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

NCT07335887 | Recruiting Phase 2

• 1 other identifier: 2025PHD030-002
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

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)

• hematological ≥VGPR rate within four cycles of induction 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 (14)

• 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 (3)

• 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)

• Correlation analysis between different MRD status groups and MOD-PFS, PFS and OS

  1 year

Study Arms (1)

Sond±D

EXPERIMENTAL

Cohort A: (sample size 20) sonrotoclax combined with daratumumab and dexamethasone in t(11;14) AL amyloidosis, newly diagnosed or previously untreated with anti-CD38 mAb therapy. Cohort B: (sample size 19) sonrotoclax combined with dexamethasone in t(11;14) AL patients insensitive to or relapsed after anti-CD38 mAb therapy All patients will receive up to 12 cycles therapy until major organ deterioration (MOD)-progression free survival (PFS) event, death, withdrawal of informed consent, need for alternative therapy, intolerance, or study termination, whichever occurs first. Transplant-eligible patients could undergo stem cell collection during induction; autologous transplantation was permitted after completion of the primary endpoint assessment (after cycle 4) at investigator discretion

Drug: sonrotoclax; Drug: Daratumumab; Drug: Dexamethasone

Interventions

sonrotoclax DRUG

cohor A \& Cohort B: Induction therapy (C1-4) : Sonrotoclax once daily A conventional 3+3 design will determine the target sonrotoclax dose during the C1 safety run-in phase. And dose-limiting toxicity (DLT) assessed during a 28-day evaluation window. Patients who are enrolled after the safety run-in phase will receive sonrotoclax at the dose determined in safety run-in phase. A 3-day ramp-up is used (320 mg: 80→160→320 mg on D1-D3; 640 mg: 160→320→640 mg on D1-D3) in C1, with the Day 3 dose maintained from Day 4 onward for all patients. Subsequent therapy (C5-12) Sonrotoclax once daily (same dose as in the induction phase)

Also known as: BGB-11417

Sond±D

Daratumumab DRUG

Cohor A Only Daratumumab (16 mg/kg intravenously) or daratumumab and hyaluronidase-fihj (1800 mg subcutaneously）once weekly C1-2; every two weeks C3-6; every month C7-12

Sond±D

Dexamethasone DRUG

cohor A \& Cohort B: 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

Study Sites (3)

Peking University First Hospital

Beijing, China

RECRUITING

Peking University People's Hospital

Beijing, China

RECRUITING

The first Affiliated Hospital of Xi'an Jiaotong University

Xi'an, China

NOT YET RECRUITING

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

Central Study Contacts

Yang Liu

CONTACT

+86 13716926210; pkuphliuyang@bjmu.edu.cn

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: February 10, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: July 28, 2026

Record last verified: 2026-07

Locations

CN (3)