BR Combined With OR in Treatment-naïve Marginal Zone Lymphoma

NCT07008053 | Not Yet Recruiting Phase 2

• 1 other identifier: BROAD
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multi-center, prospective study. The main purpose is to evaluate the efficacy and safety of BR (bendamustine and zuberitamab) combined with OR (orelabrutinib and zuberitamab) in treatment-naïve patients with marginal zone lymphoma.

Conditions

Marginal Zone Lymphomas

Keywords

Lymphoma、Marginal zone lymphoma、Orelabrutinib; Bendamustine; Zuberitamab

Outcome Measures

Primary Outcomes (1)

• Complete response rate

  Complete response rate is defined as the proportion of patients with a response of CR.

  From enrollment to the end of induction therapy of cycle 6 (each cycle is 28 days)

Secondary Outcomes (6)

• Overall response rate (ORR)

  At the end of induction therapy (6 cycles; each cycle is 28 days)

• Time to response (TTR)

  From the start of therapy to the first documentation of response, assessed up to 3 years.

• Duration of Response (DOR)

  From the first demonstration of response until disease progression/death, up to 3 years

• Progression-free survival (PFS)

  From the date of enrollment until the date of first documented progression, up to 3 years

• Overall survival (OS)

  From the date of enrollment until the date of death, up to 3 years

Study Arms (1)

BR (bendamustine and zuberitamab) + OR (orelabrutinib and zuberitamab)

EXPERIMENTAL

Induction therapy: patients will receive 90 mg/m2 of bendamustine and 375 mg/m2 zuberitamab from cycles 1 to 3, followed by 150 mg of orelabrutinib and 375 mg/m2 zuberitamab from cycles 4 to 6. Maintenance therapy: at the investigator's discretion, patients who achieved a complete response or partial response could be assigned to maintenance therapy, consisting of 150 mg of orelabrutinib for 24 cycles.

Drug: BR+OR

Interventions

BR+OR DRUG

Patients who meet the inclusion criteria will enter the treatment period, which consists of an induction phase followed by a maintenance phase. During the induction treatment period, a combined treatment of 3 cycles of the BR regimen and 3 cycles of the OR regimen will be administered, every 28-day cycle for 6 cycles. After the induction treatment, the efficacy assessment will determine whether patients with CR or PR proceed to the maintenance treatment period. Orelabrutinib monotherapy will used as maintenance therapy, every 28-day cycle for up to 24 cycles, or until disease progression/recurrence, unacceptable toxicity, death or consent withdrawal.

BR (bendamustine and zuberitamab) + OR (orelabrutinib and zuberitamab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years, gender not limited;
• Histopathologically confirmed CD20-positive marginal zone lymphoma including MALT, SMZL, NMZL;
• At least one measurable lesion;
• Ann Arbor stage II includes abdominal or intestinal tumor invasion, stage III and IV have indications for treatment (e.g. B symptoms, decreased blood cells, bleeding, large masses, rapid tumor progression);
• Without systemic treatment, MZL that has progressed, recurred, or is not suitable for local treatment after previous local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment, and CD20 monoclonal antibody monotherapy);
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• Major organ function meets 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 invasion, absolute neutrophil count ≥1.0×10\^9/L, platelets ≥50×10\^9/L, hemoglobin ≥50g/L; b) Blood biochemistry: Total bilirubin ≤1.5 ULN, AST or ALT ≤2 ULN; serum creatinine ≤1.5 ULN;
• Coagulation function: International normalized ratio (INR) ≤1.5 ULN;
• Expected survival time ≥12 months;
• Voluntarily sign a written informed consent form before the trial screening.

You may not qualify if:

• Currently or previously diagnosed with other malignant tumors, unless curative treatment has been performed and there is evidence of no recurrence or metastasis within the last 5 years;
• Lymphoma involving the central nervous system or transformation to a higher grade;
• Have uncontrolled or significant cardiovascular disease: a) Within 6 months prior to the first dose of the study drug, there was New York Heart Association (NYHA) Class II or above congestive heart failure, unstable angina, myocardial infarction, or any arrhythmia requiring treatment at screening, with a left ventricular ejection fraction (LVEF)\<50%; b) Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, or unclassified cardiomyopathy); c) History of clinically significant QTc interval prolongation, or QTc interval \>470 ms for females and \>450 ms for males during the screening period; d) Subjects with symptomatic or pharmacologically treated coronary artery disease; e) Subjects with uncontrolled hypertension (blood pressure not reaching target despite lifestyle modifications and the use of reasonable, tolerable doses of 3 or more antihypertensive drugs (including diuretics) for over 1 month, or blood pressure only effectively controlled with 4 or more antihypertensive drugs.
• Active bleeding within 2 months prior to screening, or currently taking anticoagulant medications, or the investigator considers there to be a definite bleeding tendency;
• History of deep vein thrombosis or pulmonary embolism within the past six months.
• Major surgery within 6 weeks prior to screening or minor surgery within 2 weeks prior to screening. Major surgery is defined as any surgical procedure that requires general anesthesia, except endoscopic procedures performed for diagnostic purposes, which are not considered major surgery
• Active infection or uncontrolled HBV (positive for HBsAg and/or HBcAb and positive for HBV DNA titer), HCV Ab positive, HIV/AIDS, or other serious infectious diseases;
• Patients currently have pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, or other conditions affecting lung function；
• Pregnant or lactating women and women of childbearing age who are unwilling to take contraceptive measures;
• Need to continuously take drugs with moderate to severe inhibitory or strong inductive effects on cytochrome P450 CYP3A;
• Other conditions that the investigator considers unsuitable for participating in this trial.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (6)

Fujian Cancer Hospital

Fuzhou, Fujian, China

Location

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Shandong Cancer Hospital

Jinan, Shandong, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, China

Location

Study Officials

• Huilai Zhang

  Tianjin Medical University Cancer Institute and Hospital

  STUDY DIRECTOR

Central Study Contacts

Tianjin Medical University Cancer Institute and Hospital

CONTACT

022-23340123; zhlwgq@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2025
• First Posted: June 6, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: June 6, 2025

Record last verified: 2025-05

Locations

CN (6)