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

NCT ID: NCT04624958

Last Updated: 2024-10-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2026-12-31

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).

Conditions

Mantle Cell Lymphoma; Newly-diagnosed Mantle Cell Lymphoma

Study Design

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

Study Groups

zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance

Part A (Zanubrutinib and Rituximab): Patients receive zanubrutinib on days 1-28 and rituximab on day 1. Treatment cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or until patients achieve CR.

PART B (Consolidation chemotherapy of R-DHAOx): Patients receive R-DHAOx regimen every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Elderly patients (> 65 years old) and patients who achieved CR and minimal residual disease negative after PART B receive zanubrutinb maintenance therapy. Young patients (<65 years old) who achieved CR but minimal residual disease positive after PART B can receive autologous stem cell transplantation and then zanubrutinb maintenance therapy. Patients with PD, SD or PR after PART B quit the trial.

ZANUBRUTINB MAINTENANCE: Patients receive zanubrutinib every day for up to one year.

Group Type: EXPERIMENTAL

Zanubrutinib and Rituximab

Intervention Type: DRUG

Zanubrutinb 160mg PO BID d1-28; Rituximab 375mg/m2 iv.drip d1.

R-DHAOx

Intervention Type: DRUG

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

Intervention Type: DRUG

Zanubrutinb 160mg PO BID.

Interventions

Zanubrutinib and Rituximab

Zanubrutinb 160mg PO BID d1-28; Rituximab 375mg/m2 iv.drip d1.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Zanubrutinib Maintenance

Zanubrutinb 160mg PO BID.

Intervention Type: DRUG

Other Intervention Names

PART A; PART B

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Qingqing Cai

Chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qingqing Cai, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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, China

Countries

China

Other Identifiers

B2020-232-01

Identifier Type: -

Identifier Source: org_study_id