Obinutuzumab, Zanubrutinib, and Lenalidomide Followed Short-Cycle of Obinutuzumab and Cytarabine in Newly Diagnosed Mantle Cell Lymphoma

NCT06504199 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IIT2024010
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to preliminarily explore the efficacy and safety of the combination of Obinutuzumab and Zanubrutinib plus Lenalidomide (ZGR) followed by a short cycle of cytarabine and Obinutuzumab in the induction treatment of newly diagnosed mantle cell lymphoma (MCL) . The investigators propose ZGR followed by a short cycle of Obinutuzumab and cytarabine could be an effective first-line treatment for MCL.

Conditions

Mantle Cell Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  defined as the proportion of patients with complete response as assessed by response to induction therapy using the 2014 Lugano criteria.

  up to the end of 9 cycles of treatment(each cycle is 28 days)

Secondary Outcomes (5)

• overall response rate (ORR)

  up to the end of 9 cycles of treatment(each cycle is 28 days)

• Minimal residual disease (MRD) negative rate of

  up to the end of 9 cycles of treatment(each cycle is 28 days)

• Progress-free survival (PFS)

  up to 5 years

• Duration of tumor remission (DoR)

  up to 5 years

• Overall survival (OS)

  up to 5 years

Study Arms (1)

ZGR followed short cycle of Obinutuzumab and Cytarabine

EXPERIMENTAL

All patients were treated with ZGR regimen for 6 cycles after enrollment, followed by 3 cycles of Obinutuzumab and Cytarabine in 28-day cycles. Obinutuzumab: 1000 mg, intravenous drip, administered on d1, d8 and d15 of the first cycle, and administered on the first day of each cycle starting from the second cycle. Zanubrutinib: 160 mg, bid, continuous oral. Lenalidomide: 20 mg/d, qd, oral, d1-d21.Cytarabine: for young tolerable patients, the dose is 2 g/m2, q12h, intravenous drip, d1-2ND for elderly/intolerant patients, the dose is 500 mg/m2, q12h, intravenous drip, completed 2-3 hours, d1-3. The specific dose is determined by the investigator according to the actual situation of the patient. Zanubrutinib for 2 years combination with Lenalidomide for 1 year was used for maintenance treatment in non-high-risk patients and in high-risk patients after recovery of hemogram 2 months after CAR-T.

Drug: Obinutuzumab; Drug: Zanubrutinib; Drug: Lenalidomide; Drug: Cytarabine; Biological: CAR-T

Interventions

Obinutuzumab DRUG

No dose adjustment of Obinutuzumab is allowed.

ZGR followed short cycle of Obinutuzumab and Cytarabine

Zanubrutinib DRUG

Zanubrutinib was allowed to be titrated to 80 mg bid or 80 mg qd

ZGR followed short cycle of Obinutuzumab and Cytarabine

Lenalidomide DRUG

Lenalidomide was allowed to be titrated to 15 mg/day (induction phase) or 5 mg/day (maintenance phase).

ZGR followed short cycle of Obinutuzumab and Cytarabine

Cytarabine DRUG

The specific dose is determined by the investigator according to the actual situation of the patient.

ZGR followed short cycle of Obinutuzumab and Cytarabine

CAR-T BIOLOGICAL

zanubrutinib in combination with lenalidomide was allowed for maintenance treatment in high-risk patients for 1 year and zanubrutinib for 2 years after recovery of hemogram 2 months after CAR-T. High-risk Patients with any of the following conditions: Mantle cell lymphoma International Prognostic Index (MIPI-c) high-risk, blastic/pleomorphic type, TP53 mutation/deletion, CDKN2A deletion, MYC amplification/translocation, or incomplete response at induction stage; Non-high-risk group: no high-risk features.

ZGR followed short cycle of Obinutuzumab and Cytarabine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 80 years, male or female;
• Patients with pathologically (histologically or cytologically) confirmed MCL and at least one measurable lesion by Lugano criteria;
• No prior systemic therapy for MCL;
• Eastern Cooperative Oncology Group (ECOG) score of 0-2 points;
• 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%;
• 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;
• The subjects voluntarily participate in the study and sign the informed consent form. They have good compliance and cooperate in the follow-up.

You may not qualify if:

• Known central nervous system disease such as brain or meninges, including central nervous system lymphoma.
• Congestive heart failure, Class III or IV (New York Heart Association, NYHA);
• 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)
• Previous use of investigational drugs;
• Any active systemic viral, bacterial, or fungal infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study drug;
• 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
• Allergic reactions, anaphylactic reactions and adverse drug reactions
• Severe allergic reactions to other monoclonal antibodies;
• Allergy or intolerance to infusion;
• Patients with a history of serious allergy to the investigational drug or its preventive medication;
• Physical examination and laboratory findings
• 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;
• Pregnant or lactating women; patients with fertility are unwilling or unable to take effective contraceptive measures;
• Known history of positive human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS);
• 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;

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (2)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

Location

Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

obinutuzumab; zanubrutinib; Lenalidomide; Cytarabine

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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Shuhua Yi

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: reated with 6 cycles of ZGR followed by a short cycle (3 cycles) of cytarabine + Obinutuzumab induction therapy. The maintenance regimen was selected according to patient risk stratification. Zanubrutinib in combination with lenalidomide was used for maintenance treatment in non-high-risk patients; maintenance treatment with zanubrutinib in combination with lenalidomide was allowed in high-risk patients after recovery of hemogram 2 months after treatment with chimeric antigen receptor T cells (CAR-T), with lenalidomide maintained for 1 year and zanubrutinib maintained for 2 years.

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 16, 2024
• Study Start: July 18, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)