Trial Title:
Obinutuzumab, Zanubrutinib, and Lenalidomide Followed Short-Cycle of Obinutuzumab and Cytarabine in Newly Diagnosed Mantle Cell Lymphoma
NCT ID:
NCT06504199
Condition:
Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Cytarabine
Lenalidomide
Obinutuzumab
Zanubrutinib
Conditions: Keywords:
newly diagnosed
Mantle Cell Lymphoma
ZGR
Short-Cycle Cytarabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Obinutuzumab
Description:
No dose adjustment of Obinutuzumab is allowed.
Arm group label:
ZGR followed short cycle of Obinutuzumab and Cytarabine
Intervention type:
Drug
Intervention name:
Zanubrutinib
Description:
Zanubrutinib was allowed to be titrated to 80 mg bid or 80 mg qd
Arm group label:
ZGR followed short cycle of Obinutuzumab and Cytarabine
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Lenalidomide was allowed to be titrated to 15 mg/day (induction phase) or 5 mg/day
(maintenance phase).
Arm group label:
ZGR followed short cycle of Obinutuzumab and Cytarabine
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
The specific dose is determined by the investigator according to the actual situation of
the patient.
Arm group label:
ZGR followed short cycle of Obinutuzumab and Cytarabine
Intervention type:
Biological
Intervention name:
CAR-T
Description:
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.
Arm group label:
ZGR followed short cycle of Obinutuzumab and Cytarabine
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Institute of Hematology & Blood Diseases Hospital
Address:
City:
Tianjin
Zip:
300020
Country:
China
Status:
Recruiting
Contact:
Last name:
Shuhua Yi, Dr.
Phone:
86-022-23909106
Email:
yishuhua@ihcams.ac.cn
Contact backup:
Last name:
Lugui Qiu, Dr.
Phone:
86-022-23909286
Email:
qiulg@ihcams.ac.cn
Facility:
Name:
Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
Address:
City:
Tianjin
Zip:
300020
Country:
China
Status:
Recruiting
Contact:
Last name:
Yuting Yan
Start date:
July 18, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
Institute of Hematology & Blood Diseases Hospital, China
Agency class:
Other
Source:
Institute of Hematology & Blood Diseases Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06504199
