Intermediate-to-High-Risk Mantle Cell Lymphoma, the Efficacy and Safety
Conditions
Brief summary
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
DRUGSonrotoclax, 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.
Sponsors
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Histologically confirmed, previously untreated mantle cell lymphoma (MCL), with at least one of the following high-risk features: 1. Blastoid or pleomorphic morphology; 2. Ki-67 ≥30%; 3. TP53 mutation or deletion; 4. 17p deletion; 5. High-risk MIPI group with an expected survival \>3 months. 3. Laboratory criteria meeting the following requirements: 1. 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; 2. Creatinine clearance ≥50 mL/min (calculated using the standard Cockcroft-Gault formula); 3. 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; 4. 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; 5. Cardiac function: left ventricular ejection fraction (LVEF) ≥50%.
Exclusion criteria
1. Contraindications to any of the study drugs. 2. 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). 3. Human immunodeficiency virus (HIV) infection. 4. 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. 5. Congenital long QT syndrome or QTc \>480 ms (QTc must be calculated using Fridericia's formula: QTcF = QT/(RR)\^0.33). 6. 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. 7. 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). 8. Prior history of significant neurological or psychiatric disorders, or history of psychotropic drug abuse or substance abuse. 9. Clinically significant active infection. 10. Inability to take oral medications, difficulty swallowing, chronic diarrhea, intestinal obstruction, or other conditions that may affect drug administration or absorption.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate | At the end of Cycle 6 (each cycle is 28 days) | The percentage of participants with a complete response at the end of Cycle 6 was determined on the basis of investigator assessments according to the Lugano Classification for Response Criteria in Lymphoma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 2 years after enrollment | Overall survival (OS) was measured from the date of diagnosis to the date of death or the last follow-up. |
| Overall response rate | Overall Response Rate At the end of Cycle 6 (each cycle is 28 days) | The percentage of participants with overall response was determined on the basis of investigator assessments according to the Lugano Classification for Response Criteria in Lymphoma |
| Progression free survival | 2 years after enrollment | Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, or death from any cause, whichever occurred first. |
| Treatment-Related Adverse Events | From enrollment to study completion, a maximum of 3 years. | An adverse event is any untoward medical occurrence in a participant receiving a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease that is temporally associated with the use of a pharmaceutical product, whether or not it is considered related to the pharmaceutical product. Preexisting conditions that worsen during a study are also considered adverse events. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. |
Countries
China
Contacts
CONTACTWeili Zhao
Outcome results
None listed