Clinical trial NCT04624958: Zanubrutinib and Rituximab Followed by R-DHAOx Then Maintenance with Zanubrutinib for Newly-Diagnosed MCL
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Newly-diagnosed Mantle Cell Lymphoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2020-11-12
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Complete remission rate after PART A
timeFrame: 3 years
Secondary outcomes:
measure: Complete remission rate after study treatment
timeFrame: 3 years
measure: Objective Response rate
timeFrame: 3 years
measure: Progression Free Survival
timeFrame: 5 years
measure: Overall Survival
timeFrame: 5 years
measure: Time to Response
timeFrame: 3 years
measure: Duration of Response
timeFrame: 5 years
measure: Percentage of Participants With Adverse Events
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Qingqing Cai, MD
role: PRINCIPAL_INVESTIGATOR
References: