Marginal Zone Lymphoma
Conditions
Keywords
Lymphoma, Marginal zone lymphoma, Orelabrutinib
Brief summary
This is a single-arm, multicenter, prospective, phase II study. The primary objective is to assess the efficacy and safety of orelabrutinib in treatment-naïve patients with marginal zone lymphoma.
Detailed description
Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies originating from B lymphocytes, primarily occurring in the marginal zones of the spleen, lymph nodes, and mucosa-associated lymphoid tissues. Its histological features are characterized by abnormal proliferation of marginal zone cells surrounding lymphoid follicles. The Bruton tyrosine kinase (BTK) signaling pathway plays a critical role in B-cell receptor-mediated signal transduction and is significant in the development and progression of various B-cell malignancies. Ibrutinib, as the first BTK inhibitor, has demonstrated remarkable efficacy in the treatment of B-cell lymphomas. However, its poor kinase selectivity leads to a high incidence of off-target toxicities, including thrombocytopenia, neutropenia, bleeding, fatigue, rash, and atrial fibrillation in clinical settings, which limits its long-term use. Orelabrutinib is a highly selective oral small-molecule BTK inhibitor belonging to the nicotinamide class of compounds. It covalently binds to BTK and represents a new generation of selective irreversible BTK inhibitors. Due to its higher selectivity for BTK and favorable safety profile observed in previous human studies, orelabrutinib holds promise as a superior therapeutic option for B-cell malignancies. To further improve clinical outcomes for MZL patients, there is an urgent need to explore treatment strategies with better efficacy and lower toxicity. This study aims to evaluate the efficacy and safety of orelabrutinib in previously untreated localized-stage MZL patients, providing new therapeutic evidence for this population. This study is a multicenter, prospective trial involving previously untreated patients with MZL. During the induction phase (cycles 1-6), patients will receive orelabrutinib 150 mg, administered in 28-day treatment cycles. Following completion of the induction phase, patients will be followed during a post-treatment follow-up period.
Interventions
DRUGOrelabrutinib
Induction phase (cycle 1-6): Orelabrutinib (150 mg)
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Beijing Tongren 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, regardless of gender; 2. Patients with histopathologically confirmed stage I/II marginal zone lymphoma; 3. ECOG performance status score of 0-2; 4. Major organ functions meeting the following criteria: 1. Blood tests: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelets ≥75×10\^9/L, hemoglobin ≥75g/L; if accompanied by bone marrow involvement, ANC ≥1.0×10\^9/L, platelets ≥50×10\^9/L, hemoglobin ≥50g/L; 2. Blood biochemistry: Total bilirubin ≤1.5×ULN, AST or ALT ≤2×ULN; serum creatinine ≤1.5×ULN; 5. Coagulation function: International normalized ratio (INR) ≤1.5×ULN; 6. Expected survival time ≥12 months; 7. Voluntary written informed consent signed before trial screening.
Exclusion criteria
1. Lymphoma involving the central nervous system or transformation to high-grade; 2. Uncontrolled or significant cardiovascular diseases, including: 1. New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first dose of the study drug, or arrhythmia requiring treatment at screening, with left ventricular ejection fraction (LVEF) \<50%; 2. Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, or unclassified cardiomyopathy); 3. History of clinically significant QTc interval prolongation, or QTc interval \>470 ms for females or \>450 ms for males at screening; 4. Subjects with symptomatic coronary artery disease requiring medication; 5. Poorly controlled hypertension (failure to achieve target blood pressure after at least one month of lifestyle modification and treatment with three or more antihypertensive drugs, including diuretics, at maximally tolerated doses, or requiring four or more antihypertensive drugs for effective control). 3. Active bleeding within 2 months prior to screening, or current use of anticoagulants, or investigator-determined clear bleeding tendency; 4. History of deep vein thrombosis or pulmonary embolism within the past six months; 5. Urine protein ≥2+ and 24-hour urine protein quantification ≥2 g/24 hours; 6. Clinically significant gastrointestinal abnormalities that may affect drug intake, transport, or absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction), or subjects with total gastrectomy; 7. Current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or other conditions affecting lung function; 8. Pregnant or breastfeeding women, or subjects of childbearing potential unwilling to use contraception; 9. Continuous use of drugs with moderate to strong cytochrome P450 CYP3A inhibition or strong induction effects; 10. Other conditions deemed by the investigator as unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | From the initiation of treatment to the end of induction therapy of cycle 6 (each cycle is 28 days) | The ORR is defined as the proportion of patients with a response of CR or PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | From the initiation of treatment to the end of induction therapy of cycle 6 (each cycle is 28 days) | Complete response rate is defined as the proportion of patients with a response of CR. |
| Time to response (TTR) | 1years | TTR is defined as the time from the start of therapy to the first response. |
| Duration of Response (DOR) | From the first demonstration of response until disease progression/death, up to 1 years | DOR is defined as the time from documentation of response to treatment to the first documentation of tumor progression or death due to any cause, whichever comes first. |
| Progression-free survival (PFS) | From the date of enrollment until the date of first documented progression, up to 2 years | PFS is defined as the time from enrollment to disease progression or death from any cause. For patients who remain alive and progression-free at the data cutoff date, PFS will be censored at the last tumor assessment date. |
| Overall survival (OS) | From the date of the initiation of treatment until the date of death, up to 2 years | OS is defined as the time from the initiation of treatment to death from any cause. Patients alive at the data cutoff date will have their OS censored at the date of the last follow-up. |
| Adverse events (AEs) | From the date of enrollment until the date of death, up to 1 years | AEs will be graded according to the NCI-CTCAE Version 5.0. |
Countries
China
Contacts
CONTACTShuhua Yi
CONTACTLiang Wang
PRINCIPAL_INVESTIGATORShuhua yi
Hematology Hospital, Chinese Academy of Medical Sciences
PRINCIPAL_INVESTIGATORLiang Wang
Beijing Tongren Hospital
Outcome results
None listed