Sonrotoclax Plus Dexamethasone With or Without Daratumumab Regimen in Patients With t(11;14) Primary AL Amyloidosis

NCT07335887 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025PHD030-002
• Study Type: interventional
• Target: 39
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this study is to evaluate the efficacy and safety of Sonrotoclax combined Regimen in patients with t(11;14) AL amyloidosis. Participants will receive the Sonrotoclax Plus Dexamethasone regimen with or without Daratumumab for 12 cycles. The Hematologic Response, Organ Response, Survival, and Safety will be evaluated.

Conditions

AL Amyloidosis (AL); t(11;14) Positive

Keywords

sonrotoclax; AL amyloidosis; t(11;14); BCL-2i

Outcome Measures

Primary Outcomes (1)

• Best hematological ≥VGPR rate within four cycles of therapy

  Defined as the proportion of patients achieving VGPR, or CR within four cycles of therapy

  At the end of Cycle 4 (each cycle is 28 days)

Secondary Outcomes (15)

• Hematological ORR after four cycles of therapy

  At the end of Cycle 4 (each cycle is 28 days)

• Hematological CR rate at the end of four cycles of therapy

  at the end of 4 cycles of therapy (each cycle is 28 days)

• Cardiac response rate at the end of 6 cycles of treatment

  At the end of Cycle 6 (each cycle is 28 days)

• Hepatic response rate at the end of 6 cycles of treatment

  At the end of Cycle 6 (each cycle is 28 days)

• Renal response rate at the end of 6 cycles of treatment

  At the end of 6 cycles of treatment (each cycle is 28 days)

Other Outcomes (2)

• MRD negativity rate in patients achieving hematological CR

  1 year

• MRD negativity rate

  At the end of Cycle 9-12 (each cycle is 28 days)

Study Arms (1)

Sond±D

EXPERIMENTAL

Cohort A: sonrotoclax combined with daratumumab and dexamethasone in t(11;14) AL amyloidosis, newly diagnosed or previously untreated with anti-CD38 mAb therapy. Cohort B: sonrotoclax combined with daratumumab and dexamethasone in t(11;14) AL patients insensitive to or relapsed after anti-CD38 mAb therapy

Drug: sonrotoclax; Drug: Daratumumab; Drug: Dexamethasone

Interventions

sonrotoclax DRUG

t(11;14) AL amyloidosis Newly diagnosed or previously untreated with anti-CD38 mAb therapy Induction therapy (C1-4) Sonrotoclax once daily ( dose depends on the 3+3 study design during safety run-in period in C1) Consolidation therapy (C5-12) Sonrotoclax once daily (same as the target dose in induction therapy) t(11;14) AL patients insensitive to or relapsed after anti-CD38 mAb therapy Induction therapy (C1-4) Sonrotoclax once daily (dose depends on the 3+3 study design during safety run-in period in C1) Consolidation therapy (C5-12) Sonrotoclax once daily (same as the target dose in induction therapy)

Also known as: BGB-11417

Sond±D

Daratumumab DRUG

t(11;14) AL patients insensitive to or relapsed after anti-CD38 mAb therapy Daratumumab (16 mg/kg intravenously or 1800 mg subcutaneously, once weekly C1-2; every two weeks C3-6; every month C7-12)

Sond±D

Dexamethasone DRUG

Dexamethasone (40 mg, once weekly) for 12 cycles. The dose was halved for patients 75 years of age or older, and in patients who were intolerant of dexamethasone, as judged by the investigators.

Sond±D

Eligibility Criteria

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

You may qualify if:

• Patients who meet the diagnostic criteria for Primary Systemic Light Chain Amyloidosis (according to the Systemic Light Chain Amyloidosis Diagnosis and Treatment Guidelines (2021 Revision)).
• Age ≥ 18 years.
• Confirmed FISH test result of t(11;14) positive by each center or a third-party laboratory, or a prior FISH test report indicating t(11;14) positivity
• ECOG Performance Status score of 0-2.
• Presence of measurable disease, defined by at least one of the following criteria:
• Serum M-protein ≥ 0.5 g/dL
• Serum free light chain (FLC) level ≥ 40 mg/L with an abnormal kappa/lambda ratio.
• Adequate organ function, defined as:
• Hemoglobin (HGB) \> 80 g/L
• Platelet count \> 50 × 10⁹/L
• Absolute neutrophil count (ANC) \> 1.0 × 10⁹/L
• Total bilirubin ≤ 2.0 × ULN; AST and ALT ≤ 3.0 × ULN
• Creatinine clearance (CrCl) ≥ 30 mL/min
• Oxygen saturation ≥ 90%
• Life expectancy greater than 6 months.

You may not qualify if:

• Meets the diagnostic criteria for active multiple myeloma or active lymphoplasmacytic lymphoma
• Presence of other malignancies at an advanced stage with systemic metastases.
• IgM-type AL amyloidosis.
• Prior treatment with a BCL-2 inhibitor (BCL-2i).
• Presence of any of the following severe cardiovascular diseases
• Mayo 2004 stage IIIb: NT-proBNP \>8500 ng/L.
• NYHA class IIIb-IV
• Left ventricular ejection fraction (LVEF) \<40%.
• QT interval corrected by Fridericia's formula (QTcF) \>480 ms
• Investigator assessment that heart failure is due to ischemic heart disease (e.g., prior history of myocardial infarction with elevated cardiac enzymes and ECG changes) or uncorrected valvular disease, rather than primarily caused by AL amyloidosis.
• Hospitalization for unstable angina or myocardial infarction within 6 months prior to the first dose, or cardiac interventional therapy or coronary artery bypass grafting within 6 months.
• For patients with congestive heart failure, hospitalization for cardiovascular disease within 4 weeks prior to Cycle 1 Day 1.
• History of sustained ventricular tachycardia or aborted ventricular fibrillation, or history of atrioventricular node or sinus node dysfunction requiring a pacemaker/implantable cardioverter-defibrillator (ICD) but not implanted.
• Severe or persistent infection that is not effectively controlled. (Acute infection requiring antibacterial, antifungal, or antiviral therapy that has not resolved within 14 days prior to dosing).
• Positive status for human immunodeficiency virus (HIV) antibody (HIVAb).

Sponsors & Collaborators

• Peking University People's Hospital: lead

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: December 14, 2025
• First Posted: January 13, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: January 13, 2026

Record last verified: 2025-12