Orelabrutinib Combined With Obinutuzumab and Short-Course Venetoclax in Patients With Treatment-Naïve Mantle Cell Lymphoma (MCL)

NCT07719556 | Recruiting Phase 2

• 1 other identifier: 260608
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to evaluate the safety and efficacy of orelabrutinib (O) in combination with obinutuzumab (G) and short-course venetoclax (V) in patients with treatment-naïve MCL.

Conditions

Mantle Cell Lymphoma (MCL)

Keywords

orelabrutinib; MCL; obinutuzumab; venetoclax

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  The CRR is defined as the proportion of patients who achieve a CR following therapy, calculated among all treated patients.

  At the end of induction therapy (6 cycles, 28 days per cycle)

Secondary Outcomes (5)

• MRD negativity rate

  At the end of induction therapy (6 cycles, 28 days per cycle)

• Objective response rate (ORR)

  At the end of induction therapy (6 cycles, 28 days per cycle)

• 2-year progression-free survival (PFS)

  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

• Overall Survival (OS)

  From date of signing the informed consent until the date of death from any cause, whichever came first (up to 3 years)

• The occurrence of adverse events and serious adverse events

  At the end of cycle 24 (28 days per cycle)

Study Arms (1)

orelabrutinib (O) combined with obinutuzumab (G) and short-course venetoclax (V)

EXPERIMENTAL

Induction Phase (6 cycles, 28 days per cycle)： Orelabrutinib + Obinutuzumab \+ Venetoclax. Patients achieving partial response (PR) or complete response (CR) after 3 cycles will receive an additional 3 cycles of induction therapy.Patients with stable disease (SD) or progressive disease (PD) after 3 cycles will be withdrawn from the study.Patients achieving PR or CR at the end of induction will proceed to the maintenance phase (Cycles 7-24).Patients with SD or PD at the end of induction will be withdrawn from the study. Maintenance Phase (18 cycles, 28 days per cycle)： Orelabrutinib + Obinutuzumab \+ Venetoclax

Drug: Orelabrutinib; Drug: Obinutuzumab; Drug: Venetoclax

Interventions

Orelabrutinib DRUG

Orelabrutinib: 150 mg, d1-d28, C1-C6 (Induction Phase ) ; 150 mg, d1-d28, C7-C24 (Maintenance Phase)

orelabrutinib (O) combined with obinutuzumab (G) and short-course venetoclax (V)

Obinutuzumab DRUG

Obinutuzumab: 1000 mg/m², on d1, d8, and d15 in C1; and on d1 in C2-C6 (Induction Phase ) ; 1000 mg/m², d1, once every 2 cycles, C7-C24 (Maintenance Phase)

orelabrutinib (O) combined with obinutuzumab (G) and short-course venetoclax (V)

Venetoclax DRUG

Venetoclax: dose ramp-up in C2 (20 mg → 400 mg); 400 mg on d1-d14 in C3-C6(Induction Phase ) ; 400 mg, d1-d14, C7-C24(Maintenance Phase)

orelabrutinib (O) combined with obinutuzumab (G) and short-course venetoclax (V)

Eligibility Criteria

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

You may qualify if:

• Voluntarily participate and sign the informed consent form;
• Age ≥ 18 years, male or female;
• Life expectancy ≥ 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Patients with ECOG 3 may be enrolled only if the decline in performance status is attributed to the underlying disease and the investigator determines that they may benefit from the treatment;
• Pathologically confirmed diagnosis of mantle cell lymphoma (MCL) and treatment-naïve;
• Presence of measurable and/or evaluable lymphoma lesions;
• Adequate bone marrow reserve, defined as: absolute neutrophil count \> 1.0×10⁹/L or platelet count \> 75×10⁹/L, unless cytopenias are considered to be related to bone marrow involvement by lymphoma and deemed recoverable by the investigator;
• Hepatic function: AST (SGOT) and ALT (SGPT) ≤ 2.5 × upper limit of normal (ULN) (in the absence of liver involvement) or ≤ 5 × ULN (in the presence of liver involvement); total bilirubin (TBIL) ≤ ULN; serum creatinine (CRE) ≤ 1.5 × ULN;
• Creatinine clearance ≥ 30 mL/min, calculated using the Cockcroft-Gault formula;
• Able to comply with the study visit schedule and other protocol requirements;
• All patients of childbearing potential must agree to use effective contraceptive measures during the study and for 24 months after study treatment discontinuation. Female patients of childbearing potential must have a negative urine pregnancy test prior to the first dose of study treatment.

You may not qualify if:

• Received prior treatment for lymphoma within 2 weeks before study enrollment;
• Any serious medical condition, including but not limited to:
• Uncontrolled hypertension (defined as blood pressure that remains uncontrolled after at least 4 weeks of treatment with a reasonable and tolerable regimen of 3 or more antihypertensive agents \[including diuretics\] at adequate doses, or requiring 4 or more antihypertensive agents to achieve adequate control);
• Uncontrolled congestive heart failure within 6 months prior to screening (New York Heart Association \[NYHA\] Class III \[moderate\] or Class IV \[severe\] cardiac disease);
• Left ventricular ejection fraction (LVEF) \< 50%;
• Symptomatic coronary artery disease (e.g., chest tightness, chest pain, palpitations, fatigue) or coronary artery disease requiring medical therapy; ⑤Severe bradycardia (heart rate \< 40 beats per minute \[bpm\]) with hypotension, dizziness, or syncope; patients with a history of arrhythmia should undergo cardiac evaluation;
• Known active bacterial, viral, fungal, or other infection (excluding fungal infection of the nail bed), or major infection within 2 weeks prior to the first dose of study drug;
• Moderate to severe hepatic impairment (Child-Pugh Class B or C); ⑧Active bleeding within 2 months prior to screening, or clear evidence of bleeding diathesis as judged by the investigator; ⑨Current pulmonary disease that impairs lung function, such as pulmonary fibrosis or drug-related pneumonitis, which is deemed intolerable by the investigator; ⑩Any psychiatric or cognitive disorder that may limit the patient's ability to understand, execute, or comply with the informed consent and study requirements;
• Known active hepatitis C virus (HCV) infection; or other acquired or congenital immunodeficiency disorders, including but not limited to human immunodeficiency virus (HIV) infection;
• All patients with central nervous system (CNS) involvement by lymphoma;
• Diagnosis of or receiving treatment for another malignancy other than lymphoma, except for the following:
• ①Malignancy that has been treated with curative intent and with no known active disease for ≥ 5 years prior to enrollment;
• ②Adequately treated basal cell carcinoma of the skin (excluding melanoma) with no evidence of disease;
• ③Adequately treated carcinoma in situ of the cervix with no evidence of disease;
• Known hypersensitivity to any study drug;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (2)

Changzhou Second People's Hospital

Changzhou, Jiangsu, China

RECRUITING

Jiangsu province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

orelabrutinib; obinutuzumab; venetoclax

Condition Hierarchy (Ancestors)

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

Study Officials

• Yi Xia

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi Xia

CONTACT

+8613770698391; cynthia0311@163.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: July 17, 2026
• First Posted: July 22, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: July 22, 2026

Record last verified: 2026-07

Locations

CN (2)