Orelabrutinib combined with BR/G for untreated Marginal Zone Lymphoma

Orelabrutinib Combined With BR/G Followed by Orelabrutinib Maintenance Therapy for Newly Diagnosed Marginal Zone Lymphoma (MZL): A Prospective ,Multicenter, Clinical Study

This study is testing if a new drug called Orelabrutinib, combined with other treatments, can help younger and older patients with untreated Marginal Zone Lymphoma feel better and have fewer side effects.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 69 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: First Affiliated Hospital of Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, rituximab, Obinutuzumab, Orelabrutinib
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06504940 on ClinicalTrials.gov

What this trial studies

This multi-center, prospective cohort study evaluates the efficacy and safety of Orelabrutinib in combination with either bendamustine and rituximab (BR) for younger patients or obinutuzumab (G) for older patients with untreated Marginal Zone Lymphoma (MZL). Cohort A includes patients aged 18-70 who are fit for chemotherapy, while Cohort B focuses on patients aged 70 and older or those under 70 who are unfit for chemotherapy. The study aims to explore effective, low-toxicity treatment options for MZL, a type of B-cell malignancy, by utilizing new drug regimens that include a BTK inhibitor. Patients achieving a partial response or better will continue on Orelabrutinib monotherapy maintenance therapy.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 18-70 with good physical fitness or those aged 70 and older or unfit for chemotherapy with confirmed Marginal Zone Lymphoma.

Not a fit: Patients with other types of lymphoma or those who have previously received treatment for Marginal Zone Lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective and less toxic option for patients with Marginal Zone Lymphoma.

How similar studies have performed: Other studies have shown promising results with BTK inhibitors in treating Marginal Zone Lymphoma, indicating a potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. For Cohort A: Age 18-70 years, physical condition assessed by a physician as suitable for chemotherapy; for Cohort B: Age 70 or older or under 70 years of age assessed by a physician as unsuitable for chemotherapy.
2. Gender is not limited.
3. Confirmed by histopathology, marginal zone lymphoma including MALT, SMZL, NMZL.
4. Progression, recurrence after local treatment, or unsuitable for local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment).
5. ECOG performance score 0-3 points (if the score is 3 points, the physician needs to assess that the deterioration of physical condition is mainly due to tumor burden).
6. Indications for treatment (with B symptoms, blood cell decline, bleeding, large mass, rapid progression of tumors, etc.).
7. Major organ functions meet the following criteria: a) Complete blood count: Absolute neutrophil count ≥1.5×10\^9/L, platelets ≥75×10\^9/L, hemoglobin ≥75g/L; if accompanied by bone marrow involvement, absolute neutrophil count ≥1.0×10\^9/L, platelets ≥50×10\^9/L, hemoglobin ≥50g/L. b) Blood biochemistry: Total bilirubin ≤1.5 times the upper limit of normal (ULN), AST or ALT ≤2 times ULN; serum creatinine ≤1.5 times ULN; serum amylase ≤ULN. c) Coagulation function: International normalized ratio (INR) ≤1.5 times ULN.
8. Life expectancy ≥3 months.
9. Voluntarily sign a written informed consent form before the trial screening.

Exclusion Criteria:

1. Currently or previously have other malignant tumors, unless radical treatment has been performed and there is evidence of no recurrence or metastasis within the last 5 years.
2. Lymphoma involving the central nervous system or transformation to a higher grade.
3. Have uncontrollable or significant cardiovascular diseases, including: a) Within 6 months before the first administration of the study drug, there is a history of New York Heart Association (NYHA) class II or above congestive heart failure, unstable angina, myocardial infarction, or arrhythmias requiring treatment at the time of screening, with a left ventricular ejection fraction (LVEF) \<50%. b) Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy). c) A history of clinically significant QTc interval prolongation, or a QTc interval \>470ms in females and \>450ms in males during the screening period. d) Symptomatic or medication-requiring coronary artery heart disease subjects. e) Subjects with uncontrollable hypertension (despite lifestyle improvements and the use of reasonable, tolerable, and adequate doses of three or more antihypertensive drugs, including diuretics, for more than 1 month, blood pressure is still not at the standard, or it is only effectively controlled when taking four or more antihypertensive drugs).
4. Active bleeding within 2 months before screening, or currently taking anticoagulant drugs, or the investigator believes there is a clear bleeding tendency.
5. History of deep vein thrombosis or pulmonary embolism within the past six months.
6. Clinically significant gastrointestinal abnormalities that may affect the intake, transport, or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction), or subjects who have undergone total gastrectomy.
7. History of organ transplantation or allogeneic bone marrow transplantation.
8. Major surgery within 6 weeks before screening or minor surgery within 2 weeks before screening. Major surgery is surgery that uses general anesthesia, but endoscopic examinations for diagnostic purposes are not considered major surgery. Insertion of vascular access devices will be exempt from this exclusion criterion.
9. Active infection or uncontrolled HBV (positive for HBsAg and/or HBcAb with positive HBV DNA titer), positive for HCV Ab, HIV/AIDS, or other serious infectious diseases; define active infection.
10. Subjects currently with pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, etc., that seriously affect lung function.
11. Previously treated with BTK, BCR pathway inhibitors (such as PI3K, Syk), and BCL-2 inhibitors.
12. Pregnant, breastfeeding women, and subjects of childbearing age who are unwilling to take contraceptive measures.
13. Need to continuously take drugs with moderate to severe inhibitory effects on cytochrome P450 CYP3A or strong inductive effects.
14. Other situations deemed unsuitable for participating in this trial by the investigator.

Where this trial is running

Hangzhou, Zhejiang

• The First Affiliated Hospital ，Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Xuewu Zhang

Conditions Marginal Zone Lymphoma; orebrutinib; BTKi