The Efficacy and Safety of Sonrotoclax, Zanubrutinib Combined With Obinutuzumab in MCL

Official title

A Single-Arm, Prospective Clinical Study Evaluating the Efficacy and Safety of Sonrotoclax and Zanubrutinib Combined With Obinutuzumab in the First-Line Treatment of Newly Diagnosed Intermediate-to-High-Risk Mantle Cell Lymphoma

Overview

A Single-Arm, Prospective Clinical Study Evaluating the Efficacy and Safety of Sonrotoclax, Zanubrutinib Combined with Obinutuzumab in the First-Line Treatment of Newly Diagnosed Intermediate-to-High-Risk Mantle Cell Lymphoma

Interventions

• Drug Sonrotoclax, Zanubrutinib Combined with Obinutuzumab
  The treatment regimen was as follows: In cycle 1 (C1), obinutuzumab 1000 mg was administered intravenously on day 1 (D1); sotoroclax was given at 80 mg on D2, 160 mg on D3, and 320 mg on D4; zanubrutinib was administered at 160 mg twice daily (BID). Each cycle was defined as 28 days. From cycles 2 to 6 (C2-C6), patients received obinutuzumab 1000 mg intravenously on D1, sotoroclax 320 mg once daily, and zanubrutinib 160 mg BID.

Primary outcome measures

• Complete response rate [Time frame: At the end of Cycle 6 (each cycle is 28 days)]

Secondary outcome measures (4)

• Overall survival [Time frame: 2 years after enrollment]
• Overall response rate [Time frame: Overall Response Rate At the end of Cycle 6 (each cycle is 28 days)]
• Progression free survival [Time frame: 2 years after enrollment]
• Treatment-Related Adverse Events [Time frame: From enrollment to study completion, a maximum of 3 years.]

Eligibility criteria

Inclusion criteria

• Age ≥18 years.
• Histologically confirmed, previously untreated mantle cell lymphoma (MCL), with at least one of the following high-risk features:

• Blastoid or pleomorphic morphology;
• Ki-67 ≥30%;
• TP53 mutation or deletion;
• 17p deletion;
• High-risk MIPI group with an expected survival >3 months.
• Laboratory criteria meeting the following requirements:

• Absolute neutrophil count ≥1,000/mm³ or ≥1.0 × 10⁹/L, platelet count ≥50,000/mm³ or ≥50 × 10⁹/L, and hemoglobin ≥8 g/dL;
• Creatinine clearance ≥50 mL/min (calculated using the standard Cockcroft-Gault formula);
• Serum albumin ≥3.0 g/dL; total bilirubin ≤1.5 × the upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or ≤5.0 × ULN in cases of hepatic lymphoma involvement; serum amylase or lipase ≤ULN;
• International normalized ratio (INR) ≤1.5 × ULN or activated partial thromboplastin time (aPTT) ≤1.5 × ULN; for patients receiving warfarin anticoagulation therapy, INR may be between 2 and 3;
• Cardiac function: left ventricular ejection fraction (LVEF) ≥50%.

Exclusion criteria

• Contraindications to any of the study drugs.
• Known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis (hepatitis B defined as positive hepatitis B core antibody \[HBcAb\] with HBV-DNA above the ULN; active hepatitis C defined as positive HCV antibody-patients with negative HCV-RNA may be enrolled).
• Human immunodeficiency virus (HIV) infection.
• Congestive heart failure (New York Heart Association \[NYHA\] Class >2); history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to enrollment.
• Congenital long QT syndrome or QTc >480 ms (QTc must be calculated using Fridericia's formula: QTcF = QT/(RR)\^0.33).
• History of other malignancies within the past 5 years, except for cured carcinoma in situ of the cervix, basal cell carcinoma of the skin, carcinoma in situ of the breast, or other second primary malignancies that were curatively treated and have had no recurrence within 5 years.
• Pregnant or breastfeeding women, or those planning to become pregnant during the study period (fertile men and women must agree to use effective contraception during the study and for 30 days after the last dose of study treatment, such as dual-barrier methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. Postmenopausal women and surgically sterilized women are exempt).
• Prior history of significant neurological or psychiatric disorders, or history of psychotropic drug abuse or substance abuse.
• Clinically significant active infection.
• Inability to take oral medications, difficulty swallowing, chronic diarrhea, intestinal obstruction, or other conditions that may affect drug administration or absorption.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Ruijin Hospital — Shanghai

Identifiers

NCT: NCT07548255 · Solide

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗