Light-chain Cardiac Amyloidosis
Conditions
Brief summary
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?
Interventions
DRUGXDd
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)
Sponsors
Beijing Anzhen Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * Confirmed systemic light-chain amyloidosis, meeting both of the following: 1. Tissue biopsy confirms amyloid deposition, and the amyloid precursor protein is immunoglobulin light chain or heavy-light chain. Pathologic evidence includes at least one of the following: Congo red staining positive with apple-green birefringence under polarized light microscopy; Light-chain restricted expression demonstrated by immunohistochemistry, immunofluorescence, or immunoelectron microscopy, or mass spectrometry confirming the precursor protein as immunoglobulin light chain; Electron microscopy showing nonbranching, rigid, randomly arranged fibrils with a diameter of 8 to 14 nm. 2. Evidence of monoclonal immunoglobulin or free light chain in serum or urine, or detection of monoclonal plasma cells/B cells in bone marrow examination. * Clinical manifestations, physical examination, laboratory tests, or imaging studies confirm involvement of one or more organs, with mandatory cardiac involvement. Cardiac involvement is defined as either: 1. Mean ventricular wall thickness \> 12 mm on echocardiography, with other cardiac diseases excluded; or 2. NT-proBNP \> 332 ng/L in the absence of renal insufficiency and atrial fibrillation. * Mayo 2004 stage IIIa or IIIb disease, including newly diagnosed and relapsed/refractory patients. * Measurable disease in light-chain amyloidosis, defined by at least one of the following: 1. Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis and immunofixation performed by the central laboratory; 2. Serum free light chain ≥ 50 mg/L with an abnormal kappa/lambda ratio; or 3. Difference between involved and uninvolved free light chains (dFLC) ≥ 50 mg/L. Note: Urine Bence Jones proteinuria alone is not sufficient to define measurable disease for eligibility. * Not pregnant or breastfeeding. Men and women of childbearing potential must agree to use appropriate contraception before treatment, during treatment, during any treatment interruption, and for 4 weeks after treatment completion. * Written informed consent has been signed by the participant. If the participant is unable to sign because of their medical condition, informed consent may be signed by a legal guardian or immediate family member.
Exclusion criteria
* Active hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, or other acquired or congenital immunodeficiency disorders. * Baseline peripheral neuropathy or neuropathic pain of grade ≥ 2 according to NCI CTCAE v4.0. * Major surgery within 30 days before enrollment. * Epilepsy requiring medication, dementia, or other psychiatric conditions that prevent understanding of or compliance with the study protocol. * Any severe physical or psychiatric illness that may interfere with participation in this clinical study. * Any other condition that the investigator considers unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hematologic complete response rate | From enrollment to the end of treatment at 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac organ response rate | From enrollment to the end of treatment at 1 year | — |
| Organ response rate (heart, kidney, and liver) | From enrollment to the end of treatment at 1 year | — |
| Duration of response | From first documented response until documented progression or death, assessed up to 1 years. | — |
| Time to response | From first dose until first documented response, assessed up to 1 years | — |
| Progression-free survival | 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 | From first dose until date of death from any cause, assessed up to 12 months. | — |
| Quality of life assessed by EORTC QLQ-C30 | Through study completion, up to 1 year. | 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) |
| Incidence and Severity of Adverse Events | From the first dose through 28 days after the last dose | — |
| Biomarker Outcome: dFLC | Baseline and every 4 weeks during treatment, up to 12 months. | Change from baseline in difference between involved and uninvolved free light chains (dFLC) (mg/L). |
| Biomarker outcome: NT-proBNP | Baseline and every 4 weeks during treatment, up to 12 months. | Change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (pg/mL) |
| Biomarker outcome: MRD | Baseline and at end of treatment, up to 12 months. | Minimal residual disease (MRD) status in bone marrow (assessed by multiparameter flow cytometry of bone marrow). |
Contacts
CONTACTYini Wang
Outcome results
None listed