Combination treatment for newly diagnosed mantle cell lymphoma

A Prospective, Open-Label, Single-Arm Study of Obinutuzumab, Zanubrutinib, and Lenalidomide Followed Short-Cycle Cytarabine in First-Line Treatment of Mantle Cell Lymphoma

This study is testing a new combination treatment for people with newly diagnosed mantle cell lymphoma to see if it helps them respond better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: prednisone, Obinutuzumab, Zanubrutinib, CAR-T
• Locations: 2 sites (Tianjin, Tianjin and 1 other locations)
• Trial ID: NCT06504199 on ClinicalTrials.gov

What this trial studies

This study explores the efficacy and safety of a treatment regimen combining Obinutuzumab, Zanubrutinib, and Lenalidomide, followed by a short cycle of cytarabine and Obinutuzumab, for patients with newly diagnosed mantle cell lymphoma (MCL). A total of 39 patients who have not received prior systemic therapy for MCL will be enrolled and treated with the ZGR regimen for six cycles, followed by three cycles of Obinutuzumab and cytarabine. The study aims to evaluate the complete response rate as the primary endpoint, along with other secondary endpoints such as overall response rate and progression-free survival. This approach seeks to provide an effective first-line treatment option for MCL.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with pathologically confirmed mantle cell lymphoma and no prior systemic therapy.

Not a fit: Patients with prior systemic therapy for mantle cell lymphoma or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective first-line therapy for patients with newly diagnosed mantle cell lymphoma.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in treating other forms of lymphoma with combination therapies.

Eligibility criteria

Inclusion Criteria:

1. Aged 18 to 80 years, male or female;
2. Patients with pathologically (histologically or cytologically) confirmed MCL and at least one measurable lesion by Lugano criteria;
3. No prior systemic therapy for MCL;
4. Eastern Cooperative Oncology Group (ECOG) score of 0-2 points;
5. Normal function of vital organs, i.e. meeting the following criteria:

   a) Blood routine examination must be in accordance with (no blood transfusion, no use of hematopoietic factors and no use of drugs for correction within 14 days): i. Absolute neutrophil count (ANC) ≥ 1 × 10＾9/L; ii. Platelet count (PLT) ≥ 75 × 10＾9/L; b) Chemistry panel must meet the following criteria: i. Total bilirubin (TBIL) ≤ 2.0 × upper limit of normal (ULN); ii. Glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) ≤ 2.0 × ULN iii. Creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula); c) Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%;
6. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to the start of study medication and are willing to use a medically recognized highly effective contraceptive method (e.g., intrauterine device, contraceptive pill, or condom) during the study and within 6 months after the last dose of study drug; male subjects with partners of childbearing potential should be surgically sterile or agree to use an effective method of contraception during the study and within 6 months after the last dose of study drug;
7. The subjects voluntarily participate in the study and sign the informed consent form. They have good compliance and cooperate in the follow-up.

Exclusion Criteria:

1. Known central nervous system disease such as brain or meninges, including central nervous system lymphoma.
2. Congestive heart failure, Class III or IV (New York Heart Association, NYHA);
3. Other primary malignancies within the last 3 years (except non-melanoma skin cancer, curatively treated localized prostate cancer, carcinoma in situ of the cervix, or squamous epithelial endothelial lesions on PAP smear)
4. Previous use of investigational drugs;
5. Any active systemic viral, bacterial, or fungal infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study drug;
6. Use of immunosuppressive agents, excluding nasal sprays and inhaled corticosteroids or physiological doses of systemic steroids (i.e., no more than 20 mg/day prednisone or its equivalent) within 7 days prior to the first dose of study drug
7. Allergic reactions, anaphylactic reactions and adverse drug reactions

   1. Severe allergic reactions to other monoclonal antibodies;
   2. Allergy or intolerance to infusion;
   3. Patients with a history of serious allergy to the investigational drug or its preventive medication;
8. Physical examination and laboratory findings

   1. Patients with congenital or acquired immunodeficiency, such as active hepatitis B virus (HBV DNA ≥ 500 IU/mL), hepatitis C (hepatitis C antibody positive, and HCV-RNA higher than the lower limit of detection of the analytical method) or combined hepatitis B and C co-infection;
   2. Pregnant or lactating women; patients with fertility are unwilling or unable to take effective contraceptive measures;
   3. Known history of positive human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS);
9. Any condition that, in the opinion of the investigator, may jeopardize the subject or may render the subject unable to meet or perform the study requirements;
10. Other conditions that the investigator considers inappropriate for entry into this study.

Where this trial is running

Tianjin, Tianjin and 1 other locations

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

Study contacts

• Principal investigator: Shuhua Yi — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Shuhua Yi

Conditions Mantle Cell Lymphoma; newly diagnosed; ZGR; Short-Cycle Cytarabine