Optimize Study - Orelabrutinib Combined With BR/G in Untreated Marginal Zone Lymphoma (MZL)

NCT06504940 | Recruiting Phase 2

• 1 other identifier: IIT20240202
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, prospective cohort study. The main purpose of Cohort A is to evaluate the efficacy and safety of Orelabrutinib combined with BR (bendamustine and rituximab) for previously untreated young patients with MZL; the purpose of Cohort B is to assess the efficacy and safety of Orelabrutinib combined with G (Obinutuzumab) followed by Orelabrutinib maintenance therapy for previously untreated elderly patients with MZL.

Conditions

Marginal Zone Lymphoma

Keywords

orebrutinib; BTKi; Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (2)

• Cohort A:the complete response rate (CRR)

  CRR is defined as the proportion of patients with a response of CR

  At 3 months.

• Cohort B: CRR

  CRR is defined as the proportion of patients with a response of CR

  at 6 months

Secondary Outcomes (7)

• Overall response rate (ORR)

  Up to 2 years

• The 2-year overall survival (OS) rate

  From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years

• The 2-year progression-free survival (PFS) rate.

  From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

• Duration of response

  Up to 2 years

• TTR

  Up to 2 years

Study Arms (2)

Cohort A

EXPERIMENTAL

For individuals under 70 years of age with good fitness,

Drug: Orelabrutinib combined with bendamustine and rituximab

Cohort B

EXPERIMENTAL

For individuals aged 70 or older or those under 70 years with poor fitness

Drug: Orelabrutinib combined with obinutuzumab

Interventions

Orelabrutinib combined with bendamustine and rituximab DRUG

they will receive three cycles of Orelabrutinib combined with bendamustine and rituximab (BR: bendamustine 70mg/m\^2 on days 1-2; rituximab 375mg/m\^2 on day 0). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 21 cycles, each cycle 28 days).

Cohort A

Orelabrutinib combined with obinutuzumab DRUG

they will receive six cycles of Orelabrutinib combined with obinutuzumab (G 1000mg iv on days 1, 8, 15 of cycle 1, and day 1 of cycles 2-6; Orelabrutinib 150mg once daily). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 18 cycles, each cycle 28 days ).

Cohort B

Eligibility Criteria

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

You may qualify if:

• 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.
• Gender is not limited.
• Confirmed by histopathology, marginal zone lymphoma including MALT, SMZL, NMZL.
• Progression, recurrence after local treatment, or unsuitable for local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment).
• 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).
• Indications for treatment (with B symptoms, blood cell decline, bleeding, large mass, rapid progression of tumors, etc.).
• 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.
• Life expectancy ≥3 months.
• Voluntarily sign a written informed consent form before the trial screening.

You may not qualify if:

• 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.
• Lymphoma involving the central nervous system or transformation to a higher grade.
• 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).
• Active bleeding within 2 months before screening, or currently taking anticoagulant drugs, or the investigator believes there is a clear bleeding tendency.
• History of deep vein thrombosis or pulmonary embolism within the past six months.
• 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.
• History of organ transplantation or allogeneic bone marrow transplantation.
• 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.
• Subjects currently with pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, etc., that seriously affect lung function.
• Previously treated with BTK, BCR pathway inhibitors (such as PI3K, Syk), and BCL-2 inhibitors.
• Pregnant, breastfeeding women, and subjects of childbearing age who are unwilling to take contraceptive measures.
• Need to continuously take drugs with moderate to severe inhibitory effects on cytochrome P450 CYP3A or strong inductive effects.
• Other situations deemed unsuitable for participating in this trial by the investigator.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital ，Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

Bendamustine Hydrochloride; Rituximab; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Xuewu Zhang

CONTACT

+86 15168316013; moyu0718@126.com

Wenjuan Yu

CONTACT

yyu@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 17, 2024
• Study Start: June 28, 2024
• Primary Completion (Estimated): July 8, 2027
• Study Completion (Estimated): July 8, 2029
• Last Updated: February 27, 2026

Record last verified: 2025-07

Locations

CN (1)