Selinexor, Daratumumab, and Dexamethasone (XDd) for Light-Chain Cardiac Amyloidosis

August 12, 2026 updated by: Yini Wang, Beijing Anzhen Hospital

Selinexor Combined With Daratumumab and Dexamethasone (XDd) for the Treatment of Patients With Advanced Light-Chain Cardiac Amyloidosis: A Prospective, Multicenter, Phase II Clinical Study

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 Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

63

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: XDd
Drug: XDd

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Hematologic complete response rate
Time Frame: From enrollment to the end of treatment at 1 year
From enrollment to the end of treatment at 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac organ response rate
Time Frame: From enrollment to the end of treatment at 1 year
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
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.
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
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.
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.
From first dose until date of death from any cause, assessed up to 12 months.
Quality of life assessed by EORTC QLQ-C30
Time Frame: 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)
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
From the first dose through 28 days after the last dose
Biomarker Outcome: dFLC
Time Frame: 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).
Baseline and every 4 weeks during treatment, up to 12 months.
Biomarker outcome: NT-proBNP
Time Frame: 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)
Baseline and every 4 weeks during treatment, up to 12 months.
Biomarker outcome: MRD
Time Frame: 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).
Baseline and at end of treatment, up to 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Anzhen Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 13, 2026

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

July 13, 2026

First Submitted That Met QC Criteria

July 29, 2026

First Posted (Actual)

August 4, 2026

Study Record Updates

Last Update Posted (Actual)

August 13, 2026

Last Update Submitted That Met QC Criteria

August 12, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

  • XDd-LCA-Phase2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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