Obinutuzumab plus zanubrutinib and lenalidomide as first treatment for mantle cell lymphoma

Obinutuzumab, Zanubrutinib, and Lenalidomide as First-Line Therapy for Mantle Cell Lymphoma: A Prospective, Single-Arm, Open-Label, Multicenter Study

This trial will test whether a combination of obinutuzumab, zanubrutinib, and lenalidomide (with CAR‑T offered for high‑risk patients) works as a first‑line option for people newly diagnosed with mantle cell lymphoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: prednisone, zanubrutinib, CAR-T
• Locations: 2 sites (Tianjin, Tianjin Municipality and 1 other locations)
• Trial ID: NCT07261163 on ClinicalTrials.gov

What this trial studies

This is a prospective, open‑label, single‑arm phase 2 study enrolling adults with previously untreated mantle cell lymphoma who have measurable disease. All participants receive a ZGR induction regimen combining obinutuzumab, zanubrutinib, and lenalidomide. After induction, patients are stratified by risk: non‑high‑risk patients receive lenalidomide for one year and zanubrutinib for two years as maintenance, while high‑risk patients proceed to CAR‑T cell therapy followed by the same maintenance. The primary aim is to determine feasibility and preliminary efficacy of this risk‑adapted, largely chemo‑free first‑line approach.

Who should consider this trial

Good fit: Adults aged 18–80 with histologically confirmed, previously untreated mantle cell lymphoma, at least one measurable lesion, ECOG performance status 0–2, and adequate hematologic, hepatic/renal, and cardiac function are the intended participants.

Not a fit: Patients who have received prior systemic therapy for MCL, have inadequate organ or cardiac function, significant cytopenias, or who cannot access the Tianjin study center are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could produce deeper and longer remissions using a chemo‑free induction and targeted CAR‑T for those with high‑risk disease.

How similar studies have performed: Individual components—BTK inhibitors, anti‑CD20 antibodies, lenalidomide combinations, and CAR‑T therapy—have shown activity in MCL, but this specific chemo‑free, risk‑adapted first‑line combination is novel and not yet validated in randomized trials.

Eligibility criteria

Inclusion Criteria:

1. Age between 18 and 80 years inclusive, both genders are eligible.
2. Histologically or cytologically confirmed diagnosis of Mantle Cell Lymphoma (MCL), with at least one measurable lesion according to Lugano criteria.
3. No prior systemic therapy for MCL.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Adequate organ function, defined as:

   1. Hematologic function (without red blood cell or platelet transfusion, growth factor support, or medication correction within 14 days prior to enrollment):Absolute neutrophil count (ANC) ≥ 1 × 10⁹/L;Platelet count (PLT) ≥ 75 × 10⁹/L;
   2. Biochemical tests must meet the following criteria::

      Total bilirubin ≤ 2.0 × upper limit of normal (ULN);Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 × ULN;Creatinine clearance ≥ 30 mL/min, calculated by the Cockcroft-Gault formula;
   3. Cardiac function:Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram.
6. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of study treatment, and must agree to use a highly effective method of contraception (e.g., intrauterine device, hormonal contraception, or condom use) during the study and for 6 months after the last dose of study drug. Male subjects whose partners are of childbearing potential must be surgically sterile or agree to use effective contraception during the study and for 6 months after the last dose of study drug.
7. Willing and able to provide written informed consent and comply with the study follow-up requirements.

Exclusion Criteria:

1. Known central nervous system (CNS) involvement, including brain or meningeal lymphoma.
2. Congestive heart failure with New York Heart Association (NYHA) Class III or IV cardiac dysfunction.
3. History of other primary malignancies within the past 3 years, except for non-melanoma skin cancer, localized prostate cancer considered cured, cervical in situ carcinoma, or squamous intraepithelial lesion detected by PAP smear.
4. Prior treatment with investigational drugs.
5. Active systemic viral, bacterial, or fungal infection requiring antimicrobial therapy within 2 weeks prior to first administration of study drug.
6. Use of immunosuppressive agents within 7 days prior to first administration of study drug, except for intranasal or inhaled corticosteroids, or systemic corticosteroids at physiologic doses (i.e., ≤ 20 mg/day prednisone or equivalent).
7. History of hypersensitivity, allergic reactions, or adverse drug reactions:Severe hypersensitivity reaction to monoclonal antibodies;Allergy or intolerance to infusions;History of severe allergy to study drugs or premedication agents.
8. Physical or laboratory findings:Congenital or acquired immunodeficiency, such as active hepatitis B (HBV DNA ≥ 500 IU/mL), hepatitis C (positive HCV antibody and HCV-RNA above lower limit of detection), or co-infection with both HBV and HCV; Pregnant or breastfeeding women; subjects of childbearing potential unwilling or unable to use effective contraception; Known history of positive human immunodeficiency virus (HIV) test or acquired immunodeficiency syndrome (AIDS).
9. Any condition that, in the investigator's judgment, may impair subject safety or ability to comply with the study protocol.
10. Other conditions deemed unsuitable for enrollment by the investigator.

Where this trial is running

Tianjin, Tianjin Municipality and 1 other locations

• Institute of Hematology & Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (NOT_YET_RECRUITING)
• Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Shuhua Yi, Doctor

Conditions: Mantle Cell Lymphoma