Clinical trial NCT06513234: Combination of Orelabrutinib and Obinutuzumab in Untreated Marginal Zone Lymphomas
Official title: Orelabrutinib Combined With Obinutuzumab as First-line Treatment for Marginal Zone Lymphoma：a Prospective Single Arm Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Marginal Zone Lymphoma
Keywords: Marginal Zone Lymphomas
orelabrutinib
obinutuzumab
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2024-07-22
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective single arm phase II study, and the purpose of this study is to evaluate the safety and efficacy of orelabrutinib combined with obinutuzumab a in untreated marginal zone lymphoma. It is planned to recruit 45 patients. The primary endpoint is the complete remission rate at 12 months.

Detailed description: Marginal zone lymphomas (MZL) are a type of lymphoma that originates from the marginal zone tissue of the lymphoid follicles (Mucosa-associated lymphoid tissue, MALT), and include three subtypes: MALT lymphoma, nodal MZL, and splenic MZL. For patients with marginal zone lymphoma who have indications for systemic anti-tumor treatment, therapeutic options include rituximab monotherapy or more intensive immunochemotherapy regimens in combination with bendamustine, chlorambucil, CHOP regimen (cyclophosphamide, vincristine, doxorubicin, prednisone), etc.

This is a prospective, phase II, single-arm clinical study to initially explore the efficacy and safety of Orelabrutinib combined with obinutuzumab in patients with previously untreated marginal zone lymphoma. The patients will be treated with 6 cycles of OG regimen. Patients with CR/PR after 6 cycles of OG treatment will be treated with 18 cycles of single-agent orelabrutinib regimen.

Eligibility criteria: Inclusion Criteria:

* • Age ≥18 years, gender unrestricted;

  * Histopathologically confirmed CD20-positive marginal zone lymphoma including MALT, SMZL, NMZL;
  * MZL that has progressed, recurred, or is unsuitable for local treatment after previous local therapy (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment);
  * ECOG performance status score of 0-2.
  * 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.

Exclusion Criteria:

* Currently or previously having 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 transforming into a higher grade;
* Having uncontrollable or significant cardiovascular diseases, including: a) New York Heart Association (NYHA) class II or above congestive heart failure, unstable angina, myocardial infarction within 6 months before the first administration of the study drug, or arrhythmias requiring treatment at the time of screening, with a left ventricular ejection fraction (LVEF) \&lt;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 \&gt;470ms in females and \&gt;450ms in males during the screening period; d) Subjects with symptomatic or medication-requiring coronary artery heart disease; e) Subjects with difficult-to-control hypertension (despite lifestyle improvements and the use of reasonable, tolerable, and adequate doses of one or 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 definite bleeding tendency;
* 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.
* Any other conditions deemed unsuitable for participation in this trial by the investigator.

Primary outcomes:
measure: the complete response rate
timeFrame: At 12 months.
Secondary outcomes:
measure: CRR
timeFrame: At the end of induction therapy(6cycles). 28days/cycle
measure: ORR
timeFrame: At 12 months.
measure: BOR
timeFrame: At 12 months.
measure: 2 years progression-free survival
timeFrame: 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
measure: 2 years overall survival
timeFrame: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years]
measure: TTR
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: The occurrence of adverse events and serious adverse events
timeFrame: One month after discontinuation of treatment
Other outcomes:
Locations:
city: Tianjin
country: China
facility: China Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
Study officials:
References: