: From enrollment to the end of treatment at 1 year
Organ response rate (heart, kidney, and liver)
Time frame: From enrollment to the end of treatment at 1 year
Duration of response
Time frame: From first documented response until documented progression or death, assessed up to 1 years.
Time to response
Time frame: From first dose until first documented response, assessed up to 1 years
Progression-free survival
Time frame: From first dose until date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.
Overall survival
Time frame: From first dose until date of death from any cause, assessed up to 12 months.
Quality of life assessed by EORTC QLQ-C30
Mean change from baseline in EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global health status/Quality of life score (range 0-100; higher scores indicate better quality of life)
Time frame: Through study completion, up to 1 year.
Incidence and Severity of Adverse Events
Time frame: From the first dose through 28 days after the last dose
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Biomarker Outcome: dFLC
Change from baseline in difference between involved and uninvolved free light chains (dFLC) (mg/L).
Time frame: Baseline and every 4 weeks during treatment, up to 12 months.
Biomarker outcome: NT-proBNP
Change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (pg/mL)
Time frame: Baseline and every 4 weeks during treatment, up to 12 months.
Biomarker outcome: MRD
Minimal residual disease (MRD) status in bone marrow (assessed by multiparameter flow cytometry of bone marrow).
Time frame: Baseline and at end of treatment, up to 12 months.