Waldenström Macroglobulinemia (WM)
Conditions
Interventions
Fixed-duration ZS regimen:Combination therapy of Sotoclax and Zanubrutinib.
Zanubrutinib 160 mg will be given twice daily on Days 1 through 28 of each cycle. Sonrotoclax will be administered on Days 1
Sponsors
Southern Medical University Southern Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Provide a signed and dated written Informed Consent Form (ICF) prior to any study-specific procedures, sampling or analyses; be capable of understanding and complying with study requirements. 2.Aged >= 18 years. 3.Confirmed histologic and clinical diagnosis of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM). 4.No prior systemic treatment for WM (plasmapheresis is permitted as an exception); 5.Meet at least one treatment initiation criterion per the Second IWWM Consensus Panel guidelines at study entry: Clinical indications for treatment initiation: Recurrent fever, night sweats, unintentional weight loss, fatigue; Hyperviscosity syndrome; Symptomatic or bulky lymphadenopathy (longest diameter >=5 cm); Symptomatic hepatomegaly and/or splenomegaly; Symptomatic organomegaly and/or organ/tissue infiltration; WM-related peripheral neuropathy; Laboratory indications for treatment initiation: Symptomatic cryoglobulinemia; Cold agglutinin anemia; WM-associated immune hemolytic anemia and/or thrombocytopenia or renal disease; WM-related amyloidosis; Hemoglobin 0.5 g/dL. 7.Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 to 2. 8.Estimated life expectancy >= 6 months. 9.Adequate bone marrow function defined as: (1) Absolute Neutrophil Count (ANC) =750 cells/mm³ (0.75×10?/L). Note: Screening hematology values used to verify ANC eligibility must be obtained =14 days after the last dose of pegfilgrastim (or other pegylated myeloid growth factors) and =7 days after the last dose of filgrastim or other myeloid growth factors. (2) Platelet count >= 50,000 cells/mm³ (50×10?/L), with no growth factor support or platelet transfusion administered within the preceding 7 days. 10.Adequate organ function defined as: (1) Creatinine clearance >= 50 mL/min determined directly via 24-hour urine collection. (2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 90 days after the last sotoclax dose for fertile females and >= 90 days for non-sterilized males.
Exclusion criteria
Exclusion criteria: 1.Central nervous system (CNS) involvement by WM. 2.Disease transformation to aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL). 3.Requirement for ongoing corticosteroid therapy, excluding adrenal replacement therapy. Note: Systemic corticosteroids (excluding adrenal replacement) must be fully tapered/discontinued at least 7 days prior to the first dose of study treatment. 4.Clinically significant cardiovascular disease including any of the following: (1) Myocardial infarction occurring 450 ms on ECG at screening (average of three consecutive centrally reviewed measurements). (5) History of clinically significant arrhythmia (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes). (6) Uncontrolled atrial fibrillation not tapered/discontinued. (7) Left ventricular ejection fraction (LVEF) =160 mmHg or diastolic BP >= 100 mmHg on >=2 consecutive screening readings despite antihypertensive medication. 5.History of another malignancy within <= 2 years prior to study entry (defined as the date of ICF signing), except for: (1) Adequately treated in situ cervical carcinoma. (2) Localized basal cell carcinoma or localized squamous cell carcinoma of the skin. (3) Prostate cancer with Gleason score =6 and stable prostate-specific antigen (PSA) off chemotherapy. (4) Prior malignancy treated with curative local therapy (surgery or other modalities) with no evidence of disease before first study dose and unlikely to impact survival during study participation. 6.Inability to swallow capsules/tablets or any gastrointestinal disorder including malabsorption syndrome, prior gastrectomy/small bowel resection, bariatric surgery, inflammatory bowel disease, or bowel obstruction. 7.Uncontrolled active systemic infection or recent infection requiring parenteral antimicrobial therapy completed within 14 days prior to first study dose. 8.Any life-threatening illness, medical condition, organ dysfunction, requirement for therapeutic full-dose anticoagulation, or bleeding diathesis that, in the Investigator’s judgment, may compromise patient safety or introduce unacceptable study risk. 9.History of or active human immunodeficiency virus (HIV) infection (HIV-seropositive patients with persistently undetectable viral load are eligible). 10.Serologic evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: (1) Positive hepatitis B surface antigen (HBsAg) or positive hepatitis B core antibody (HBcAb). HBcAb-positive/HBsAg-negative patients are eligible if HBV DNA is undetectable and the patient agrees to monthly HBV reactivation monitoring. (2) Pos
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of VGPR (Very Good Partial Response) or CR (Complete Response); | — |
Secondary
| Measure | Time frame |
|---|---|
| Major Response Rate(MRR);Adverse Event;Progression-Free Survival (PFS); | — |
Countries
China
Contacts
Public ContactXiaolei Wei
Southern Medical University Southern Hospital
Outcome results
None listed