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

NCT ID: NCT06504199

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-18
• Study Completion Date: 2028-12-31

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.

Detailed Description

Based on the clinical need for first-line treatment of MCL, this study proposed to enroll 39 patients with MCL who have not previously received any systemic therapy for MCL. All patients were treated with ZGR regimen for 6 cycles after enrollment, followed by 3 cycles of Obinutuzumab + cytarabine in 28-day cycles. For non-high-risk patients, lenalidomide and Zanubrutinib were used for maintenance; high-risk patients continued Lenalidomide and Zanubrutinib for maintenance following CAR-T cell therapy for 1 year for Lenalidomide and 2 years for Zanubrutinib. The primary endpoint of CRR and secondary endpoints (including ORR, PFS, DoR, and OS) were followed and recorded to explore the efficacy and safety of ZGR followed by a short cycle of Obinutuzumab and cytarabine induction therapy in treatment-naive MCL.

Conditions

Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ZGR followed short cycle of Obinutuzumab and Cytarabine

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.

Group Type: EXPERIMENTAL

Obinutuzumab

Intervention Type: DRUG

No dose adjustment of Obinutuzumab is allowed.

Zanubrutinib

Intervention Type: DRUG

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

Lenalidomide

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

CAR-T

Intervention Type: 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.

Interventions

Obinutuzumab

No dose adjustment of Obinutuzumab is allowed.

Intervention Type: DRUG

Zanubrutinib

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

Intervention Type: DRUG

Lenalidomide

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

Intervention Type: DRUG

Cytarabine

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

Intervention Type: DRUG

CAR-T

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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shuhua Yi

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital, China

Locations

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

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

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Shuhua Yi

Role: CONTACT

yishuhua@ihcams.ac.cn

+86-022-23909106

Lugui Qiu

Role: CONTACT

qiulg@ihcams.ac.cn

+86-022-23909172

Facility Contacts

Shuhua Yi, Dr.

Role: primary

yishuhua@ihcams.ac.cn

86-022-23909106

Lugui Qiu, Dr.

Role: backup

qiulg@ihcams.ac.cn

86-022-23909286

Yuting Yan

Role: primary

Other Identifiers

IIT2024010

Identifier Type: -

Identifier Source: org_study_id