Zanubrutinib and Rituximab Followed by R-DHAOx Then Maintenance With Zanubrutinib for Newly-Diagnosed MCL

Mantle Cell Lymphoma Clinical Trial

Official title:

Zanubrutinib and Rituximab Followed by R-DHAOx (Rituximab, Dexamethasone, Cytarabine and Oxaliplatin) Regimen Then Maintenance With Zanubrutinib for Newly-Diagnosed Mantle Cell Lymphoma (MCL): a Single Arm, Open Label, Multi-center Phase II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04624958
• Other study ID #: B2020-232-01
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2020
• Est. completion date: December 2025

Study information

• Verified date: May 2022
• Source: Sun Yat-sen University
• Contact: Qingqing Cai, MD
• Phone: 0086-20-87342823
• Email: caiqq[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase 2 trial studies the efficacy and safety of zanubrutinib plus rituximab followed by R-DHAOx (rituximab, dexamethasone, cytarabine and oxaliplatin) regimen then maintenance with zanubrutinib for newly-diagnosed Mantle Cell Lymphoma (MCL).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed CD20 positive mantle cell lymphoma;

• Patients with MCL-related symptomatic and need immediate therapy; Include any of the following: (1) Blastoid variant (2) Pleomorphic variant (3) Ki-67 =30% (4) Bulky mass > 7 cm or =2 tumors, each =5 cm in diameter (5) Mutations in TP53, c-MYC or NOTCH genes (6) Size of spleen =20 cm (7) Lymphoma B symptoms (8) Mantle Cell International Prognostic Score (MIPI) > 3 (9) Lymphoma threatening organ function (10) Elevated lactate dehydrogenase (11) Peripheral blood white blood cell > 50×10^9/L (12) Pancytopenia due to bone marrow involvement (13) Pain due to lymphoma;

• Patients received no prior anti-lymphoma treatment;

• At least one evaluable lesion according to 2014 Lugano criteria;

• Ann Arbor stage II-IV;

• Eastern Cooperative Oncology Group (ECOG) of 0-2;

• Life expectancy > 3 months;

• Able to participate in all required study procedures;

• Proper functioning of the major organs: 1) The absolute value of neutrophils (>1.5×10^9/L); 2) platelet count (> 75×10^9/L); 3) Hemoglobin (> 80 g/L); 4) Serum creatinine <1.5 times Upper Limit Normal (ULN) ; 5) Serum total bilirubin < 1.5 times ULN; 6) Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) < 2.5 times ULN; 7) Coagulation function: International Normalized Ratio (INR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) < 1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are within the expected range at screening time);

Exclusion Criteria:

• Involvement of central nervous system (CNS)

• Patients with Hemophagocytic syndrome;

• Patients with active bleeding, bleeding tendency or require anticoagulation treatment;

• Patients require treatment with strong CYP3A inhibitors;

• Uncontrolled active infection, with the exception of tumor-related B symptom fever;

• History of human immunodeficiency virus (HIV) infection and/or patients with acquired immunodeficiency syndrome are known;

• Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA (no more than 1000 IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 1000 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group;

• Diagnosed with or receiving treatment for malignancy other than lymphoma;

• Pregnant or breastfeeding women;

• Other researchers consider it unsuitable for patients to participate in this study.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Newly-diagnosed Mantle Cell Lymphoma

Intervention

Drug:
• Zanubrutinib and Rituximab
Zanubrutinb 160mg PO BID d1-28; Rituximab 375mg/m2 iv.drip d1.
• R-DHAOx
Rituximab 375mg/m2 iv.drip d1; Dexamethasone 20mg iv.drip d1-4; Cytarabine 2000mg/m2 (1000mg/m2 for patients aged over 65) iv.drip d2,3 Oxaliplatin 130mg/m2 iv.drip d1.
• Zanubrutinib Maintenance
Zanubrutinb 160mg PO BID.

Locations

Country	Name	City	State
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission rate after PART A	Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.	3 years
Secondary	Complete remission rate after study treatment	Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.	3 years
Secondary	Objective Response rate	Objective Response rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.	3 years
Secondary	Progression Free Survival	The time from the start of treatment to the progression of the tumor or death (due to any cause).	5 years
Secondary	Overall Survival	The time from the start of treatment to time of death (due to any cause).	5 years
Secondary	Time to Response	The time from the start of treatment to the first assessment of complete remission or partial remission.	3 years
Secondary	Duration of Response	The time from the first assessment of complete remission or partial remission to progressive disease or death (due to any cause).	5 years
Secondary	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	3 years