This is a Phase II, Open-label, Multicentre Study of Zanubrutinib-containing Regimens in Patients With Newly Diagnosed Mantle Cell Lymphoma

A Study of the Zanubrutinib-containing Regimens in Patients With Newly Diagnosed Mantle Cell Lymphoma

This is a phase II, open-label, multicentre study of Zanubrutinib-containing regimens in patients with newly diagnosed mantle cell lymphoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell
• Intervention / Treatment: Drug: Zanubrutinib,Obinutuzumab; Drug: Zanubrutinib and R-BAC

Detailed Description

This study is a prospective, multicenter, investigator-initiated clinical trial to evaluate the efficacy and safety of zanubrutinib-containing regimens in the treatment of newly diagnosed elderly or young patients with high risk MCL, aiming to find a more optimal treatment regimen for elderly or young patients with high risk MCL to improve the efficacy, survival time and quality of life of patients.

In elderly patients arm：patients start with the induction therapy of zanubrutinib combined with obinutuzumab for 1 year and then entered the maintenance therapy of zanubrutinib orally until intolerable toxicity or disease progression

In young patients with high risk arm：patiens <65 years，and meet one or more of the following risk factors: TP53 mutation, blastoid/pleomorphic type, high sMIPI score. patients start with 6 cycles of induction therapy with zanubrutinib combined with R-BAC regimen, and the patients who achieve CR/PR and meet the transplantation criteria will receive ASCT consolidationand, then received maintenance therapy with zanubrutinib. otherwise, Patients who is ineligible for transplantation，will take zanubrutinib orally until intolerable toxicity or disease progression.

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: keshu Zhou; Phone Number: 0371-65587306; Email: drzhouks77@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary participation in clinical study; Fully understand and understand the study and sign the informed consent form (ICF);Willingness to follow and ability to complete all study steps
2. Histopathologically confirmed mantle cell lymphoma according to the 5th edition of the World Health Organization (WHO)，previous untreatment for mantle-cell lymphoma (MCL)
3. The elderly group ≥65 years old;The young group was ≥18 years old and < 65 years old.
4. ECOG Performance Status 0-3
5. Life expectancy of at least 3 months
6. At least one evaluable lesion according to 2014 Lugano criteria;
7. Proper functioning of the major organs, no major heart, lung, liver, kidney, or immunodeficiency (no blood transfusion, granulocyte colony-stimulating factor, or other medical support within 7 days before starting the study) :Hemoglobin (HB)≥60 g/L;Absolute neutrophil count(ANC)≥0.5×10^9/L;Platelet count（PLT）≥50×10^9/L;AST and ALT ≤ 2.5 x ULN；Total bilirubin ≤ 1.5 times the ULN;Ccr≥40ml/min（Cockcroft-Gault ）；Left Ventricular Ejection Fraction (LVEF) ≥ 50%

Exclusion Criteria:

1. The presence of other tumors could affect the study medication or interfere with the results;
2. Patients require treatment with strong or moderate CYP3A inhibitors;
3. Pregnant or lactating women;
4. Known to be allergic to the test drug ingredients;
5. Subjects of childbearing potential who are unwilling to use highly effective contraceptive methods;
6. Live vaccination was administered within 28 days prior to treatment
7. Known human immunodeficiency virus (HIV) infection or suggested active B or C infection The following serologic status of hepatitis C virus infection: 1) Hepatitis B virus (HBV) DNA positive. Positive hepatitis B surface antigen (HBsAg) or anti-hepatitis B core antibody (HBcAb) seropositive if HBV DNA is undetectable and willing to accept Monthly surveillance for HBV reactivation was eligible. 2) Hepatitis C virus (HCV) antibody positive. For patients with HCV antibodies present, if undetectable HCV RNA, can be included;
8. Severe coagulopathy and serious impairment of heart, brain, lung, liver, kidney and other organs
9. History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months;
10. Any risk that is considered by the investigator to be likely to affect the safety of the subjects or to pose a risk to the study And vital diseases, medical conditions, or organ system insufficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elder Patients（≥65）; Induction: Zanubrutinib and Obinutuzumab 1year Maintenance: Zanubrutinib continued until progression	Drug: Zanubrutinib,Obinutuzumab; Zanubrutinib, 160mg PO BID. C1D17 continuously for 1 year or until progressive disease； Obinutuzumab ：Obinutuzumab will be administered 1,000 mg intravenously on days 1, 8, and 15 of cycle 1, then 1,000 mg on day 1 of cycles 2 to 6, then 1,000 mg every 8 weeks，up to 20 doses. 1 cycle = 28 days. Maintenance: Zanubrutinib, 160mg PO BID
Experimental: Young Patients with High risk （≥18，<65）; Induction: Zanubrutinib and R-BAC 6 cycles Consolidation: ASCT（If eligible for transplantation），Otherwise, the patient was directly entered into maintenance treatment Maintenance: Zanubrutinib continued until progression	Drug: Zanubrutinib and R-BAC; Induction: Zanubrutinib and R-BAC 6 cycles Consolidation: ASCT（If eligible for transplantation），Otherwise, the patient was directly entered into maintenance treatment Maintenance: Zanubrutinib continued until progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response rate after induction	Objective Response rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.	3 yeas

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	Adverse Events will be determined and graded on the basis of investigator assessments according to NCI CTC AE 5.0	5 years
Complete remission rate after Interim treatment	Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.	3 years
MRD negativity rate after induction	MRD negativity rate after induction treatment	3 years
Progression free survival (PFS)	The time from start of treatment to progression or death from any cause	5 years
Overall survival (OS)	The time from start of treatment to death from any cause	5 years

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: May 19, 2024
• First Submitted That Met QC Criteria: May 19, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Zanubrutinib
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Obinutuzumab; Zanubrutinib
• Other Study ID Numbers: IIT-TN MCL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No